Objectives. After an injury, the biological reattachment of tendon to bone is a challenge because healing takes place between a soft (tendon) and a hard (bone) tissue. Even after healing, the transition zone in the enthesis is not completely regenerated, making it susceptible to re-injury. In this study, we aimed to regenerate Achilles tendon entheses (ATEs) in wounded rats using a combination of kartogenin (KGN) and platelet-rich plasma (PRP). Methods. Wounds created in rat ATEs were given three different treatments: kartogenin platelet-rich plasma (KGN-PRP); PRP; or saline (control), followed by histological and immunochemical analyses, and mechanical testing of the rat ATEs after three months of healing. Results. Histological analysis showed well organised arrangement of collagen fibres and proteoglycan formation in the wounded ATEs in the KGN-PRP group. Furthermore, immunohistochemical analysis revealed fibrocartilage formation in the KGN-PRP-treated ATEs, evidenced by the presence of both collagen I and II in the healed ATE. Larger positively stained collagen III areas were found in both PRP and saline groups than those in the KGN-PRP group. Chondrocyte-related genes, SOX9 and collagen II, and tenocyte-related genes, collagen I and scleraxis (SCX), were also upregulated by KGN-PRP. Moreover, mechanical testing results showed higher ultimate tensile strength in the KGN-PRP group than in the saline control group. In contrast, PRP treatment appeared to have healed the injured ATE but induced no apparent formation of fibrocartilage. The saline-treated group showed poor healing without fibrocartilage tissue formation in the ATEs. Conclusions. Our results show that injection of KGN-PRP induces fibrocartilage formation in the wounded rat ATEs. Hence, KGN-PRP may be a clinically relevant, biological approach to regenerate injured enthesis effectively. Cite this article: J. Zhang, T. Yuan, N. Zheng, Y. Zhou, M. V. Hogan, J. H-C. Wang. The combined use of kartogenin and platelet-rich plasma promotes fibrocartilage formation in the wounded rat Achilles tendon entheses. Bone Joint Res 2017;6:231–244. DOI: 10.1302/2046-3758.64.BJR-2017-0268.R1

Objectives. This study was conducted to evaluate the cytokine-release kinetics of platelet-rich plasma (PRP) according to different activation protocols. Methods. Two manual preparation procedures (single-spin (SS) at 900 g for five minutes; double-spin (DS) at 900 g for five minutes and then 1500 g for 15 minutes) were performed for each of 14 healthy subjects. Both preparations were tested for platelet activation by one of three activation protocols: no activation, activation with calcium (Ca) only, or calcium with a low dose (50 IU per 1 ml PRP) of thrombin. Each preparation was divided into four aliquots and incubated for one hour, 24 hours, 72 hours, and seven days. The cytokine-release kinetics were evaluated by assessing PDGF, TGF, VEGF, FGF, IL-1, and MMP-9 concentrations with bead-based sandwich immunoassay. Results. The concentration of cytokine released from PRP varied over time and was influenced by various activation protocols. Ca-only activation had a significant effect on the DS PRPs (where the VEGF, FGF, and IL-1 concentrations were sustained) while Ca/thrombin activation had effects on both SS and DS PRPs (where the PDGF and VEGF concentrations were sustained and the TGF and FGF concentrations were short). The IL-1 content showed a significant increase with Ca-only or Ca/thrombin activation while these activations did not increase the MMP-9 concentration. Conclusion. The SS and DS methods differed in their effect on cytokine release, and this effect varied among the cytokines analysed. In addition, low dose of thrombin/calcium activation increased the overall cytokine release of the PRP preparations over seven days, relative to that with a calcium-only supplement or non-activation. Cite this article: Professor J. H. Oh. Cytokine-release kinetics of platelet-rich plasma according to various activation protocols. Bone Joint Res 2016;5:37–45. doi: 10.1302/2046-3758.52.2000540

The use of stem cells transplanted into the intervertebral disc (IVD) is a promising regenerative approach to treat intervertebral disc degeneration (IDD). The aim of this study was to assess the effect of a hydrogel composed of hyaluronic acid (HA) and platelet-rich plasma (PRP) loaded with human mesenchymal stem cells (hMSCs), on IVD extracellular matrix synthesis and nucleus pulposus (NP) marker expression in a whole IVD culture model. HA was blended with batroxobin (BTX), a gelling agent activated in presence of PRP to construct a hydrogel. Bovine IVDs (n=25) were nucleotomised and filled with 1×10. 6. or 2×10. 6. hMSCs suspended in ∼150 mL of the PRP/HA/BTX hydrogel. IVDs harvested at day 0 and nucleotomised IVDs with no hMSCs and/or hydrogel were used as controls. hMSCs alone or encapsulated in the hydrogel were also cultured in well plates to examine the effect of the IVD microenvironment on hMSCs. After 1 week, tissue structure, scaffold integration and gene expression of anabolic (collagen type I, collagen type II and aggrecan), catabolic (matrix metalloproteinase 3 – MMP-3 –, MMP-13 and a disintegrin and metalloproteinase with thrombospondin motifs 4) and NP cell (cytokeratin 19, carbonic anhydrase 12, cluster of differentiation 24) markers were assessed. Histological analysis showed a good integration of the scaffold within the NP area with cell repopulation. At the gene expression level, the hMSC-loaded hydrogels demonstrated to increase disc cell anabolic and catabolic marker expression and promoted hMSC differentiation towards a NP cell phenotype. This study demonstrated that the HA/PRP/BTX may represent a valid carrier for hMSCs being capable of stimulating cell activity and NP marker expression as well as achieving a good integration with the surrounding tissues

The aim of our study was to investigate the effect of platelet-rich plasma on the proliferation and differentiation of rat bone-marrow cells and to determine an optimal platelet concentration in plasma for osseous tissue engineering. Rat bone-marrow cells embedded in different concentrations of platelet-rich plasma gel were cultured for six days. Their potential for proliferation and osteogenic differentiation was analysed. Using a rat limb-lengthening model, the cultured rat bone-marrow cells with platelet-rich plasma of variable concentrations were transplanted into the distraction gap and the quality of the regenerate bone was evaluated radiologically. Cellular proliferation was enhanced in all the platelet-rich plasma groups in a dose-dependent manner. Although no significant differences in the production and mRNA expression of alkaline phosphatase were detected among these groups, mature bone regenerates were more prevalent in the group with the highest concentration of platelets. Our results indicate that a high platelet concentration in the platelet-rich plasma in combination with osteoblastic cells could accelerate the formation of new bone during limb-lengthening procedures

There is good scientific rationale to support the use of growth factors to promote musculoskeletal tissue regeneration. However, the clinical effectiveness of platelet-rich plasma (PRP) and other blood-derived products has yet to be proven. Characterization and reporting of PRP preparation protocols utilized in clinical trials for the treatment of musculoskeletal disease is highly inconsistent, and the majority of studies do not provide sufficient information to allow the protocols to be reproduced. Furthermore, the reporting of blood-derived products in orthopaedics is limited by the multiple PRP classification systems available, which makes comparison of results between studies challenging. Several attempts have been made to characterize and classify PRP; however, no consensus has been reached, and there is lack of a comprehensive and validated classification. In this annotation, we outline existing systems used to classify preparations of PRP, highlighting their advantages and limitations. There remains a need for standardized universal nomenclature to describe biological therapies, as well as a comprehensive and reproducible classification system for autologous blood-derived products. Cite this article: Bone Joint J 2019;101-B:891–896

Aims. The present study investigates the effectiveness of platelet-rich plasma (PRP) gel without adjunct to induce cartilage regeneration in large osteochondral defects in a rabbit model. Methods. A bilateral osteochondral defect was created in the femoral trochlear groove of 14 New Zealand white rabbits. The right knees were filled with PRP gel and the contralateral knees remained untreated and served as control sides. Some animals were killed at week 3 and others at week 12 postoperatively. The joints were harvested and assessed by Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) MRI scoring system, and examined using the International Cartilage Repair Society (ICRS) macroscopic and ICRS histological scoring systems. Additionally, the collagen type II content was evaluated by the immunohistochemical staining. Results. After 12 weeks post-surgery, the defects of the PRP group were repaired by hyaline cartilage-like tissue. However, incomplete cartilage regeneration was observed in the PRP group for three weeks. The control groups showed fibrocartilaginous or fibrous tissue, respectively, at each timepoint. Conclusion. Our study proved that the use of PRP gel without any adjuncts could successfully produce a good healing response and resurface the osteochondral defect with a better quality of cartilage in a rabbit model. Cite this article: Bone Joint Res 2021;10(3):192–202

Aims. Bone marrow-derived mesenchymal stem cells obtained from bone marrow aspirate concentrate (BMAC) with platelet-rich plasma (PRP), has been used as an adjuvant to hip decompression. Early results have shown promise for hip preservation in patients with osteonecrosis (ON) of the femoral head. The purpose of the current study is to examine the mid-term outcome of this treatment in patients with precollapse corticosteroid-induced ON of the femoral head. Methods. In all, 22 patients (35 hips; 11 males and 11 females) with precollapse corticosteroid-induced ON of the femoral head underwent hip decompression combined with BMAC and PRP. Mean age and BMI were 43 years (SD 12) and 31 kg/m² (SD 6), respectively, at the time of surgery. Survivorship free from femoral head collapse and total hip arthroplasty (THA) and risk factors for progression were evaluated at minimum five-years of clinical follow-up with a mean follow-up of seven years (5 to 8). Results. Survivorship free from femoral head collapse and THA for any reason was 84% and 67% at seven years postoperatively, respectively. Risk factors for conversion to THA included a high preoperative modified Kerboul angle (grade 3 or 4) based on preoperative MRI (hazard ratio (HR) 3.96; p = 0.047) and corticosteroid use at the time of decompression (HR 4.15; p = 0.039). The seven-year survivorship for patients with grade 1 or 2 Kerboul angles for conversion to THA for articular collapse, and THA for any reason, were 96% and 72%, respectively, versus THA for articular collapse and THA for any reason in patients with grade 3 or 4 Kerboul angles of 40% (p = 0.003) and 40% (p = 0.032). Conclusion. At seven years, hip decompression augmented with BMAC and PRP provided a 67% survivorship free from THA in patients with corticosteroid-induced ON. Ideal candidates for this procedure are patients with low preoperative Kerboul angles and can stop corticosteroid treatment prior to decompression. Cite this article: Bone Jt Open 2021;2(11):926–931

Platelet-rich plasma (PRP) has been demonstrated to benefit a variety of disciplines. But there exists heterogeneity in results obtained due to lack of standardization of the preparation protocols employed in them. We aim to identify and standardize a preparation protocol for PRP with maximum recovery of platelets to obtain reproducible results across studies. Blood samples were collected from 20 healthy volunteers. The double spin protocol of PRP preparation was analyzed for variables such as centrifugal acceleration, time, and volume of blood processed and final product utilized. The final PRP prepared was investigated for platelet recovery, concentration, integrity, and viability. We noted maximum platelet recovery (86-99%) with a mean concentration factor of 6-times baseline, with double centrifugation protocol at 100xg and 1600xg for 20 minutes each. We also noted that 10 ml of blood in a 15 ml tube was the ideal volume of blood to be processed to maximize platelet recovery. We demonstrated that the lower 1/3rd is the ideal volume to be utilized for clinical application. We did not note a loss of integrity or viability of the platelets in the final product from the above-said protocol. Preparation of PRP by the double spin protocol of 10 ml of blood at 100xg and 1600xg for 20 minutes each in a 15ml tube and using the lower 1/3rd of the final product demonstrated consistent high platelet recovery (86-99%) and concentration (6x) without disturbing the platelet integrity or viability

Objectives. Triamcinolone acetonide (TA) is widely used for the treatment of rotator cuff injury because of its anti-inflammatory properties. However, TA can also produce deleterious effects such as tendon degeneration or rupture. These harmful effects could be prevented by the addition of platelet-rich plasma (PRP), however, the anti-inflammatory and anti-degenerative effects of the combined use of TA and PRP have not yet been made clear. The objective of this study was to determine how the combination of TA and PRP might influence the inflammation and degeneration of the rotator cuff by examining rotator cuff-derived cells induced by interleukin (IL)-1ß. Methods. Rotator cuff-derived cells were seeded under inflammatory stimulation conditions (with serum-free medium with 1 ng/ml IL-1ß for three hours), and then cultured in different media: serum-free (control group), serum-free + TA (0.1mg/ml) (TA group), serum-free + 10% PRP (PRP group), and serum-free + TA (0.1mg/ml) + 10% PRP (TA+PRP group). Cell morphology, cell viability, and expression of inflammatory and degenerative mediators were assessed. Results. Exposure to TA significantly decreased cell viability and changed the cell morphology; these effects were prevented by the simultaneous administration of PRP. Compared with the control group, expression levels of inflammatory genes and reactive oxygen species production were reduced in the TA, PRP, and TA+PRP groups. PRP significantly decreased the expression levels of degenerative marker genes. Conclusions. The combination of TA plus PRP exerts anti-inflammatory and anti-degenerative effects on rotator cuff-derived cells stimulated by IL-1ß. This combination has the potential to relieve the symptoms of rotator cuff injury. Cite this article: T. Muto, T. Kokubu, Y. Mifune, A. Inui, R. Sakata, Y. Harada, F. Takase, M. Kurosaka. Effects of platelet-rich plasma and triamcinolone acetonide on interleukin-1ß-stimulated human rotator cuff-derived cells. Bone Joint Res 2016;5:602–609. DOI: 10.1302/2046-3758.512.2000582

