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.

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.

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

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 June 2024 Shoulder & Elbow Roundup³⁶⁰ 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.

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

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

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

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

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.

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

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

The April 2023 Knee Roundup³⁶⁰ 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.

The February 2023 Research Roundup³⁶⁰ 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.

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. 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

Abstract

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.