Purpose. The recent emergence of autologous blood concentrates, such as platelet rich plasma (PRP), as a treatment option for patients with orthopaedic injuries has led to an extensive debate about their clinical benefit. Our objective was to determine the effectiveness of autologous blood concentrates compared with control therapy in improving pain in patients with orthopaedic bone and soft tissue injuries. Method. We conducted a systematic review of MEDLINE and EMBASE from 1996 and 1947, respectively, up to July 2010. Additional studies were identified by contacting experts, searching the bibliographies of the included studies as well as orthopaedic meeting archives. We included published and unpublished randomized controlled trials or prospective cohort studies that compared autologous blood concentrates with a control therapy in patients with an orthopaedic injury. Two reviewers, working in duplicate, abstracted data on study characteristics and protocol. Reviewers resolved disagreement by consensus. Results. We identified 18 randomized trials and nine prospective cohort studies. There was a lack of consistency in outcome measures across all studies. Four randomized controlled trials (N=275) and three prospective cohort studies (N=88) reported visual analog scale (VAS) scores when comparing platelet rich plasma with a control therapy across injuries to the acromion, lateral epicondyle, anterior cruciate ligament, patella, tibia and spine. There was no significant benefit for platelet rich plasma up to and including six months across randomized trial (standardized mean difference −0.35; 95% confidence interval, −0.98 to 0.28) or prospective cohort data (standardized mean difference −0.20; 95% confidence interval, −0.64 to 0.23). Conclusion. There is a lack of evidence to support the efficacy of platelet rich plasma and autologous blood concentrates as a treatment modality for orthopaedic bone and soft tissue injuries. The literature is further complicated by a lack of standardization in study protocols, platelet separation techniques, and outcome measures

Introduction and Objectives: Growth factors with osteoinductive capacity can be considered biomaterials with significant activity in repair and regeneration processes in live beings. We carried out a study of an isolated application of a component rich in platelets and growth factors, platelet rich plasma (PRP), in a bone defect,. Materials and Methods: We carried out an experimental controlled prospective bilaterally comparative study in 30 New Zealand rabbits, with 6 mm diameter defects in the proximal metaphysis of the tibia and diaphysis of the fibula. The animals were divided into 2 groups of 15 individuals that received platelet rich plasma (PRP) or plasma poor in platelets (ppp) in their right tibia and fibula. The left tibia and fibula were used as non-treated controls. X-rays, CT scans and histological studies were assessed at 8, 12 and 16 weeks. Results: The CT scans, bone mineral density and histological studies showed improvement in the group treated with plasma poor in platelets (ppp) without any significant differences. Repair processes took place through membranous ossification. On statistical assessment, no significant statistical difference between variables was found. Discussion and Conclusions: In our experimental study of bone defects in experimental animals we did not find that platelet rich plasma, substance or autologous compound, had any osteoinductive or osteopromoting capacity

Chronic Achilles tendonosis is a common but difficult condition to successfully treat. Platelet rich plasma (PRP), a concentrated bioactive component of autologous blood that is rich in cytokines and other growth factors, was examined in this study to assess its ability to promote healing in severe cases of Achilles ten-donosis resistant to traditional non-operative treatment paradigms. Twenty-seven patients (16 males 11 females) with an average age of 46 (36–66) and who had failed an average of 8 months (6–10) of standard non-operative management for Achilles tendonosis (rest, heel lifts, PT, NSAIDS, cam walker / cast immobilization, night splinting, local modalities) were prosepectively included in the study. All patients had pre-treament MRI and ultrasound studies and clinical scoring was completed using the AOFAS hindfoot scoring system. Patients were treated by injecting a single dose of 4 cc of unbuffered PRP under local anesthesia directly into the injured zone of the Achilles tendon using ultrasound probe guidance. All patients were then immobilized fully weight bearing in a cam walker for 48 hours and then allowed to return to normal activites as tolerated and without support. Pre-treatment AOFAS scores averaged 34 (26–60), all patients had MRI and ultrasound evidence of chronic tendonosis and 9/27 had partial tears of the Achilles. All patients were considering operative intervention due to clinical dissatisfaction. Post-treatment AOFAS scores improved to 84 (80–87), at 1 month, 87 (84–90), at 2 months, 88 (87–100) at 3 months, and 92 (90–100) at 6 months with resolution of abnormalities seen in 25/27 post treatment MRI and ultrasound studies. All patients except one were clinically satisfied with their clinical results and no complications were reported. This study suggests that platelet rich plasma can be effective in the treatment of severe achilles tendonosis refractory to traditional non-operative management

Chronic plantar fasciitis is a common but sometimes difficult condition to successfully treat. Platelet rich plasma (PRP), a concentrated bioactive component of autologous blood that is 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 block-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 then allowed to return to normal activities as tolerated and without support. Post-treatment AOFAS scores in the cortisone initially improved to 81(60–90) at 3 months but decreased to 74 (56–85) at 6 months. Post-treatment AOFAS scores in the PRP group improved to 95 (84–90) at 3 months and remained excellent at 94 (87–100) at 6 months follow-up. This study suggests that 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

Introduction. Rotator cuff tears remain a problem, with massive tears having a failure rate of repair reported of up to 60%, despite advances in surgical techniques. Tissue engineering techniques offers the possibility of regenerating damaged tendon tissue to a pre-injury state. We explore these techniques by implanting two novel tendon augmentation grafts with use of platelet rich plasma (PRP) in sheep. Methods. A total of 24 sheep were operated on, with the infraspinatus being surgically cut from its attachment to the humeral head. Each tendon was repaired using suture anchors and an interpositional implant according to 4 groups: (1) Empty control, (2) Novel collagen fibre implant with PRP (3) A novel collagen sponge implant (4) and the collagen sponge with PRP. The sheep were killed at 12 weeks and the implant site harvested and its histology evaluated. Results. Our findings showed that these novel grafts were well integrated into the tissue, with minimal inflammatory response. However, as expected, the material had not yet completely broken down. Our initial findings suggest that the combination of PRP with the collagen sponge best enhanced the repair of the tendon. Conclusion. Tissue engineered collagen graft hold great potential for the repair of tendons