Aims. Platelet-rich plasma (PRP) intra-articular injections may provide a simple and minimally invasive treatment for early-stage knee osteoarthritis (OA). This has led to an increase in its adoption as a treatment for knee OA, although there is uncertainty about its efficacy and benefit. We hypothesized that patients with early-stage symptomatic knee OA who receive multiple PRP injections will have better clinical outcomes than those receiving single PRP or placebo injections. Methods. A double-blinded, randomized placebo-controlled trial was performed with three groups receiving either placebo injections (Normal Saline), one PRP injection followed by two placebo injections, or three PRP injections. Each injection was given one week apart. Outcomes were prospectively collected prior to intervention and then at six weeks, three months, six months, and 12 months post-intervention. Primary outcome measures were Knee Injury and Osteoarthritis Outcome Score (KOOS) and EuroQol five-dimension five-level index (EQ-5D-5L). Secondary outcomes included visual analogue scale for pain and patient subjective assessment of the injections. Results. A total of 102 patients were recruited. The follow-up period was 12 months, at intervals of six weeks, 12 weeks, six months, and 12 months. KOOS-Total significantly improved in all groups at these time intervals compared to pre-injection. There was an improvement in EQ-5D-5L index scores in saline and single injection groups, but not in the multiple injection group. Comparison of treatment groups showed no additional beneficial effect of single or multiple PRP injections above that displayed in the saline injection group. Subjective patient satisfaction and recommendation of treatment received demonstrated a similar pattern in all the groups. There was no indication of superiority of either single or multiple PRP injections compared to saline injections. Conclusion. There is no evidence that single or multiple PRP had any additional beneficial effect compared to saline injection up to 12 months, follow-up after treatment of early stage symptomatic OA of the knee. Cite this article: Bone Joint J 2022;104-B(6):663–671

There are a number of patients in whom hip preservation surgery is not indicated as they have developed signs of early osteoarthritis, and nor can they have a hip replacement as they are too early in the disease process. The use of PRP in OA of the hip has not been studied systematically and this study concisely collates all the available data in the use of PRP in Hip OA. This systematic review and meta-analysis aimed to assess intra-articular platelet-rich plasma as a therapeutic intervention for hip osteoarthritis, including the duration of efficacy, influence of dose and composition of PRP, and the incidence of adverse effects. We performed literature searches on the MEDLINE, EMBASE, CINHAL, WEB OF SCIENCE, COCHRANE and SCOPUS databases, and PRSIMA guidelines were followed. Data was pooled using random effects meta-analysis. We assessed quality of the included studies using the Methodological Index for Non-Randomised Studies (MINORS) instrument, with an additional assessment for Randomised Controlled Trials with the Revised Cochrane risk-of-bias tool for randomized trials (RoB 2). Eight studies were included in the analysis, with data from a total of 331 patients. PRP significantly reduced pain compared to baseline at multiple timepoints, with the greatest effect at 1–2mo follow-up. PRP only significantly improved function at the 1–2mo follow-up. A significantly larger reduction in pain was achieved with a single injection or PRP compared to multiple injections, a total injected dose of PRP <15mL compared to ≥15mL or using a leukocyte-poor PRP preparation compared to leukocyte-rich PRP. There were no lasting adverse effects. Low and moderate quality evidence suggests that PRP reduces pain and improves function at endpoint compared to baseline. Moderate quality evidence suggests a larger reduction in pain is achieved with a single injection of PRP compared to multiple injections, and low quality evidence attributes a larger reduction of pain with a total injected dose of PRP <15mL compared to ≥15mL or using leukocyte-poor PRP compared to leukocyte-rich PRP

We performed this systematic overview on the overlapping meta-analyses that analyzed autologous platelet-rich plasma (PRP) as an adjuvant in the repair of rotator cuff tears and identify the studies which provide the current best evidence on this subject and generate recommendations for the same. We conducted independent and duplicate electronic database searches in PubMed, Web of Science, Scopus, Embase, Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effects on September 8, 2021, to identify meta-analyses that analyzed the efficacy of PRP as an adjuvant in the repair of rotator cuff tears. Methodological quality assessment was made using Oxford Levels of Evidence, AMSTAR scoring, and AMSTAR 2 grades and used the Jadad decision algorithm to generate recommendations. 20 meta-analyses fulfilling the eligibility criteria were included. The AMSTAR scores of the included studies varied from 6–10 (mean:7.9). All the included studies had critically low reliability in their summary of results due to their methodological flaws according to AMSTAR 2 grades. The initial size of the tear and type of repair performed do not seem to affect the benefit of PRPs. Among the different preparations used, leucocyte poor (LP)-PRP possibly offers the greatest benefit as a biological augment in these situations. Based on this systematic overview, we give a Level II recommendation that intra-operative use of PRPs at the bone-tendon interface can augment the healing rate, reduce re-tears, enhance the functional outcomes and mitigate pain in patients undergoing arthroscopic rotator cuff repair

Introduction. Rotator cuff healing after an arthroscopic repair is discussible because of the high incidence of failures. Among biologic augmentations currently used, platelet-rich plasma (PRP) is one of the most applied, supposed to enhance and accelerate the healing process in different musculoskeletal disorders. However, the evidence supporting its successful administration is still lacking, especially in the field of the rotator cuff repair. Our purpose is to clarify if the recovery is accelerated and the integrity of repaired construct is increased in patients undergoing PRP injections after arthroscopic repair of the rotator cuff. Patients & Methods. Thirty-eight patients with full-thickness rotator cuff tears have been enrolled after they had been informed about the use of PRP and the timing of its application postoperatively. Seventeen patients underwent arthroscopic rotator cuff repair and PRP injections (3 injections at 10 days each other), 21 underwent arthroscopic rotator cuff repair without PRP injections. Outcomes were assessed preoperatively, at 3, 6, 12, and minimum 16 months after surgery (average 17.7 +/− 1.7 months). Constant system, the University of California at Los Angeles (UCLA) system and a Visual Analogue Scale (VAS) scale were used; range of motion and strength in all planes were also assessed. The healing of the repair was assessed at magnetic resonance imaging at a minimum follow up of 6 months from surgery. All patients had the same rehabilitation protocol. Results. Platelet-rich plasma gel application after to arthroscopic rotator cuff tear repairs did not accelerate recovery with respect to pain, range of motion, strength, functional scores, or overall satisfaction as compared with conventional repair at any time point. There was no difference between the 2 groups after 3, 6, 12, months and at final follow up. The follow-up MRI showed no significant difference in the healing rate of the rotator cuff tear. In addition, magnetic resonance imaging, at a minimum of 6 months after surgery, demonstrated a retear rate of 23.5 % in the PRP group and 19% in the conventional group, there was no statistical significance between the groups (P = .658). Discussion/Conclusion. Although PRP application after arthroscopic repair of the rotator cuff has no effects on clinical recovery and structural integrity, it reduces the postoperative occurrence of shoulder stiffness. Further studies should support these findings

Surgical reattachment of torn rotator cuff tendons can lead to satisfactory clinical outcome but failures remain common. Ortho-R product is a freeze-dried formulation of chitosan (CS) that is solubilized in platelet-rich plasma (PRP) to form injectable implants. The purpose of the current pilot study was to determine Ortho-R implant acute residency, test safety of different implant doses, and assess efficacy over standard of care in a sheep model. The infraspinatus tendon (ISP) was detached and immediately repaired in 22 skeletally mature ewes. Repair was done with four suture anchors in a suture bridge configuration (n = 6 controls). Freeze-dried formulations containing 1% w/v chitosan (number average molar mass 35 kDa and degree of deacetylation 83%) with 1% w/v trehalose (as lyoprotectant) and 42.2 mM calcium chloride (as clot activator) were solubilized with autologous leukocyte-rich PRP and injected at the tendon-bone interface and on top of the repaired site (n = 6 with a 1 mL dose and n = 6 with a 2 mL dose). Acute implant residency was assessed histologically at 1 day (n = 2 with a 1 mL dose and n = 2 with a 2 mL dose). Outcome measures included MRI assessment at baseline, 6 weeks and 12 weeks, histopathology at 12 weeks and clinical pathology. MRI images and histological slides were scored by 2 blinded readers (veterinarian and human radiologist, and veterinarian pathologist) and averaged. The Generalized Linear Model task (SAS Enterprise Guide 7.1 and SAS 9.4) was used to compare the different groups with post-hoc analysis to test for pairwise differences. Ortho-R implants were detected near the enthesis, near the top of the anchors holes and at the surface of ISP tendon and muscle at 1 day. Numerous polymorphonuclear cells were recruited to the implant in the case of ISP tendon and muscle. On MRI, all repair sites were hyperintense compared to normal tendon at 6 weeks and only 1 out 18 repair sites was isointense at 12 weeks. The tendon repair site gap seen on MRI, which is the length of the hyperintense region between the greater tuberosity and tendon with normal signal intensity, was decreased by treatment with the 2 mL dose when compared to control at 12 weeks (p = 0.01). Histologically, none of the repair sites were structurally normal. A trend of improved structural organization of the tendon (p = 0.06) and improved structural appearance of the enthesis (p = 0.1) with 2 mL dose treatment compared to control was seen at 12 weeks. There was no treatment-specific effect on all standard safety outcome measures, which suggests high safety. Ortho-R implants (2 mL dose) modulated the rotator cuff healing processes in this large animal model. The promising MRI and histological findings may translate into improved mechanical performance, which will be assessed in a future study with a larger number of animals. This study provides preliminary evidence on the safety and efficacy of Ortho-R implants in a large animal model that could potentially be translated to a clinical setting

Although mechanical stabilisation has been a hallmark of orthopaedic surgical management, orthobiologics are now playing an increasing role. Platelet-rich plasma (PRP) is a volume of plasma fraction of autologous blood having platelet concentrations above baseline. The platelet α granules are rich in growth factors that play an essential role in tissue healing, such as transforming growth factor-β, vascular endothelial growth factor, and platelet-derived growth factor. PRP is used in various surgical fields to enhance bone and soft-tissue healing by placing supraphysiological concentrations of autologous platelets at the site of tissue damage. The easily obtainable PRP and its possible beneficial outcome hold promise for new regenerative treatment approaches. The aim of this literature review was to describe the bioactivities of PRP, to elucidate the different techniques for PRP preparation, to review animal and human studies, to evaluate the evidence regarding the use of PRP in trauma and orthopaedic surgery, to clarify risks, and to provide guidance for future research

OBJECTIVE: The purpose of this study is to examine the effect of a single percutaneous injection of platelet-rich-plasma compared to an injection of corticosteroids in patients with chronic lateral epicondylitis. BACKGROUND: Lateral epicondylitis is a common problem that usually resolves with nonoperative treatments. Platelet Rich Plasma (PRP) is a component of whole blood that contains concentrated amounts of powerful growth factors. PRP has been used for a variety of orthopedic applications including tendinopathy, wound healing and spinal fusion with varying degrees of success. Buffered PRP has also been used to enhance cell proliferation in-vitro. HYPOTHESIS: Treatment of chronic severe lateral epicondylitis with buffered platelet-rich plasma will reduce pain and increase function in patients considering surgery for their problem. METHODS: One hundred patients with persistent lateral epicondylar pain were evaluated in this study. All these patients were initially given a variety of nonoperative treatments. These patients had significant persistent pain for at least 3 months despite these interventions. All patients were considering surgery. This cohort of patients who had failed nonoperative treatment was then given either a single percutaneous injection of platelet-rich plasma (experimental group, n = 50) or corticosteroids (control group, n = 50). RESULTS: PRP has a significant better effect on lateral epicondylitis than corticosteroid injections. CONCLUSION: This in-vivo data suggest that tendon healing is occurring in lateral epicondylitis using PRP

Introduction. The use of stem cell and platelet-rich plasma (PRP) injections for knee osteoarthritis (OA) is extremely controversial and at best experimental. These treatments are being given to patients across the nation for “cash only payments”. Our objectives were (1) to determine the proportion of board certified orthopedic surgeons who offer stem cell or PRP treatment for knee OA, (2) how much the practices charge for those treatments and (3) if members of the knee society use these therapies. Methods. Board certified orthopedic surgeons’ offices in our county were identified by their AAOS active membership. Knee society membership roll was also utilized. Offices were contacted by telephone and presented with a hypothetical patient with end stage knee osteoarthritis searching for specific treatment (stem cells or PRP injections). T-test was used to compare the Dade county board certified orthopedists to knee society members. Results. A total of 186 board certified orthopedic surgeons’ offices were contacted. 17.6% of all contacted orthopedics offices offered PRP and 12.5% offered stem cell treatments. 61.2% of the offices were transparent on the pricing of PRP while 31.8% gave a price for stem cell therapy. The remaining practices stated that pricing would be “determined or discussed” during a scheduled visit. Mean cost for a PRP injection was $887 (SE 101; range: $350–$1700) and for a stem cell injection was $2800 (SE 852; range: $1000–$6000). Usage of these therapies amongst general AAOS members and Knee Society members was found to be significantly different for both PRP and stem cells (17% vs. 10%; p<0.001 and 26% vs. 13%; p<0.001, respectively). No practice had a “free” research protocol to study the treatments. Conclusions. Biological injectables as a treatment for knee OA has theoretical potential promise in the management of arthritis but continues to be at best investigational. Knee Society members demonstrated significantly more caution using these treatments

Intra-articular injections of human mesenchymal stromal cells (MSCs) and platelet-rich plasma (PRP) have been intensively investigated as therapies for knee osteoarthritis (OA) with positive outcomes. In this work we evaluated weather a combination of the treatments (MSCs + PRP) would be beneficial compared to MSCs alone (MSCs) and standard corticosteroid injection (Control group). Forty seven patients (24 males and 23 females; 53.3 ± 10.7 years old) with radiographic symptomatic knee OA (Dejour grades II–IV) were randomized to receive intra-articular injections of MSCs (n = 16), MSCs + PRP (n = 14) or corticosteroid (n=17). MSCs were obtained after mononuclear cells separation from bone marrow aspiration collected from both posterior iliac crests using Sepax automated closed system and expanded in culture until reaching the number of 4 × 10. 7. PRP was obtained by double-centrifugation of whole blood according to a protocol developed in house. After 12 months follow-up, the MSCs and MSCs+PRP groups achieved higher percentages of expected improvement when comparing to the corticosteroid group for the KOOS-symptoms, pain, function and daily living, domains and global score. For the population older or equal to 60 years old the MSCs+PRP group showed significant superiority for the KOOS-ADL domain at 12 months. Cytokines quantification evidenced anti-inflammatory aspects of the treatments. This work evidences the safety and efficacy of intra-articular injection of MSCs for the treatment of early knee OA, with greater improvement with PRP addition particularly to the older population

The objective of this study was to evaluate the safety and the effect of platelet-rich plasma (PRP) intra-articular injections obtained from blood donors (homologous PRP) on elderly patients with early or moderate knee osteoarthritis (OA) who are not candidates for autologous PRP treatment. A total of 60 symptomatic patients, aged 65–86 years, affected by hematologic disorders and early or moderate knee OA, were treated with 5 ml of homologous PRP intraarticular injections every 14 days for a total of three injections. Clinical evaluations before the treatment, and after 2 and 6 months were performed by International Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome Score (KOOS) and Equal Visual Analogue Scale (EQ VAS) scores. Adverse events and patient satisfaction were recorded. No severe complications were noted during the treatment and the follow-up period. A statistically significant improvement from basal evaluation to the 2-month follow-up visit was observed, whereas a statistically significant worsening from the 2-month to the 6-month follow-up visit was showed. The overall worst results were observed in patients aged 80 years or over and in those affected by minor bone attrition. It was found that 90% of patients were satisfied at the 6-month evaluation. Homologous PRP has an excellent safety profile but offers only a short-term clinical improvement in selected elderly patients with knee OA who are not candidates for autologous PRP treatment. Increasing age and developing degeneration result in a decreased potential for homologous PRP injection therapy. Further studies are needed to confirm these findings

Greater trochanteric pain syndrome is a painful condition characterised by pain around the greater trochanter usually affecting middle-aged women. The majority of patients will improve with conservative management such as physiotherapy and non-steroidal anti-inflammatory drugs (NSAIDs); however, if this fails then more invasive treatments including corticosteroids and surgery may be required. Platelet-rich plasma (PRP) is an autologous blood product, which has a higher concentration of growth factors postulated to provide enhanced healing and anti-inflammatory properties. The Hip Injections PRP Vs Placebo (HIPPO) trial aims to assess the ability of ultrasound-guided PRP injections to improve symptoms and function in patients with GTPS. 64 patients were enrolled and randomised to either the PRP or placebo (normal saline) treatment arm. Two patients decided to drop out of the trial. Clinical outcomes in both groups were evaluated and compared using the International Hip Outcome Tool-12 (iHOT12), Visual Analogue Scale (VAS) of pain, the modified Harris Hip Score (mHHS) and the presence or absence of complications at 3 and six months. The level of significance was set at p<0.05. Both groups received physiotherapy after the injections. The mean age was 57.5. There were 6 males and 56 females with M:F ratio of 1:9.3. Both groups were similar in terms of demography and preoperative scores. The iHOT12 score improved from 28.23 to 45.42 at three-months and decreased slightly to 42.44 at six-months in the Placebo group. The iHOT12 in the PRP group improved from 35.51 to 44.47 at three-months and decreased to 39.78 at six-months. Both groups showed improved VAS and mHHS at three-months compared to the baseline with no statistically significant difference between the two groups (p >0.05). The scores decreased at six-months however remained above the baseline. No complications were reported. Gender and age had no effect on outcomes. Both groups similarly improved from baseline. Physiotherapy can be considered as an important factor in patients' treatment. Further research should be conducted to investigate the role of physiotherapy in the treatment of GTPS

The use of platelet-rich plasma (PRP) as an adjuvant to tissue repair is gaining favour in orthopaedic surgery. Tunnel widening after anterior cruciate ligament (ACL) reconstruction is a recognised phenomenon that could compromise revision surgery. The purpose of this study was to determine whether PRP might prevent tunnel widening in ACL reconstruction. Patients undergoing ACL reconstruction using a hamstring graft were randomly allocated either to have PRP introduced into the tunnels peri-operatively or not. CT scanning of the knees was carried out on the day after surgery and at three months post-operatively and the width of the tunnels was measured. Patients were also evaluated clinically at three months, when laxity was also measured. Each group comprised 25 patients, and at three months post-operatively all were pain-free with stable knees, a negative Lachman test and a good range of movement. Arthrometric results had improved significantly in both groups (p < 0.001). Despite slightly less tunnel widening in the PRP group, there was no significant difference between the groups at the femoral opening or the mid-tunnel (p = 0.370 and p = 0.363, respectively) nor at the tibial opening or mid-tunnel (p = 0.333 and p = 0.177, respectively). We conclude that PRP has no significant effect in preventing tunnel widening after ACL reconstruction. Cite this article: Bone Joint J 2013;95-B:65–9

Introduction. Interest in platelet-derived growth factors has been increasing as an adjunct in surgical techniques for tissue repair. Its use in ligament injuries repair has been studied mainly in animals. The authors intend to study growth factors influence in ACL repair using BTB graft. Material. 20 individuals underwent ACL rupture BTB arthroscopic repair, using Double Incision Mini-Invasive Technique. MRI (3-Tesla) images. GPSIII ® System to obtain Platelet-Rich Plasma (PRP) thrombin activated. Methods. Prospective study consisting of 2 groups of 10 patients each. Surgical technique, fixation method and postoperative protocol were the same. In the study group (SG-10 patients) graft was imbued with PRP and the remaing plasma was intra-articularly injected. The MRIs took place 6 weeks and 6 months after the procedure with and without gadolinium-DTPA enhancement. Evaluation was performed blindly by independent radiologists concerning femoral tunnel integration, sinovialization process and nonspecific synovitis. Clinical and functional status evaluation: IKDC. Statistical analysis in SPSS®. Results. Radiological evaluation was similar in both groups. In the Study Group at 6 weeks we verified less joint effusion and synovitis. At 6 months: no diference in integration in femoral tunnel, and in granulation tissue around the femoral tunnel in graft sinovialization. IKDC (mean ± SD) with PRP: pre-operative −45,66 ±6,98, post-operative −94,35 ±3,54 (Age-29 ± 10), without PRP: preoperative −48,02 ±12,68, post-operative −91,7 ±6,99 (Age −31 ±10). There are no statistical differences between the groups with and without PRP in clinical and functional assessments and MRI images. Discussion. The use of technology to accelerate and improve the processes of tissue repair and integration is of great interest in repairing the ACL. Studies in humans are rare, with low level of evidence and contradictory results. Although the limitations of this study, it seems to us that the use of growth factors has no advantages in the process of PT graft integration at 6 months. Conclusion. PRP doesn't seem to contribute to enhancement of the ligamentation process and articular rehabilitation when used as a step of BTB technique

Osteoarthritis (OA) is a debilitating disease characterised by degradation of articular cartilage and subchondral bone remodeling. Current therapies for early or midstage disease do not regenerate articular cartilage, or fail to integrate the repair tissue with host tissue, and therefore there is great interest in developing biological approaches to cartilage repair. We have shown previously that platelet-rich plasma (PRP) can enhance cartilage tissue formation. PRP is obtained from a patient's own blood, and is an autologous source of many growth factors and other molecules which may aid in healing. This raised the question as to whether PRP could enhance cartilage integration. We hypothesise that PRP will enhance integration of bioengineered cartilage with native cartilage. Chondrocytes were isolated from bovine metacarpal-phalangeal joints, seeded on a porous bone substitute (calcium polyphosphate) and grown in the presence of FBS to form an in vitro model of osteochondral-like tissue. After 7 days, the biphasic constructs were soaked in PRP for 30 minutes prior to implantation into the core of a ring-shaped biphasic explant of native bovine cartilage and bone. Controls were not soaked in PRP. The resulting implant-explant construct was cultured in a stirring bioreactor in serum free conditions for 2 weeks. The integration zone was visualised histologically. A push-out test was performed to assess the strength of integration. Matrix accumulation at the zone of integration was assessed biochemically and the gene expression of the cells in this region was assessed by RT-PCR. Significance (p<0.05) was assessed by a student's t-test or one-way ANOVA with tukey's post hoc. PRP soaked bioengineered implants, integrated with the host tissue in 73% of samples, whereas control bioengineered implants only integrated in 19% of samples based on macroscopic evaluation (p<0.05). The integration strength, as determined by the normalised maximum force to failure, was significantly increased in the PRP soaked implant group compared to controls (219 +/− 35.4 kPa and 72.0 +/− 28.5 kPa, respectively, p<0.05). This correlated with an increase in glycosaminoglycan and collagen accumulation in the region of integration in the PRP treated implant group, compared to untreated controls after 2 weeks (p<0.05). Immunohistochemical studies revealed that the integration zone was rich in collagen type II and aggrecan. The cells at the zone of integration in the PRP soaked group had a 2.5 fold increase in aggrecan gene expression (p=0.05) and a 3.5 fold increase in matrix metalloproteinase 13 expression (p<0.05) compared to controls. PRP soaked bio-engineered cartilage implants showed improved integration with native cartilage compared to non-treated implants, perhaps due to the increased matrix accumulation and remodeling at the interface. Further evaluation is required to determine if PRP improves integration in vivo

Platelet Rich Plasma (PRP), either rich (L-PRP) or poor (P-PRP) of leukocytes, is frequently used as an anti-inflammatory and regenerative tool in osteoarthritis (OA). PRP contains proteins but not genes as it is derived from megakaryocytes. Proteomics but not metabolomics of PRP was recently studied. Metabolomics is a field of ‘omics’ research involved in comprehensive portrayal of the small molecules, metabolites, in the metabolome. These small molecules can be endogenous metabolites or exogenous compounds found in an organism (1). Our aim was to determine the difference between L-PRP and P-PRP.

A cross-sectional clinical study was designed in six recreational male athletes between the ages of 18 and 35 years. 3 mL P-PRP and 3 mL -LPRP was prepared from 60 mL of venous blood after treating with 9 mL of sodium citrate and centrifugation at 2.700 rpm for 10 min. Half of the prepared PRP's were frozen at −20°C for a week. Fresh and frozen samples were analyzed at the Q-TOF LC/MS device after thawing to room temperature.

Untargeted metabolomic results revealed that the metabolomic profile of the L-PRP and P-PRP were significantly different from each other. A total of 33.438 peaks were found. Statistically significant (p<0.05) peaks were uploaded to the MetaboAnalyst 5.0 platform. Exogenous out of 2.308 metabolites were eliminated and metabolites found significant for our study were subjected to pathway analysis. Steroid biosynthesis, sphingolipid metabolism and metabolism of lipid pathways were affected. In the L-PRP samples, Nicotinamide riboside (FC: 2.2), MHPG (FC: 3.0), estrone sulfate (FC: 7.5), thiamine diphosphate (FC: 2.0), leukotriene E4 (FC: 7.5), PC(18:1 (9Z)e/2:0) (FC: 9.8) and Ap4A (FC: 2.1) were higher compared to P-PRP. C24 sulfatide (FC: −11.8), 3-hexaprenyl-4,5-dihydroxybenzoic acid (FC: −2.8) metabolites were furthermore lower in P-PRP. Clinical outcomes of PRP application should consider these metabolic pathways in future studies (2).

Background:. Blood loss, pain and wound healing contribute significantly to the perioperative morbidity after total knee arthroplasty. Prospective randomized controlled studies are lacking, to our knowledge. The purpose of this study was to determine whether platelet rich plasma (PRP) might prevent blood loss and postoperative pain and expedite wound healing following TKA. Methods:. Forty consecutive age, sex and BMI-matched patients who had unilateral or bilateral arthritis of the knee with similar deformity and preoperative range of motion were enrolled for this prospective randomized controlled double blinded clinical trial. Preoperative haemoglobin, range of motion, WOMAC and KSS scores were noted. Platelet-rich plasma was applied over the wound including the capsule, medial and lateral recesses in seventeen patients. Twentythree served as controls. Postoperative haemoglobin, blood loss, blood transfusion, VAS score, Wound score, KSS and WOMAC score were recorded and evaluated. Results:. Autologous platelet gel (APG) group had a smaller decrease in haemoglobin (Preop Hb–POD3 Hb) compared to control (1.97/3.56; p = 0.00). Postoperative blood loss was 173.2 ml vs 220.4 ml (p = 0.02). Blood transfusion was significantly less in the APG group (0.59 units/1.43 units; p = 0.001). APG group experienced less pain immediately, at 6 weeks and 12 weeks postoperatively (VAS 6.5/7.39, 2.67/3.84, 1.61/2.31; p = 0.00, 0.00, 0.00) and required fewer narcotics than control (15.24/22.65; p = 0.00). There was statistically significant difference in ROM at 5. th. day, 6 weeks and 3 months (79.44°/74.22°, 96.11°/87°, 97.6°/93.9° respectively; p = 0.00, 0.00, 0.01). There was no significant difference in the wound scores of two groups (30.96/34.23; p = 0.311). Significant difference was observed in KSS and WOMAC scores at 6 weeks (158.96/148.77, 17.3/23; p = 0.00, 0.00) and 12 weeks (166.96/161.42, 10.86/14.61; p = 0.00, 0.00). However no significant difference was found at 6 months. Conclusions:. We found significant reduction in blood loss, postoperative pain and need for narcotics after the use of autologous platelet gel in patients of total knee arthroplasty. Quicker and better functional outcome was observed in the APG group. However, at six months and later follow up, both groups had similar functional scores. Its role on wound healing was statistically insignificant. Level of Evidence: Therapeutic Level II

Background

Disability and slow return to sport and work after tendon rupture are major challenges. Platelet Rich Plasma (PRP) is an autologous supraphysiological concentration of platelets from whole blood that has demonstrated positive cellular and physiological effects on healing in laboratory conditions but evidence from adequately powered robust clinical trials is lacking. We aimed to determine the clinical efficacy of PRP for treatment of acute Achilles tendon rupture.

Background

The PATH-2 trial found no evidence of a benefit of Platelet Rich Plasma (PRP) injection versus a placebo after Achilles tendon rupture (ATR) at six-months. ATR often leave longer-term functional deficiencies beyond six-months. This study aim is to determine if PRP affect tendon functional outcomes at two-years after rupture.

Background. A cell-based tissue-engineered construct can be employed for treating meniscal lesions occurring in the non-vascularized inner two-thirds. The objective of this study was to test the hypothesis that both pre-differentiation of human bone marrow derived stromal cells (hBMSCs) into chondrogenic lineage before cell seeding and platelet-rich plasma (PRP) pretreatment on a PLGA mesh scaffold enhances the healing capacity of the meniscus with hBMSCs-seeded scaffolds in vivo. Methods. PRP of 5 donors was mixed and used for the experiments. The woven PLGA mesh scaffold (VicrylTM, Ethicon) measuring 20×8 mm (thickness, 0.2 mm) was prepared. The scaffolds were immersed into 1,000 μl of PRP and were centrifuged at 150g for 10 min. Then, the scaffold was flipped 180° and the same procedure was done for the other side. After washing, the scaffolds were soaked into 1,000 μl of DMEM media. hBMSCs from an iliac crest of 10 patients after informed consent and approval of our IRB were induced into chondrogenic differentiation with chondrogenic media containing 10 ng/ml rhTGF-ß3 in 1.2% alginate bead culture system for 7 days. Then, 2×10. 5. hBMSCs were recovered, seeded onto the scaffold, and cultured under dynamic condition. Based on the presence of pre-differentiation into chondrogenic lineage and the PRP pretreatment, 4 study groups were prepared. (no differentiation without PRP, no differentiation with PRP, chondrogenic differentiation without PRP, chondrogenic differentiation with PRP) Cell number for each cell-seeded scaffold was determined at 24 hours after seeding. Then, scaffolds were placed between human meniscal discs and were implanted subcutaneously in nude mice for 6 weeks (n=10 per group). Results. Cell attachment analysis revealed no significant difference among groups (p>0.05). The average cell number attached on the scaffold was ranged 1.1×10. 5. to 1.2×10. 5. among groups after 24 hours, so the initial cell seeding efficiency was ranged 55 to 60%. Histologic results from the 10 constructs containing hBMSCs undifferentiated and seeded onto non-PRP treated scaffolds revealed none had healed at all. Of the constructs containing hBMSCs undifferentiated and seeded onto PRP-pretreated scaffolds, three menisci healed and seven did not heal. Of the constructs containing hBMSCs pre-differentiated into chondrogenic lineage and seeded onto non-PRP treated scaffolds, six menisci healed and four did not heal. Of the constructs containing hBMSCs pre-differentiated into chondrogenic lineage and seeded onto PRP-pretreated scaffolds, seven menisci healed and three did not heal. Histological evaluation demonstrated a continuous hypercellular new fibrous tissue integrating into the native devitalized meniscus disc tissue in healed samples. The histological outcome between the groups was significant (p<0.05) (Table 1) (Figure 1). Conclusion. hBMSCs, which were differentiated into chondrogenic lineage before cell seeding and attached PRP-pretreated PLGA mesh scaffolds, demonstrated enhanced healing capacity of human meniscus in a meniscal repair mouse model. These findings demonstrate that both pre-differentiation of hBMSCs into chondogenesis and the PLGA scaffold modified by PRP pretreatment provides more biomimetic and biocompatible strategy for cell-mediated meniscal repair. Acknowledgements. This study was supported by Basic Science Research Program through the National Research Foundation of Korea (#2015-01004099)

Introduction. Osteochondral defects (OCDs) of the talus are treated initially by arthroscopic bone marrow stimulation. For both large and secondary defects, current alternative treatment methods have disadvantages such as donor site morbidity or two-stage surgery. Demineralized bone matrix (DBM) was published for the treatment of OCDs of rabbit knees. Autologous platelet-rich plasma (PRP) may improve the treatment effect of DBM. We previously developed a goat model to investigate new treatment methods for OCDs of the talus. The aim of the current study was to test whether DBM leads to more bone regeneration than control OCDs, and whether PRP improves the effectiveness of DBM. Methods. A standardized 6-mm OCD was created in 32 ankles of 16 adult Dutch milk goats. According to a randomized schedule, 8 goats were treated with commercially available DBM (Bonus DBM, Biomet BV, Dordrecht, the Netherlands) hydrated with normal saline, and 8 were treated with the same DBM but hydrated with autologous PRP (DBM+PRP). The contralateral ankles (left or right) were left untreated and served as a control. The goats were sacrificed after 24 weeks and the tali were excised. The articular talar surfaces were assessed macroscopically using the international cartilage repair society (ICRS) cartilage repair assessment, with a maximum score of 12. Histologic analysis was performed using 5-μm sections, and histomorphometric parameters (bone% and osteoid%) were quantified on representative areas of the surface, center, and peripheral areas of the OCDs. Furthermore, μCT-scans of the excised tali were obtained, quantifying the bone volume fraction, trabecular number, trabecular thickness, and trabecular spacing in both the complete OCDs and the central 3-mm cylinders. Results. All goats recovered well and were able to bear full weight within 24 hours after surgery. The mean ICRS-score of the ankles treated with DBM was 8.0 ± 1.0, compared to a score of 8.4 ± 1.5 in the contralateral ankle (NS); those treated with DBM+PRP scored 6.9 ± 2.4, compared to 7.4 ± 2.0 in the contralateral ankle (NS). Histologic analysis showed four different patterns of healing, distributed evenly over the treatment and control groups: type 1 (n = 4), almost completely healed; type 2 (n = 11), restoration of the subchondral bone with a cystic lesion underneath; type 3 (n = 14), superficial defect with regeneration from the margins and bottom; type 4 (n = 3), no healing tendency. Histomorphometry and μCT revealed no statistically significant difference between treatment (DBM or DBM+PRP) and contralateral control or between both treatment groups in any of the parameters investigated. Conclusion. No treatment effect of DBM was found compared to control defects, and the addition of PRP was not beneficial

Aim: This study wants to investigate whether the administration of stromal stem cells (SSC) in a platelet-rich plasma (PRP) scaffold could promote angiogenesis which resulted in a better allograft integration. Methods: surgery: A monolateral resection of 3cm segment of the metatarsus, was perfomed in 10 adult cross-breed sheep (3–4 years old), weighting 60–70 kg. Isolation and ex-vivo expansion of SSC: nucleated cells were isolated with density gradient and expanded ex-vivo with alpha-MEM containing 20% FCS. Radiographic and histomorphometric analysis: Radiographs were made after surgery and after 1, 2 and 4 months. Histomorphometric studies were carried out to study the defect and the new bone formation at the implant site. Results: Union had occurred in all the 5 animals of the SSC group after 4 months as observed radiographically and morphologically, while in the control group the osteotomy line was still visible. Histomorphometric analysis demonstrated a higher % of new-bone formation in both the host (%section quadrant) and the grafted bone in SSC animals. Conclusions: Results presented suggest that SSC in PRP-based scaffold have improved allograft integration. In conclusion the application of this surgical approach may result in an increased and accelerated bone graft integration, reducing the time required for bone healing and increasing the chances of a successful bone implant

Abstract

The reconstruction of large bone segments is a major goal in orthopaedic surgery. Autologous cancellous bone is recognized as the most biologically active graft material, but autologous bone harvest is associated with significant morbidity and founds its limit in the available quantity. Biomaterials or allografts do not encounter these limitations, but have no osteogenic and limited osteinductive potential. In order to enhance tissue regeneration and healing we have tried to obtain a graft with osteconductive, inductive and osteogenic properties. The day before operation 350 cc of autologous blood is donated from the patient and centrifuged to obtain a platelet-rich plasma. Bone marrow is aspirated from the posterior iliac crests with the patient under spinal anaesthesia and is processed to increase its stem cell content. The structural scaffold used is morcellized cancellous bone provided from our Bone Bank. At operation bone is mixed with bone marrow buffy coat and Platelet Rich Plasma in a sterile glass becker with addition of CaCl2 till clot formation to produce a gel-like component that is handled easily. We have utilized this technique from November 2000 till January 2004 for 68 patients: 41 of these patients required healing of large bone defects: 22 males and 19 females. Fresh bone marrow alone was used for a percutaneous injection in 11 cases; open surgery with autologous growth factors, bone marrow buffy coat and allograft was used in 30 patients. The radiological and clinical results showed early healing of the defects treated with this technique and no complications related to the procedure at an average follow up of 23 months (3–40)

Introduction

Collapse of femoral head associated with end-stage arthritis form hallmark of osteonecrosis of femoral head. Purpose was to assess efficacy of platelet rich plasma following core decompression in early stage of osteonecrosis of femoral head.

Rotator cuff disease encompasses a spectrum from partial to full thickness tears. Despite being 2–3 times more common than full–thickness tears, effective non-operative treatment for partial thickness tears has remained elusive. Platelet enriched plasma (PRP) has been proposed to enhance rotator cuff healing by enhancing the natural healing cascade. However, its utility in rotator cuff disease remains controversial. The purpose of this study was to compare the patient reported outcomes between PRP and corticosteroid injection in patients with symptomatic partial thickness tears.

This double blind randomized controlled trial enrolled patients with symptomatic, partial thickness rotator cuff tears or rotator cuff tendinopathy proven on ultrasound or MRI. Patients were randomized to either corticosteroid or PRP ultrasound-guided injection of the affected shoulder. Patients completed patient reported outcomes at 6 weeks and 12 weeks. The primary outcome was Visual Analog Scale (VAS) pain scores. Secondary outcomes included the Western Ontario Rotator Cuff (WORC) index, American Shoulder and Elbow Surgeons (ASES) score, and failure of non-operative management as determined by consent for surgery or progression to operative intervention.

Ninety-nine patients were enrolled in the study with equal demographics between the two groups. Taking into account pre-injection scores, patients with PRP injections demonstrated a statistically significant improvement in VAS scores compared to patients receiving corticosteroid injections at 12 weeks (p=0.045) but not at 6 weeks (p=0.704). There was no difference in other outcome measures or progression of the two groups to surgical intervention.

The use of PRP in the management of partial thickness rotator cuff tears demonstrates significant improvement of pain scores at 12 week follow up compared to corticosteroid injections. However, this did not affect the rate of progression to surgical intervention. Continued study is required to determine the utility of PRP in this patient population.

Introduction and Objective

Platelet-Rich-plasma (PRP) has been used in combination with stem cells, from different sources, with encouraging results both in vitro and in vivo in osteochondral defects management. Adipose-derived Stem Cells (ADSCs) represents an ideal resource for their ease of isolation, abundance, proliferation and differentiation properties into different cell lineages. Furthermore, Stem Cells in the adipose tissue are more numerous than from other sources. Aim of this study was to evaluate the potential of ADSCs in enhancing the effect of arthroscopic mesenchymal stimulation combined with infiltration of PRP.

Introduction

Lateral epicondylitis, also known as “tennis elbow,” is a degenerative disorder of the common extensor origin of the lateral humeral epicondyle. The mainstay of treatment is non-operative and includes physiotherapy, activity modification, bracing, nonsteroidal anti-inflammatory drugs, and injections. There is a subgroup of patients however who do not respond to non-operative measures and require operative intervention.

Injured skeletal muscle repairs spontaneously via regeneration, however, this process is often incomplete because of fibrotic tissue formation. In our study we wanted to show improved efficiency of regeneration process induced by antifibrotic agent decorin in a combination with Platelet Rich Plasma (PRP)-derived growth factors. A novel human myoblast cell (hMC) culture, defined as CD56 (NCAM)+ developed in our laboratory, was used for evaluation of potential bioactivity of PRP and decorin. To determine the their effect on the viability of hMC we performed a MTT assay. To perform the cell proliferation assay, hMCs were separately seeded on plates at a concentration of 30 viable cells per well. Cell growth medium prepared with different concentrations of PRP exudates (5%, 10%, and 20%) and decorin (10 ng/mL, 25 ng/mL, and 50 ng/mL) were added and incubated for 7 days. After incubation we stained the cells with crystal-violet and measured the absorbance.

To study the expression of Transforming Growth Factor Beta (TGF-β) and myostatin (MSTN), two main fibrotic factors in the process of muscle regeneration we performed several ELISA assays in groups treated with all therapeutic agents (PRP, decorin and their combination). Further, we have studied the ability of these agents to influence the differential cascade of dormant myoblasts towards fully differentiated myotubes by monitoring step wise activation of single nuclear factors like MyoD and Myogenin via multicolor flow cytometry. We stained the cells simultaneously with antibodies against CD56, MyoD and myogenin. We acquired cell images of 5,000 events per sample at 40 x magnification using 488 nm and 658 nm lasers and fluorescence was collected using three spectral detection channels. We analysed the cells populations according to expression of single or multiple markers and their ratios.

Finally, we examined the treated cell populations using a multicolour laser microscope after staining for desmin (a key marker of myogenic differentiation of hMC), α-tubulin, and nuclei. Optical images were acquired at the center of chamber slides where the cell density is at its highest using a Leica TCS SP5 II confocal microscope and analysed using Photoshop CS6, where a “Color Range” tool was used in combination with a histogram palette to count the pixels that correspond to desmin-positive areas in an image.

The mitochondrial activity of cells, as determined by the MTT assay, was significantly increased (p < 0 .001) after exposure to tested concentrations of PRP exudate. Similarly, viability was elevated in all tested concentrations of decorin. PRP exudate enhanced the viability of cells to more than 400% when compared to the control (p < 0 .001). The viability of cells treated with PRP exudates was also significantly higher when compared to decorin (p < 0 .001). Decorin did not show a significant effect on cell proliferation compared to the control, however, cultivation with PRP exudate leads to a 5-fold increase in cell proliferation (p < 0 .001). Decorin was shown to down-regulate the expression of TGF-β when compared to the control by more than 15% (p < 0 .001) but significantly less than PRP exudate p < 0 .005). PRP significantly down-regulated TGF-β expression by more than 30% (p < 0 .001). Similarly, the MSTN expression levels were significantly down-regulated by decorin and PRP. MSTN levels of cells treated with decorin were decreased by 28.4% (p < 0 .001) and 23.1% by PRP (p < 0 .001) when compared to the control group.

Using flow cytometry we detected a 39.1% increase in count of myogenin positive cells in the PRP-treated group compared to the control. Moreover, there was a 3.09% increase in cells positive only for myogenin, whereas no such cells were found in the control cell population. The population of cells positive only for myogenin is considered as fully differentiated and capable of fusion into myotubes as well as future mucle fibers and is thus of great importance for muscle regeneration. At the same time 20.6% fewer cells remained quiescent (positive only for CD56). Cells positive for both MyoD and myogenin represent the population that shifted significantly towards mature myocites during myogenesis but are not yet fully committed.

Finally, a statistically significant up-regulation of desmin expression (p < 0 .01 for the PRP treated group, p < 0 .005 for the decorin and PRP + decorin treated groups) was present in all therapeutic groups when compared to the control. While no significant difference was found between the PRP and decorin-treated groups, their combination led to a more than 3-fold increase (p < 0 .005) of desmin expression when compared to single bioactives.

PRP can be a highly potential therapeutic agent for skeletal muscle regeneration and repair, especially if in combination with a TGF-β antagonis decorin. Achieving better healing could likely result in faster return to play and lower reinjury rate.

The aim of this study was to evaluate the trochlear bone and cartilaginous regeneration of rabbits using a composite based on platelet rich plasma (PRP), chitosan and hydroxyapatite. The study was approved by the ethics committee of the Federal University of Campina Grande under number 72/2017. Surgical holes measuring four millimetres in diameter were performed in rabbit trochleae, one surgical hole in each animal remained empty and another one was filled with the composite. Clinical-orthopaedic and radiographic evaluations were carried out for 60 days, after which the animals were euthanized for histomorphometric evaluations. Clinical-evaluations exhibited lameness of two members of the treatment (T) group and one member of control (C) group. The radiographic evaluation of T group exhibited absence of subchondral bone reaction (33%); nonetheless, presence of moderate subchondral bone reaction was more frequently reported in group C with 67%. Microscopic evaluation revealed the presence of tissue neoformation, composed of dense connective tissue. Microscopic findings were similar in both groups, with a difference in the amount of neoformed tissue, which was confirmed after the morphometric analysis, revealing a significant difference in the quantity of newly formed tissue at the bone / cartilage / implant interface in the T group. The results indicate that the composite based on chitosan, hydroxyapatite and PRP enhanced bone and cartilage healing.

Angiogenesis is a key factor in early stages of wound healing and is crucial for tissue regeneration. Gold standard for large bone defect treatment is the transplantation of autologous bone grafts, but is not entirely satisfying (e.g. limited amount). Cell therapies and tissue engineering approaches may overcome these problems by using cells and autologous blood components obtainable by less invasive procedures. Pre-clinical studies previously showed promising results combining endothelial progenitor cells (EPCs) and mesenchymal stem cell (MSCs) in polyurethane scaffolds in presence of PRP (1). A systemic investigation of the chemical and mechanical characteristics of different PRP gels formulations suggested their potential use as sustained autologous growth factor delivery system (2). Here we investigate PRP hydrogels as autologous injectable cell delivery systems for EPCs and MSCs and their efficacy in promoting fast neo-vascularization for bone repair applications.

PRP hydrogel and corresponding platelet lysate (PL) were produced from platelet concentrates as described before (3). MSCs were isolated by Ficoll-Paque centrifugation from human bone marrow (EK_regensburg12-101-0127), and cultured in alpha MEM containing 10% FCS and 5 ng/mL basic-FGF (GIBCO). EPCs (CD133+/CD34+) were isolated from MSC fractions using magnetic-activated cell sorting (MACS®) and further cultured in IMDM (GIBCO) containing 5% FCS and 5% PL. GFP positive HUVECs are from Angio-Proteomie, (Boston, USA). Prior to gel encapsulation, MSC and EPCs were pre-stained using PKH26-red® and PKH67-green® respectively. Cells in different proportions were encapsulated in 3D PRP gels, in FDA approved Fibrin gels and in Matrigel®. The gels were cultured in Ibidi microwells placed in an onstage incubator linked to an EVOS Auto Cell Imaging System. The cellular network formation capacity of HUVEC or EPCs and MSC in different proportions was analyzed for the 3 types of hydrogels using time lapse movies recorded over a period of 14 days. Parallel cultures were performed in a classical cell culture CO₂ incubator and sample gels were taken at different time points for additional immunostaining and gene expression analysis.

Preliminary results indicate high cell viability in all of the three tested gels. PRP hydrogels present a favorable environment for the formation of a 3 dimensional cellular network in cell co-culture. The formation of these networks was apparent as early as 4 days after seeding. Networks increase in complexity and branching over time. The same was observed when cells were embedded in Matrigel®, which is known for its pro-angiogenic properties. Further experiments are currently in process looking at the involvement of MSCs in this process and the effect of PRP 3D co-culture on their differentiation.

PRP was previously shown as a potent growth factor delivery system for tissue engineering. In the present work, the high cell viability together with the 3 dimensional capillary-like networks observed at early time points suggest that PRP can also be used as an autologous cell delivery and pro-angiogenic system for bone tissue repair.

Platelet rich plasma has been advocated for the treatment of plantar fasciitis but there are few good quality clinical trials to support its use. We report a pilot double blind randomised controlled trial of platelet rich plasma versus normal saline.

Posterolateral spinal fusion (PSLSF) in rabbits is a challenging model for bone substitutes because the transverse processes are extremely thin and the space to be filled with bone is greater than critical and meiopragic in terms of vascularity.

Several investigators have shown beneficial effects of PRP in bone and soft-tissue healing processes. However, controversial results have been reported in clinical setting analysing the effectiveness of PRP. Aim of the present study was to test the effectiveness of PRP in experimental model of PLSF in rabbits.

Introduction: Activated platelets release various growth factors, some ot which are recognize to improve nerve regeneration. The present study evaluated the effect of platelet-rich-plasma (PRP) in end to end neurorraphy.

Material and method: A total of 38 Spragle-Dawley rats were used. The PRP was obteined from each rat and applicated to the same rat. The left hind limb were used as experimental, with the right as control. The animals were treated in two grups. In both groups the sciatic nerve was dissected from the sciatic notch to the bifurcation. The nerve was transected an repaired with epineural suture (ethilon 9–0). Group A (n=12): suture without PRP. Group B (n=15) suture with PRP. The rats were anestherized and electromyographic studie was performed after the following, 120,5 days for group A and 125,86 for group B. Prior to sacrifice muscular and nerve tissue harvesting was performed.

The amplitude was expressed as the amplitude at the experimental sde divided by the amplitude at the contralateral, untreated side, multiplied by 100%. Recording was done in gastrocnemius and tibialis anterior muscle.

Results: The stimulation was performed in supramaximal form on both groups: Group A: (without PRP)

The mean of intensity was 1.49 mA and the mean of threshold was 0,56 mA

No stadistical difference on both groups was found.

Histological studies were performed and results are no available at the moment of send this abstract

Conclusions:

No evidence has been found that the use of PRP has a beneficial effect on peripheral nerve regeneration

Lateral Epicondylitis is a common condition caused by angiofibroblastic hyperplasia of the tendinous insertion. Its treatment is varied and includes rest, physiotherapy, corticosteroid injection and surgical release. Of late, the role of Platelet Rich Plasma (PRP) injections have been explored, with positive results.

We prospectively assessed the outcomes of lateral epicondylitis treated with PRP injections and compared the outcomes of ultrasound guided and ‘blind’ injection.

This was a single centre prospective cohort study. Patient were assessed with the Disabilities of the Arm, Shoulder and Hand (DASH) Score. PRP was injected into and around the common extensor origin either with or without ultrasound guidance. The primary outcome measure was DASH score at 3 months.

45 (23F:22M) patients were recruited. The mean age was 50 years (range 35 to 79). The mean duration of follow-up was 106 days. The average pre-injection DASH score for both groups combined was 45.5 (11.7–87.5). The mean DASH score at 3 months follow-up was 27.7. The ultrasound guided injection group had a mean improvement in DASH score from 45.5 to 31.2. The “blind” injection group had a mean improvement in DASH from 44.4 to 27.7. No complications were noted. There was no statistically significant difference in improvement in DASH score between the two groups.

Our study provides further evidence to support of the use of PRP injections in the treatment of epicondylitis of the elbow. Interestingly, however, we found that the use of Ultrasound guidance does not appear to improve patient outcomes.

Chronic plantar fasciitis is a common condition but can be difficult to successfully treat. Platelet rich plasma (PRP), a concentrated bioactive component of autologous blood rich in cytokines and other growth factors, was compared with cortisone injection in the treatment of severe cases of plantar fasciitis resistant to traditional non-operative paradigms. Thirty-six patients (16 males 20 females) were prospectively randomized into two study groups. All patients had pre-treatment MRI and ultrasound studies consistent with plantar fasciitis. The first group was treated with a single ultrasound guided injection of 40 mg Depo-Medrol at the injury site and the second group was treated with a single ultrasound guided injection of un-buffered autologous PRP at the injury site. The cortisone group had an average age of 59 (24–74) and had failed 4 months (3–24) of standard non-operative management (rest, heel lifts, PT, NSAIDS, cam walker immobilization, night splinting, local modalities) and had pre-treatment AOFAS scores of 52 (24–60). The PRP group had an average age of 51 (21–67) and had failed 5 months (3–26) of standard non-operative management (rest, heel lifts, PT, NSAIDS, cam walker immobilization, night splinting, local modalities) and had pre-treatment AOFAS scores of 37 (30–56). All patients were then immobilized fully weight bearing in a cam walker for 2 weeks, started on eccentric home exercises and allowed to return to normal activities as tolerated and without brace support. Post-treatment AOFAS scores were PRP 95 (84–100) and cortisone 81(60–90) at 3 months (CI 95% p< .0001), PRP 95 (86–100) and cortisone 81 (60–90) at 6 months (CI 95% p< .0001), and PRP 94 (86–100) and cortisone 58 (45–77) at 12 months (CI 95% p< .0001). Platelet rich plasma injection is more effective and durable than cortisone injection for the treatment of severe chronic plantar fasciitis refractory to traditional non-operative management.

Autologous injection of platelet rich plasma (PRP) stimulates healing process in degenerated tendons. The purpose of this study is to compare the functional outcome of lateral epicondylitis treated with PRP and steroid injection.

Tennis elbow patients who failed conservative medical therapy were included and were allocated randomly steroid group (n=70) and PRP group (n=63). Data were collected before procedure, at 4, 8, 12 weeks, 1 year and 2 years after procedure. The main outcome measures were visual analogue score, Mayo elbow performance score, DASH score and hand grip strength.

Successful treatment was defined as more than a 25% reduction in visual analogue score or DASH score and more than 75 score in Mayo elbow performance score. We observed that 35 of the 70 patients (50%) in corticosteroid group and 47 of the 63 patients (75%) in PRP group were successful, which was significantly different (p<.001), according to DASH score 37 of the 70 patients (53%) and 47 of the 63 patients (75%) in the PRP group were successful which was also significantly different (P = .005), Mayo elbow performance score was successful in 36 of the 70 patients (51%) in corticosteroid group and 49 of the 63 patients (78%) in PRP group. The improvement in hand grip strength of hand from 24.7kg (mean) 26kg in corticosteroid group and 23.5kg (mean) to 32.9kg (mean) in PRP group.

PRP injection for chronic lateral epicondylitis reduces pain, improve functionality and hand grip strength when compared to steroid injection.

Summary Statement

An autologous thrombin activated 3-fold PRP, mixed with a biphasic calcium phosphate at a 1mL:1cc ratio, is beneficial for early bone healing in older age sheep.

The February 2023 Research Roundup. 360. looks at: Clinical and epidemiological features of scaphoid fracture nonunion; Routine sterile glove and instrument change at the time of abdominal wound closure to prevent surgical site infection (ChEETAh); Characterization of genetic risk of end-stage knee osteoarthritis treated with total knee arthroplasty; Platelet-rich plasma or autologous blood injection for plantar fasciitis; Volume and outcomes of joint arthroplasty; The hazards of absolute belief in the p-value laid bare

Aims. Intra-articular (IA) injection may be used when treating hip osteoarthritis (OA). Common injections include steroids, hyaluronic acid (HA), local anaesthetic, and platelet-rich plasma (PRP). Network meta-analysis allows for comparisons between two or more treatment groups and uses direct and indirect comparisons between interventions. This network meta-analysis aims to compare the efficacy of various IA injections used in the management of hip OA with a follow-up of up to six months. Methods. This systematic review and network meta-analysis used a Bayesian random-effects model to evaluate the direct and indirect comparisons among all treatment options. PubMed, Web of Science, Clinicaltrial.gov, EMBASE, MEDLINE, and the Cochrane Library were searched from inception to February 2023. Randomized controlled trials (RCTs) which evaluate the efficacy of HA, PRP, local anaesthetic, steroid, steroid+anaesthetic, HA+PRP, and physiological saline injection as a placebo, for patients with hip OA were included. Results. In this meta-analysis of 16 RCTs with a total of 1,735 participants, steroid injection was found to be significantly more effective than placebo injection on reported pain at three months, but no significant difference was observed at six months. Furthermore, steroid injection was considerably more effective than placebo injection for functional outcomes at three months, while the combination of HA+PRP injection was substantially more effective at six months. Conclusion. Evidence suggests that steroid injection is more effective than saline injection for the treatment of hip joint pain, and restoration of functional outcomes. Cite this article: Bone Joint J 2024;106-B(6):532–539

The April 2023 Knee Roundup. 360. looks at: Does bariatric surgery reduce complications after total knee arthroplasty?; Mid-flexion stability in total knee arthroplasties implanted with kinematic alignment: posterior-stabilized versus medial-stabilized implants; Inflammatory response in robotic-arm-assisted versus conventional jig-based total knee arthroplasty; Journey II bicruciate stabilized (JII-BCS) and GENESIS II total knee arthroplasty: the CAPAbility, blinded, randomized controlled trial; Lifetime risk of revision and patient factors; Platelet-rich plasma use for hip and knee osteoarthritis in the USA; Where have the knee revisions gone?; Tibial component rotation in total knee arthroplasty: CT-based study of 1,351 tibiae

Aims. To determine whether platelet-rich plasma (PRP) injection improves outcomes two years after acute Achilles tendon rupture. Methods. A randomized multicentre two-arm parallel-group, participant- and assessor-blinded superiority trial was undertaken. Recruitment commenced on 28 July 2015 and two-year follow-up was completed in 21 October 2019. Participants were 230 adults aged 18 years and over, with acute Achilles tendon rupture managed with non-surgical treatment from 19 UK hospitals. Exclusions were insertion or musculotendinous junction injuries, major leg injury or deformity, diabetes, platelet or haematological disorder, medication with systemic corticosteroids, anticoagulation therapy treatment, and other contraindicating conditions. Participants were randomized via a central online system 1:1 to PRP or placebo injection. The main outcome measure was Achilles Tendon Rupture Score (ATRS) at two years via postal questionnaire. Other outcomes were pain, recovery goal attainment, and quality of life. Analysis was by intention-to-treat. Results. A total of 230 participants were randomized, 114 to PRP and 116 to placebo. Two-year questionnaires were sent to 216 participants who completed a six-month questionnaire. Overall, 182/216 participants (84%) completed the two-year questionnaire. Participants were aged a mean of 46 years (SD 13.0) and 25% were female (57/230). The majority of participants received the allocated intervention (219/229, 96%). Mean ATRS scores at two years were 82.2 (SD 18.3) in the PRP group (n = 85) and 83.8 (SD 16.0) in the placebo group (n = 92). There was no evidence of a difference in the ATRS at two years (adjusted mean difference -0.752, 95% confidence interval -5.523 to 4.020; p = 0.757) or in other secondary outcomes, and there were no re-ruptures between 24 weeks and two years. Conclusion. PRP injection did not improve patient-reported function or quality of life two years after acute Achilles tendon rupture compared with placebo. The evidence from this study indicates that PRP offers no patient benefit in the longer term for patients with acute Achilles tendon rupture. Cite this article: Bone Joint J 2022;104-B(11):1256–1265

The June 2024 Shoulder & Elbow Roundup. 360. looks at: Reverse versus anatomical total shoulder replacement for osteoarthritis? A UK national picture; Acute rehabilitation following traumatic anterior shoulder dislocation (ARTISAN): pragmatic, multicentre, randomized controlled trial; acid for rotator cuff repair: a systematic review and meta-analysis of randomized controlled trials; Metal or ceramic humeral head total shoulder arthroplasty: an analysis of data from the National Joint Registry; Platelet-rich plasma has better results for long-term functional improvement and pain relief for lateral epicondylitis: a systematic review and meta-analysis of randomized controlled trials; Quantitative fatty infiltration and 3D muscle volume after nonoperative treatment of symptomatic rotator cuff tears: a prospective MRI study of 79 patients; Locking plates for non-osteoporotic proximal humeral fractures in the long term; A systematic review of the treatment of primary acromioclavicular joint osteoarthritis

Various approaches have been implemented to enhance bone regeneration, including the utilization of autologous platelet-rich plasma and bone morphogenetic protein-2. The objective of this study was to evaluate the impact of Marburg Bone Bank-derived bone grafts in conjunction with platelet-rich plasma (PRP), recombinant human bone morphogenetic protein-2 (rhBMP-2), and zoledronic acid (ZA) on osteogenesis within rabbit bone defects. Methodology. Bone defects (5mm in diameter) were created in the femurs of 96 male rabbits. The animals were allocated into five groups: (1) bone graft + PRP (BG + PRP), (2) bone graft + 5μg rhBMP-2 (BG + rhBMP-2), (3) bone graft + 5μg ZA (BG + ZA), (4) bone graft + 10μg rhBMP-2 + 5μg ZA (BG + rhBMP-2 + ZA), and (5) bone graft (BG). Marburg Bone Bank-processed human femoral head allografts were utilized for bone grafting. The rabbits were euthanized at 14-, 30-, and 60-days post-surgery, and their femurs underwent histopathological and histomorphometric assessments. Results. Histomorphometric analysis revealed significantly enhanced de novo osteogenesis within the bone allografts in the BG + PRP and BG + rhBMP-2 groups compared to the BG, BG + ZA, and BG + rhBMP-2 + ZA groups at 14 and 30 days (p < 0.05). However, on day 60, the BG + rhBMP-2 group exhibited elevated osteoclastic activity (early resorption). The local co-administration of ZA with thermally treated grafts impeded both bone graft resorption and new bone formation within the bone defect across all time points. The addition of ZA to BG + rhBMP-2 resulted in diminished osteogenic activity compared to the BG + rhBMP-2 group (p < 0.000). Conclusion. The study findings indicated that the combination of PRP and rhBMP-2 with Marburg bone grafts facilitates early-stage osteogenesis in bone defect healing. Incorporating ZA into the thermally treated bone graft hinders both graft resorption and de novo bone formation

Aims. This study investigates the effects of intra-articular injection of adipose-derived mesenchymal stem cells (AdMSCs) and platelet-rich plasma (PRP) on lameness, pain, and quality of life in osteoarthritic canine patients. Methods. With informed owner consent, adipose tissue collected from adult dogs diagnosed with degenerative joint disease was enzymatically digested and cultured to passage 1. A small portion of cells (n = 4) surplus to clinical need were characterized using flow cytometry and tri-lineage differentiation. The impact and degree of osteoarthritis (OA) was assessed using the Liverpool Osteoarthritis in Dogs (LOAD) score, Modified Canine Osteoarthritis Staging Tool (mCOAST), kinetic gait analysis, and diagnostic imaging. Overall, 28 joints (25 dogs) were injected with autologous AdMSCs and PRP. The patients were followed up at two, four, eight, 12, and 24 weeks. Data were analyzed using two related-samples Wilcoxon signed-rank or Mann-Whitney U tests with statistical significance set at p < 0.05. Results. AdMSCs demonstrated stem cell-like characteristics. LOAD scores were significantly lower at week 4 compared with preinjection (p = 0.021). The mCOAST improved significantly after three months (p = 0.001) and six months (p = 0.001). Asymmmetry indices decreased from four weeks post-injection and remained significantly lower at six months (p = 0.025). Conclusion. These improvements in quality of life, reduction in pain on examination, and improved symmetry in dogs injected with AdMSCs and PRP support the effectiveness of this combined treatment for symptom modification in canine OA for six months. Cite this article: Bone Joint Res 2021;10(10):650–658

Platelet-rich plasma is a new inductive therapy which is being increasingly used for the treatment of the complications of bone healing, such as infection and nonunion. The activator for platelet-rich plasma is a mixture of thrombin and calcium chloride which produces a platelet-rich gel. We analysed the antibacterial effect of platelet-rich gel in vitro by using the platelet-rich plasma samples of 20 volunteers. In vitro laboratory susceptibility to platelet-rich gel was determined by the Kirby-Bauer disc-diffusion method. Baseline antimicrobial activity was assessed by measuring the zones of inhibition on agar plates coated with selected bacterial strains. Zones of inhibition produced by platelet-rich gel ranged between 6 mm and 24 mm (mean 9.83 mm) in diameter. Platelet-rich gel inhibited the growth of Staphylococcus aureus and was also active against Escherichia coli. There was no activity against Klebsiella pneumoniae, Enterococcus faecalis, and Pseudomonas aeruginosa. Moreover, platelet-rich gel seemed to induce the in vitro growth of Ps. aeruginosa, suggesting that it may cause an exacerbation of infections with this organism. We believe that a combination of the inductive and antimicrobial properties of platelet-rich gel can improve the treatment of infected delayed healing and nonunion

Biofabrication is a popular technique to produce personalized constructs for tissue engineering. In this study we combined laponite (Lap), gellan gum (GG) with platelet-rich plasma (PRP) aiming to enhance the endothelial regeneration through the synergistic effects of their individual properties. Laponite has the ability to form porous three-dimensional networks mimicking the extracellular matrix structure, and PRP delivery of growth factors stimulates the endothelial cell proliferation and migration, offering a composite bioink for cell growth and support. The sustained release of these growth factors from the GG-laponite-PRP composite material over time provides a continuous source of stimulation for the cells, leading to more effective tissue engineering strategies for endothelial tissue regeneration. Four blend compositions comprising 1% w/v GG and 0.5 or 1% w/v Lap and 25% v/v PRP were combined with Wharton jelly mesenchymal stem cells (WJ-MSCs) and bioprinted into vessel-like structures with an inner diameter of 3 mm and a wall thickness of 1 mm. Stress/strain analysis revealed the elastomeric properties of the hydrogels with Young modulus values of 10 MPa. Increasing the Lap concentration led to a non-significant decrease of swelling ratio from 93 to 91%. Live/dead assay revealed cell viability of at least 76%, with the 0.5%Lap-GG viability exceeding 99% on day 21. Gradual increase of glycosaminoglycans accumulation and collagen production indicate promotion of ECM formation. The expression and membranous localization of PECAM-1 from day 7 and the granular intracellular localization of vWF after 2 weeks demonstrate in vitro endothelial functionality. In vivo subcutaneous implantation indicated the absence of any adverse immunological reactions. The results reveal the expression of both vWF and PECAM-1 by WJ-MSCs entrapped in all four construct compositions with significantly higher expression of vWF in the presence of PRP

The August 2013 Research Roundup. 360 . looks at: passive smoking and bone substitutes; platelet-rich plasma and osteogenesis; plantar fasciitis and platelet-rich plasma: a match made in heaven?; MRSA decolonisation decreases infection rates; gums, bisphosphonates and orthopaedics; PRAISE and partner violence; blunt impact and post-traumatic OA; and IDEAL research and implants

Osteoarthritis (OA) is a degenerative disease that lacks regenerative treatment options. Current research focuses on mesenchymal stem cells (MSCs) and Platelet-Rich Plasma (PRP) as regenerative therapies, but extracellular vesicles (EVs) have shown to be more advantageous. This study compares the regenerative potential of human umbilical cord MSC-derived EVs (cEVs) and platelet-derived EVs (pEVs) in ex vivo and in vivo OA models. In the ex vivo study, OA conditions were induced in human cartilage explants, which were then treated either with pEVs or cEVs. Results showed a higher content of DNA and collagen in the pEVs group compared to control and cEVs groups, suggesting that pEVs could be a potential alternative to cEVs. In the in vivo study, an OA model was established in the knee joints of rats through MIA (monoiodoacetate) injection and then treated either with pEVs or cEVs. Results showed that pEVs-treated knee joints had better subchondral bone integrity and greater OA reversion, particularly in female rats, indicating that pEVs are a viable regeneration treatment for OA and outperform cEVs in terms of efficacy. Overall, the study demonstrates the potential of EVs as a regenerative treatment for OA, with pEVs showing promising results in both ex vivo and in vivo models. The use of pEVs in clinical practice could provide a faster path to translation due to the established use of platelet concentrates in therapeutics. However, further studies are needed to fully evaluate the potential of pEVs for OA treatment and to elucidate the mechanisms behind their regenerative effects. Acknowledgments: The authors thank Dr Fernando Hierro (UIB) for their technical contribution with TEM, Mª Trinidad García (UIB) for the access to radioactivity facilities, Aina Arbós (IUNICS) for her contribution in the histology staining, María Tortosa (IdISBa) for her assistance with the animal care and ADEMA School of Dentistry for the access to the cone beam computed tomography (CBCT). Funding: This research was funded by Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, co-funded by the ESF European Social Fund and the ERDF European Regional Development Fund (MS16/00124; CP16/00124), PROGRAMA JUNIOR del proyecto TALENT PLUS, construyendo SALUD, generando VALOR (JUNIOR01/18), financed by the sustainable tourism tax of the Balearic Islands; the Direcció General d'Investigació and Conselleria d'Investigació, Govern Balear (FPI/2046/2017); the Mecanisme de Recuperació i Resiliència, intended to execute research projects of «Noves polítiques públiques per a un mercat de treball dinàmic, resilient i inclusiu», collected in Pla de Recuperació, Transformació i Resiliència, financed by European Union-Next Generation EU and driven by SOIB and Conselleria de Fons Europeus, Universitat i Cultura i la Conselleria de Model Econòmic, Turisme i Treball (NG0421) and the grant SYN20/03 from IdISBa

Menisci are crucial structures for knee homeostasis: they provide increase of congruence between the articular surfaces of the distal femur and tibial plateau, bear loading, shock absorption, lubrication, and proprioception. After a meniscal lesion, the golden rule, now, is to save as much meniscus as possible: only the meniscus tissue which is identified as unrepairable should be excised and meniscal sutures find more and more indications. Several different methods have been proposed to improve meniscal healing. They include very basic techniques, such as needling, abrasion, trephination and gluing, or more complex methods, such as synovial flaps, meniscal wrapping, or the application of fibrin clots. Basic research of meniscal substitutes has also become very active in the last decades. The features needed for a meniscal scaffold are: promotion of cell migration, it should be biomimetic and biocompatible, it should resist forces applied and transmitted by the knee, it should slowly biodegrade and should be easy to handle and implant. Several materials have been tested, that can be divided into synthetic and biological. The first have the advantage to be manufactured with the desired shapes and sizes and with precise porosity dimension and biomechanical characteristics. To date, the most common polymers are polylactic acid (PGA); poly-(L)-lactic acid (PLLA); poly- (lactic-co-glycolic acid) (PLGA); polyurethane (PU); polyester carbon and polycaprolactone (PCL). The possible complications, more common in synthetic than natural polymers are poor cell adhesion and the possibility of developing a foreign body reaction or aseptic inflammation, leading to alter the joint architecture and consequently to worsen the functional outcomes. The biological materials that have been used over time are the periosteal tissue, the perichondrium, the small intestine submucosa (SIS), acellular porcine meniscal tissue, bacterial cellulose. Although these have a very high biocompatibility, some components are not suitable for tissue engineering as their conformation and mechanical properties cannot be modified. Collagen or proteoglycans are excellent candidates for meniscal engineering, as they maintain a high biocompatibility, they allow for the modification of the porosity texture and size and the adaptation to the patient meniscus shape. On the other hand, they have poor biomechanical characteristics and a more rapid degradation rate, compared to others, which could interfere with the complete replacement by the host tissue. An interesting alternative is represented by hydrogel scaffolds. Their semi-liquid nature allows for the generation of scaffolds with very precise geometries obtained from diagnostic images (i.e. MRI). Promising results have been reported with alginate and polyvinyl alcohol (PVA). Furthermore, hydrogel scaffolds can be enriched with growth factors, platelet-rich plasma (PRP) and Bone Marrow Aspirate Concentrate (BMAC). In recent years, several researchers have developed meniscal scaffolds combining different biomaterials, to optimize the mechanical and biological characteristics of each polymer. For example, biological polymers such as chitosan, collagen and gelatin allow for excellent cellular interactions, on the contrary synthetic polymers guarantee better biomechanical properties and greater reliability in the degradation time. Three-dimensional (3D) printing is a very interesting method for meniscus repair because it allows for a patient-specific customization of the scaffolds. The optimal scaffold should be characterized by many biophysical and biochemical properties as well as bioactivity to ensure an ECM-like microenvironment for cell survival and differentiation and restoration of the anatomical and mechanical properties of the native meniscus. The new technological advances in recent years, such as 3D bioprinting and mesenchymal stem cells management will probably lead to an acceleration in the design, development, and validation of new and effective meniscal substitutes

Aims. Platelet concentrates, like platelet-rich plasma (PRP) and platelet lysate (PL), are widely used in regenerative medicine, especially in bone regeneration. However, the lack of standard procedures and controls leads to high variability in the obtained results, limiting their regular clinical use. Here, we propose the use of platelet-derived extracellular vesicles (EVs) as an off-the-shelf alternative for PRP and PL for bone regeneration. In this article, we evaluate the effect of PL-derived EVs on the biocompatibility and differentiation of mesenchymal stromal cells (MSCs). Methods. EVs were obtained first by ultracentrifugation (UC) and then by size exclusion chromatography (SEC) from non-activated PL. EVs were characterized by transmission electron microscopy, nanoparticle tracking analysis, and the expression of CD9 and CD63 markers by western blot. The effect of the obtained EVs on osteoinduction was evaluated in vitro on human umbilical cord MSCs by messenger RNA (mRNA) expression analysis of bone markers, alkaline phosphatase activity (ALP), and calcium (Ca. 2+. ) content. Results. Osteogenic differentiation of MSCs was confirmed when treated with UC-isolated EVs. In order to disprove that the effect was due to co-isolated proteins, EVs were isolated by SEC. Purer EVs were obtained and proved to maintain the differentiation effect on MSCs and showed a dose-dependent response. Conclusion. PL-derived EVs present an osteogenic capability comparable to PL treatments, emerging as an alternative able to overcome PL and PRP limitations. Cite this article: Bone Joint Res 2020;9(10):667–674

Introduction and Objective. The early pro-inflammatory hematoma phase of bone healing is characterized by platelet activation followed by growth factor release. Bone marrow mesenchymal stromal cells (MSC) play a critical role in bone regeneration. However, the impact of the pro-inflammatory hematoma environment on the function of MSC is not fully understood. We here applied platelet-rich plasma (PRP) hydrogels to study how platelet-derived factors modulate functional properties of MSC in comparison to a non-inflammatory control environment simulated by fibrin (FBR) hydrogels. Materials and Methods. MSC were isolated from acetabular bone marrow of patients undergoing hip arthroplasty. PRP was collected from pooled apheresis thrombocyte concentrates. The phenotype of MSC was analyzed after encapsulation in hydrogels or exposure with platelet-derived factors with regards to gene expression changes, cell viability, extracellular vesicle (EV) release and immunomodulatory effects utilizing cellular and molecular, flow cytometry, RT-PCR, western blot and immunofluorescence stainings. Results. Our results showed that encapsulation of MSC in PRP induced changes in cell metabolism increasing lactate production and reducing mitochondria membrane potential. This was followed by significantly decreased mTOR phosphorylation and differential gene regulation. While PRP-released factors could support EV-biogenesis and immunoregulation-related gene expression, FBR hydrogel reduced CD63+ and CD81+ EV release by MSC. In co-cultures with mitogen stimulated PBMC, pre-exposure of MSC with PRP reduced the proliferation rate and frequency of peripheral blood CD4. +. and favored the persistence of FOXP3. +. regulatory T lymphocytes (32±4.7% compared to 9±2.3% in control co-cultures where MSC were exposed to FBR). Conclusions. Our data indicate that exposure of MSC with a hematoma environment causes metabolic adaptation of MSC followed by increased immune regulatory functions, which in turn might contribute to resolution of inflammation required for successful bone healing

Objectives. Platelet-rich plasma (PRP) is being used increasingly often in the clinical setting to treat tendon-related pathologies. Yet the optimal PRP preparations to promote tendon healing in different patient populations are poorly defined. Here, we sought to determine whether increasing the concentration of platelet-derived proteins within a derivative of PRP, platelet lysate (PL), enhances tenocyte proliferation and migration in vitro, and whether the mitogenic properties of PL change with donor age. Methods. Concentrated PLs from both young (< 50 years) and aged (> 50 years) donors were prepared by exposing pooled PRP to a series of freeze-thaw cycles followed by dilution in plasma, and the levels of several platelet-derived proteins were measured using multiplex immunoassay technology. Human tenocytes were cultured with PLs to simulate a clinically relevant PRP treatment range, and cell growth and migration were assessed using DNA quantitation and gap closure assays, respectively. Results. Platelet-derived protein levels increased alongside higher PL concentrations, and PLs from both age groups improved tenocyte proliferation relative to control conditions. However, PLs from aged donors yielded a dose-response relationship in tenocyte behaviour, with higher PL concentrations resulting in increased tenocyte proliferation and migration. Conversely, no significant differences in tenocyte behaviour were detected when increasing the concentration of PLs from younger donors. Conclusion. Higher PL concentrations, when prepared from the PRP of aged but not young donors, were more effective than lower PL concentrations at promoting tenocyte proliferation and migration in vitro. Cite this article: D. R. Berger, C. J. Centeno, N. J. Steinmetz. Platelet lysates from aged donors promote human tenocyte proliferation and migration in a concentration-dependent manner. Bone Joint Res 2019;8:32–40. DOI: 10.1302/2046-3758.81.BJR-2018-0164.R1

Aims. The success of anterior cruciate ligament reconstruction (ACLR) depends on osseointegration at the graft-tunnel interface and intra-articular ligamentization. Our aim was to conduct a systematic review of clinical and preclinical studies that evaluated biological augmentation of graft healing in ACLR. . Materials and Methods. In all, 1879 studies were identified across three databases. Following assessment against strict criteria, 112 studies were included (20 clinical studies; 92 animal studies). . Results. Seven categories of biological interventions were identified: growth factors, biomaterials, stem cells, gene therapy, autologous tissue, biophysical/environmental, and pharmaceuticals. The methodological quality of animal studies was moderate in 97%, but only 10% used clinically relevant outcome measures. The most interventions in clinical trials target the graft-tunnel interface and are applied intraoperatively. Platelet-rich plasma is the most studied intervention, but the clinical outcomes are mixed, and the methodological quality of studies was suboptimal. Other biological therapies investigated in clinical trials include: remnant-augmented ACLR; bone substitutes; calcium phosphate-hybridized grafts; extracorporeal shockwave therapy; and adult autologus non-cultivated stem cells. Conclusion. There is extensive preclinical research supporting the use of biological therapies to augment ACLR. Further clinical studies that meet the minimum standards of reporting are required to determine whether emerging biological strategies will provide tangible benefits in patients undergoing ACLR. Cite this article: Bone Joint J 2018;100-B:271–84

The June 2012 Research Roundup. 360. looks at: platelet-rich plasma; ageing, bone and mesenchymal stem cells; cytokines and the herniated intervertebral disc; ulcerative colitis, Crohn’s disease and anti-inflammatories; the effect of NSAIDs on bone healing; osteoporosis of the fractured hip; herbal medicine and recovery after acute muscle injury; and ultrasound and the time to fracture union

The April 2015 Shoulder & Elbow Roundup. 360 . looks at: Distal clavicular resection not indicated in cuff repair?; Platelet-rich plasma in rotator cuff repair; Radial head geometry: time to change?; Heterotopic ossification in elbow trauma; Another look at heterotopic ossification in the humerus; Triceps on for total elbow arthroplasty?; Predicting outcomes in rotator cuff repair; Deltoid fatty infiltration and reverse shoulder arthroplasty

Post-traumatic osteonecrosis of the femoral head (ONFH) is a major complication of femoral neck fractures that require numerous solutions. The purpose of the current study is to investigate the effects of platelet-rich plasma (PRP) incorporated autologous granular bones graft for the treatment of pre-collapse stages (ARCO stage II-III) of post-traumatic ONFH. A total of 46 patients were eligible and enrolled into the study. 24 patients were treated with core decompression and PRP incorporated autologous granular bones graft (treatment group: 9 females and 15 males, age range, 16–39 years), and 22 patients with core decompression and autologous granular bones graft (control group: 6 females and 16 males, age range, 18–42 years. During a minimum duration of follow-up of 36 months, multiple imaging techniques including X-ray and computed tomography (CT) scanning were used to evaluate the radiological results, and Harris hip score (HHS) and the visual analogue scale (VAS) were chosen to assess the clinical results. Both treatment group and control group had a significant improved HHS (P < 0.001). The minimum clinically important difference (MCID) for HHS was reached in 91.7% of treatment group and 68.2% of control group (P = 0.0449). HHS in treatment group was significantly higher than control group at the last follow-up (P = 0.0254). VAS score was significantly declined in treatment group when compared with control group (P = 0.0125). Successful clinical results were achieved in 21 of 24 patients (87.5%) in treatment group compared with 13 of 22 patients (59.1%) in control group (P = 0.0284). Successful radiological results were achieved in 19 of 24 patients (79.2%) in treatment group compared with 11 of 22 patients (50%) in control group (P = 0.0380). The survival rates using requirement for further hip surgery as an endpoint were higher in treatment group in comparison to control group (P = 0.0260). The PRP incorporated autologous granular bones graft is a safe and effective procedure for the treatment of pre-collapse stages (ARCO stage II-III) of post-traumatic ONFH

The December 2013 Shoulder & Elbow Roundup. 360 . looks at: Platelet-rich plasma; Arthroscopic treatment of sternoclavicular joint osteoarthritis; Synchronous arthrolysis and cuff repair; Arthroscopic arthrolysis; Regional blockade in the beach chair; Recurrent instability; Avoiding iatrogenic nerve injury in elbow arthroscopy; and Complex reconstruction of total elbow revisions

The April 2012 Research Roundup. 360 . looks at who is capable of being an arthroscopist, bupivacaine, triamcinolone and chondrotoxicity, reducing scarring in injured skeletal muscle, horny Goat Weed and the repair of osseous defects, platelet-derived growth factor and fracture healing, the importance of the reserve zone in a child’s growth plate, coping with advanced arthritis, hydroxyapatite and platelet-rich plasma for bone defects, and calcium phosphate and bone regeneration

Objectives. To conduct a pilot randomised controlled trial to evaluate the feasibility of conducting a larger trial to evaluate the difference in Victorian Institute of Sports Assessment-Achilles (VISA-A) scores at six months between patients with Achilles tendinopathy treated with a platelet-rich plasma (PRP) injection compared with an eccentric loading programme. Methods. Two groups of patients with mid-substance Achilles tendinopathy were randomised to receive a PRP injection or an eccentric loading programme. A total of 20 patients were randomised, with a mean age of 49 years (35 to 66). All outcome measures were recorded at baseline, six weeks, three months and six months. Results. The mean VISA-A score for the injection group at the primary endpoint of six months was 76.0 (95% confidence interval (CI) 58.3 to 93.7) and for the exercise group was 57.4 (95% CI 38.1 to 76.7). There was no statistically significant difference between these scores (p = 0.171), which was expected from such a pilot study. Conclusions. This pilot study has been key to providing data to inform a larger study and shows that the methodology is feasible. Cite this article: Bone Joint Res 2013;2:227–32

The April 2013 Research Roundup. 360 . looks at: when the ‘residency cake’ is done; steroids, stem cells and tendons; what exactly is osteoarthritis; platelet-rich plasma; CRPS; d-Dimer for DVT; reducing bacterial adhesion; and fin or limb?

Introduction. Nowadays, autologous platelet-rich plasma is used commonly in wound treatment. However, platelet gel, which was derived from allogeneic platelet-rich plasma (PRP) [1,2], has never been studied about efficacy in vivo or animal models. We aimed to determine efficacy of allogeneic platelet-gel on wound healing in rats by comparing with untreated, antibiotic-gel (Mupirocin 2%) treated and gel (sodium carboxymethylcellulose(NaCMC))-treated control. Methods. Fresh frozen plasma was centrifuged at 1200-G for 15 minutes to extract PRP which would be freeze-dried at −70°c, sterilized with gamma ray of Cobalt source 25 kGy and stored at −70°c. Then, processed freeze-dried PRP was mixed with gel base (NaCMC) as in form of allogeneic platelet-gel concentrated 30 mg/1g by sterilization process (table 1). Full-thickness of 6-mm-diameter skin punch biopsies were performed on 18 female Wistar rats which each rat had four wounds at back. Each wound was applied with untreated care, antibiotic-gel, NaCMC-gel and platelet-gel, respectively. Wound healing was studied from day 0–12. Animals were sacrificed with wound tissues removal on day 3, 7, 12 post-biopsy. Digital planimetric measurement device (VISITRAK, Smith and Nephew) was used in evaluation of total wound area on day 0, 3, 7, 12 post-biopsy. Histopathological changes of wound healing were studied, using 4-μm thickness section with haematoxylin-eosin (H&E) and Masson's trichrome-stain, under light microscope. Results. Platelet-gel reduced wound size more rapidly on day 3, 7 than other groups with statistical significance (p<0.05), although no statistically significant difference compared to antibiotic-treated wounds. Histological study confirmed earlier granulation forming and more collagen fibers in platelet-gel treated group when compared with others. discussion & Conclusions. Allogeneic platelet gel produced the satisfactory efficacy on acute wound healing in rat. This platelet gel needs further study in human for efficacy and safety that might be developed for using in acute wound treatment in the future

Aims

This study aimed to evaluate the effectiveness of the induced membrane technique for treating infected bone defects, and to explore the factors that might affect patient outcomes.

Rotator cuff tears are common in middle-aged and elderly patients. Despite advances in the surgical repair of rotator cuff tears, the rates of recurrent tear remain high. This may be due to the complexity of the tendons of the rotator cuff, which contributes to an inherently hostile healing environment. During the past 20 years, there has been an increased interest in the use of biologics to complement the healing environment in the shoulder, in order to improve rotator cuff healing and reduce the rate of recurrent tears. The aim of this review is to provide a summary of the current evidence for the use of forms of biological augmentation when repairing rotator cuff tears.

Cite this article: Bone Joint J 2024;106-B(9):978–985.

Aims

The primary aim of this study was to assess the feasibility of recruiting and retaining patients to a patient-blinded randomized controlled trial comparing corticosteroid injection (CSI) to autologous protein solution (APS) injection for the treatment of subacromial shoulder pain in a community care setting. The study focused on recruitment rates and retention of participants throughout, and collected data on the interventions’ safety and efficacy.

The Cochrane Collaboration has produced five new reviews relevant to bone and joint surgery since the publication of the last Cochrane Corner These reviews are relevant to a wide range of musculoskeletal specialists, and include reviews in Morton’s neuroma, scoliosis, vertebral fractures, carpal tunnel syndrome, and lower limb arthroplasty.

The February 2023 Hip & Pelvis Roundup³⁶⁰ looks at: Total hip arthroplasty or internal fixation for hip fracture?; Significant deterioration in quality of life and increased frailty in patients waiting more than six months for total hip or knee arthroplasty: a cross-sectional multicentre study; Long-term cognitive trajectory after total joint arthroplasty; Costal cartilage grafting for a large osteochondral lesion of the femoral head; Foley catheters not a problem in the short term; Revision hips still a mortality burden?; How to position implants with a robotic arm; Uncemented stems in hip fracture?

The December 2022 Hip & Pelvis Roundup³⁶⁰ looks at: Fix and replace: simultaneous fracture fixation and hip arthroplasty for acetabular fractures in older patients; Is the revision rate for femoral neck fracture lower for total hip arthroplasty than for hemiarthroplasty?; Femoral periprosthetic fractures: data from the COMPOSE cohort study; Dual-mobility cups and fracture of the femur; What’s the deal with outcomes for hip and knee arthroplasty outcomes internationally?; Osteochondral lesions of the femoral head: is costal cartilage the answer?

The August 2024 Wrist & Hand Roundup³⁶⁰ looks at: Methotrexate shows potential in reducing pain for hand osteoarthritis with synovitis; Circumferential casting versus plaster splinting in adult distal radius fractures: the CAST study findings; Surgery shows superior long-term success for Dupuytren contracture compared to needle fasciotomy and collagenase injection; Evolving trends in surgical management of wrist arthritis: a decade-long national analysis; Mid-term outcomes of three commonly used surgical reconstructions for scapholunate instability; SLAC and SNAC: what is the evidence for treatment?; Steroids for trapeziometacarpal osteoarthritis?; When is it safe to return to driving after distal radius fracture fixation? A prospective study.

Aims

This study compared patients who underwent arthroscopic repair of large to massive rotator cuff tears (LMRCTs) with isolated incomplete repair of the tear and patients with incomplete repair with biceps tendon augmentation. We aimed to evaluate the additional benefit on clinical outcomes and the capacity to lower the re-tear rate.

Aims

Knee osteoarthritis (OA) is characterized by a chronic inflammatory process involving multiple cytokine pathways, leading to articular cartilage degeneration. Intra-articular therapies using pharmaceutical or autologous anti-inflammatory factors offer potential non-surgical treatment options. Autologous protein solution (APS) is one such product that uses the patient’s blood to produce a concentrate of cells and anti-inflammatory cytokines. This study evaluated the effect of a specific APS intra-articular injection (nSTRIDE) on patient-reported outcome measures compared to saline in moderate knee OA.

Aims

Extracellular vesicles (EVs) are nanoparticles secreted by all cells, enriched in proteins, lipids, and nucleic acids related to cell-to-cell communication and vital components of cell-based therapies. Mesenchymal stromal cell (MSC)-derived EVs have been studied as an alternative for osteoarthritis (OA) treatment. However, their clinical translation is hindered by industrial and regulatory challenges. In contrast, platelet-derived EVs might reach clinics faster since platelet concentrates, such as platelet lysates (PL), are already used in therapeutics. Hence, we aimed to test the therapeutic potential of PL-derived extracellular vesicles (pEVs) as a new treatment for OA, which is a degenerative joint disease of articular cartilage and does not have any curative or regenerative treatment, by comparing its effects to those of human umbilical cord MSC-derived EVs (cEVs) on an ex vivo OA-induced model using human cartilage explants.

Aims

The purpose of this study was to explore a simple and effective method of preparing human acellular amniotic membrane (HAAM) scaffolds, and explore the effect of HAAM scaffolds with juvenile cartilage fragments (JCFs) on osteochondral defects.

There has been a marked increase in the number of hip arthroscopies performed over the past 16 years, primarily in the management of femoroacetabular impingement (FAI). Insights into the pathoanatomy of FAI, and high-level evidence supporting the clinical effectiveness of arthroscopy in the management of FAI, have fuelled this trend. Arthroscopic management of labral tears with repair may have superior results compared with debridement, and there is now emerging evidence to support reconstructive options where repair is not possible. In situations where an interportal capsulotomy is performed to facilitate access, data now support closure of the capsule in selective cases where there is an increased risk of postoperative instability. Preoperative planning is an integral component of bony corrective surgery in FAI, and this has evolved to include computer-planned resection. However, the benefit of this remains controversial. Hip instability is now widely accepted, and diagnostic criteria and treatment are becoming increasingly refined. Instability can also be present with FAI or develop as a result of FAI treatment. In this annotation, we outline major current controversies relating to decision-making in hip arthroscopy for FAI.

Cite this article: Bone Joint J 2022;104-B(5):532–540.

Summary Statement. This experimental study showed that platelet rich fibrin matrix can improve muscle regeneration and long-term vascularization without local adverse effects. Introduction. Even though muscle injuries are very common, few scientific data on their effective treatment exist. Growth Factors (GFs) may have a role in accelerating muscle repair processes and a currently available strategy for their delivery into the lesion site is the use of autologous platelet-rich plasma (PRP). The present study is focused on the use of Platelet Rich Fibrin Matrix (PRFM), as a source of GFs. Materials and Methods. Bilateral muscular lesions were created on the longissimus dorsi muscle of Wistar rats. One side of the lesion was filled with a PRFM while the contralateral was left untreated (controls). Animals were sacrificed at 5, 10, 40 and 60 days from surgery. Histological, immunohistochemical and histomorphometric analyses were performed to evaluate muscle regeneration, neovascularization, fibrosis and inflammation. The presence of metaplasic zones, calcifications and heterotopic ossification were also assessed. Results. PRFM treated muscles exhibited an improved muscular regeneration, an increase in neovascularization, and a slight reduction of fibrosis compared with controls. No differences were detected for inflammation. Metaplasia, ossification and heterotopic calcification were not detected. Conclusions. This preliminary morphological experimental study shows that PRFM use can improve muscle regeneration and long-term vascularization. Since autologous blood products are safe, PRFM may be a useful and handily product in clinical treatment of muscle injuries

During the therapy of infected pseudarthrosis and arthrodesis in which multiple autologous bone grafts did not result in osseous consolidation and in delayed osseous healing of transport stretches after completion of segmental transport in osteomyelitis patients without acute infection symptoms, mesenchymal stem cells were added to the treatment. This study demonstrates the mid- and long-term results in different application possibilities with good and poor results. The aim is to develop an algorithm in treating bone defects regarding the different biomaterials and implants that exist on the market. The indication to apply mesenchymal stem cells was the reconstruction of osseous lesions after chronic osteomyelitis, the treatment of pseudarthrosis and the support of osseous growth in segmental transports. Further indications were the absence of adequate amounts of autologous spongiosa, multiple previous operations, risk factors (diabetes, peripheral vascular disease, alcohol and nicotine abuse, etc.) as well as chronic wound healing failure. To obtain the mesenchymal stem cells, we employed two different systems from two companies. Both systems concentrate the mesenchymal stem cells after puncture and aspiration from the pelvic crest. The concentrated stem cells were either mixed with platelet-rich plasma and added to the autologous spongiosa or injected into the area of osseous regeneration after completion of segment transport. Since 2009, we have applied mesenchymal stem cells to 87patients. The treatment was performed in 73 cases of persisting pseudarthrosis after multiple bone grafts and in 14 cases of delayed osseous healing after segmental transport. The results were evaluated by continuous clinical and radiological examinations in our outpatient clinic. We found a great variety in our results with a mainly high rate of survival and healing in the autologous bone grafts with mesenchymal stem cells, resulting predominantly in stabilization of the pseudarthrosis. Furthermore a good osseous consolidation was documented in several cases with transport stretches of segmental transports. However we also had some frustrating results with all the well-known complications of septic surgery. Our experiences so far, have led to a distinguished therapy-algorithm including all the biomaterials and additives that are used in our hospital. Overall, the results demonstrate an advantage in the treatment with mesenchymal stem cells, espe-cially in problematic and difficult cases in combination with multiple pre-existing conditions. The use of mesenchymal stemcells must be included in a general concept regarding all treatment possibilities, it is, however, not a guarantee for successful therapy of osseous lesions after chronic osteomyelitis especially as a single toll mechanism

Purpose:. To examine the performance of a novel blood plasma-based bone putty for augmenting the treatment of open tibia fractures. The putty was manufactured from pooled blood plasma and contains a concentration of both plasma and platelet-derived regenerative factors. Based on clinical reports of the use of autologous platelet-rich plasma to treat injuries, we hypothesized that the putty would accelerate healing of fractures and surrounding soft tissues. Methods:. Two-arm, randomized controlled study including 20 treatment patients and 10 controls. Follow-up examinations occurred at 14, 30, 60, 90, 180, and 365 days. The product was provided in a syringe containing 3 cc of putty in a double-pouched, sterile box. The putty was placed at the fracture site during open fracture reduction and mechanical stabilization. Results:. Both treatment and control groups were well balanced with a mean age of 35. Seventy percent were Gustillo IIIA and IIIB injuries, 67% were active smokers, and 70% received external fixation. No adverse events related to the use of the putty were noted. The use of the putty significantly reduced infections at 90 days (p = 0.002), accelerated bone bridging at 90 and 180 days, and provided more rapid wound closure at 30 days. In the subset of patients with IIIA/IIIB injuries, the putty group demonstrated more significantly reduced infections (p = 0.0007), with accelerated bone healing and wound closure approaching statistical significance. There were statistically fewer adverse events with the putty (42.1%) compared to controls (80.0%). Conclusions:. The potential for using a concentration of natural plasma and platelet-derived regenerative factors to augment the healing of traumatic injuries makes this first-in-man study relevant and exciting. The putty performed as expected, promoting more rapid healing of both fractures and wounds. The dramatic reduction in infections was unanticipated and is likely related to antimicrobial peptides in plasma and platelets

From June 2003 we have elaborated a new procedure consisting in an osteoinductive-antibiotic gel, positioned on the spongiosametal surfaces of the implant. The gel contains five elements: Cancellous bone chips, Platelet-Rich Plasma, Bone marrow, Fibrin glue, Vancomycin and Tobramycin. Blood loss, operative time Hemoglobin drop values and clinical results were collected. Our procedure shows a quickly osteointegration of the implants without septic complications due to the local delivery of antibiotics. The procedure is safe and easy because includes only autologous factors without risks of disease transmission or immune response

The cause of elbow tendinosis is most likely a combination of mechanical overloading and abnormal microvascular responses. Numerous methods of treatment have been advocated. In this study, we evaluated the use of platelet-rich plasma (PRP) as a treatment for resistant epicondylitis. The rationale for using platelets is that they participate predominantly in the early inflammation phases and degranulation. They constitute a reservoir of critical growth factors and cytokines which when placed directly into the damaged tissue, may govern and regulate the tissue healing process. We looked at 25 patients (19 with lateral and 6 with medial) who failed to improve after physiotherapy, cortisone injections and application of epicondylar clasps and assessed the efficacy of platelet-rich plasma injections using Gravitational platelet separation system (GPS). The cohort of patients included over a period of three years had physiotherapy, stretches, epicondylar clasp and an average of 2.9steroid injections (1–6) before having a PRP injection. The mean patient age was 43 years ranging between 24 and 54. There were 11 men and 14 women. The study included 19 patients with lateral epicondylitis and 6 patients with symptoms on the medial side. The ratio between dominant and nondominant side was according to the literature: 76%. The quick DASH scores imroved by 14% on an average in the first 3 months and further 26% in the following 9 months. 4 patients needed reintervention, 3 lateral and 1 medial and had surgical release between 6 and 12 months. 2 of them had reinjections before surgery. No local infections except mild inflammation and no systemic effects were noted. Within the limitations of being a case series and limited follow-up PRP injections provided a safe and progressive benefit over a period of 1 year in refractory cases, providing a good nonoperative alternative

Aims

The aim of this study was to prepare a scoping review to investigate the use of biologic therapies in the treatment of musculoskeletal injuries in professional and Olympic athletes.

Purpose. Platelet-Rich Plasma (PRP), an autologous derivative of whole blood that contains a supraphysiological concentration of platelets and growth factors. Most published studies have investigated the effect of PRP-conditioned media on cell cultures. We are not aware of any study that has investigated whole PRP with its cellular components on human tissue cultures. This study aims to investigate the effect of PRP on cell migration from human Achilles tendon explants, and the subsequent cellular proliferative effects in culture. Methods. This is an in-vitro study on tendon explants obtained from Achilles tendon rupture patients. The samples were collected in sterile DMEM F12 solution then carefully cut into approximately 1–3mm. 3. sections. Tendon explants were cultured in three media types: 1. 100% PRP; 2. 50% PRP; and 3. 50% fetal calf serum (FCS). 1 and 2 were made up using DMEM F12 media (standard culture medium). Explants and cells were incubated at 37°c in 5% CO. 2. for 48 hours. Results. Images of the explanted tissue were taken using a Nikon TE300 microscope with Retiga CCD camera and cells around each explant were counted. Kruskal-Wallis statistical test showed that 100%PRP and 50%PRP cultured explants have significantly higher number of cells (p ≤0.002 and 0.028 respectively) when compared with 50%FCS cultured explants. Ziva ultrasensitive proliferation assay revealed that 100%PRP significantly increased cell proliferation. In addition, PicoGreen assay showed that DNA content of 100% PRP cultured cells were significantly higher than the control. The concentration of TGF-b1, VEGF, PDGF-AB and IGF-1 growth factors were significantly higher in PRP comparing to 50% FCS medium. Conclusion. Our findings show that whole PRP strongly affect the behaviour of human tenocytes, indicating that PRP may have potential role as an orthobiological agent in ruptured tendon treatments