Different conditions may lead to bone loss in bone infections. Septic non-unions, osteomyelitis, septic joint prosthesis are all conditions that may be associated with the need for bone grafts and/or of bone substitutes. The risk of infection recurrence makes, in these cases, particularly challenging the choice of the type of bone implant. The use of growth factors, eventually associated with autologous or homologous bone grafts or with bone substitutes, may be helpful in restoring the bone stock, allowing to fill large bone defects, once the infection is controlled. We present the preliminary results in 10 patients in which autologous Platelet Rich Plasma (PRP) has been used to treat large bone defect in two stage hip reconstruction (7 cases) and in previously infected non-unions (3 patients). At a minimum follow-up of 6 months (maximum 18 months) a significant new bone formation occurred at the site of PRP application in all the cases treated and no signs of infection recurrence are present at the time of writing. This is the first report on the short-term safety of use of PRP for the treatment of bone loss in previously infected bones in humans. The limited number of patients and the follow-up do not allow at the moment to drive any conclusion regarding the efficacy and safety in the long term, and the use of PRP with this indications should be limited to selected cases

Purpose. Platelet Rich Plasma (PRP) has been shown to have positive effect in tendon regeneration in in-vitro and limited in-vivo animal studies. We aim to study PRP use in acute Achilles tendon rupture (ATR) regeneration in a purposely designed clinical trial. Methods. This is a prospective double-arm patient-blinded randomized controlled trial. ATR patients were randomized into PRP treatment or control groups. Non-operatively treated patients received PRP or control injection in clinic. In operatively treated patients, PRP gel was applied in the ruptured gap during percutaneous repair. Standard rehabilitation protocol was used and patients were followed up for 24 weeks. ATR, VISA-A and FAOS scores were used as subjective outcome measures. Functional ultrasound Elastography (FUSE) was performed at each follow-up to assess the mechanical properties of tendons. PRP analysis and tendon needle-biopsy were performed to study the histological differences during healing in both groups. Results. 20 patients were recruited with mean age 37.5±8.8 (8males and 7 females). Rupture location was 4.8±2.1 cm from insertion. PRP platelet count 1044±320 × 1000/μL with average platelet CD62p activation 68.42±4.5%. Mixed linear regression analysis revealed PRP treated tendon achieved better ATR and VISA-A outcome scores (p<0.05). FAOS score analysis showed that PRP group had better pain, ADL and symptoms scores with significant difference apparent from week 3 onwards. Strain mapping using FUSE scan in 4 patients showed bigger harder tendons in PRP group. Analysis of the remaining patients is on the way. To achieve the desired statistical power in pragmatic settings, recruitment will continue in a multi-centre trial. Conclusion. Our preliminary findings show that PRP application in Achilles tendon rupture may lead to faster regeneration and return to function as supported by a combination of objective and subjective outcome measures

Background. We compared platelet rich plasma (PRP) injection to cortisone (40mg triamcinolone) injection in the treatment of chronic plantar fasciitis resistant to traditional nonoperative management. The aims were to compare early and long term efficacy of PRP to that of Steroid (3, 6 and 12 months after injection). Methods. 60 heels with intractable plantar fasciitis with failed conservative treatment were randomized to either PRP or Steroid injection. All patients were assessed with Roles-Maudsley (RM) Score, Visual Analogue Score (VAS) for pain and the American Orthopaedic Foot and Ankle Society (AOFAS) score. Data was collected prospectively on the cohort, pre-treatment, at 3, 6 and 12 months post injection. The mean scores of the two groups were compared using Student t test. Results. Pre-injection, the two groups were well matched with no statistically significant difference in the values. At 3 months, all three outcome scores in both groups had significantly improved from their pretreatment level with no significant difference between the groups (PRP: RM 3.7 to 2.0, VAS 8.3 to 3.5, AOFAS 58 to 84; Steroid: RM 3.6 to 1.9, VAS 8.3 to 2.8, AOFAS 57 to 86). At 6 months, improvement was maintained in both groups with no significant difference between groups (PRP: RM 2.1, VAS 3.7, AOFAS 89; Steroid: RM 2.2, VAS 3.3, and AOFAS 84). At 12 months, all outcome measures were significantly better for the PRP group as response in the steroid group had deteriorated (PRP: RM 1.9, VAS 3.3 and AOFAS 89; Steroid: RM 2.6, VAS 5.1 and AOFAS 77: p = 0.008, 0.02 and 0.002 respectively). Conclusions. PRP is better for the treatment of chronic plantar fasciitis as compared to steroid. It shows no statistical difference in effectiveness early on, but unlike steroid, its effectiveness does not wear off with time, making it more durable

Introduction: Platelet rich plasma (PRP) has been hypothesised to be of potential benefit to articular cartilage tissue engineering, through its release of autologous growth factors. The aim of this study was to ascertain whether the addition of thrombin is required to achieve platelet activation and sustained growth factor release in-vitro, when PRP is applied to a collagen based osteochondral scaffold. Methods: Collagen/glycosaminoglycan scaffolds were fashioned, to which equal combined volumes of test substances were added (n=3): 500μl PRP; 375μl PRP + 125μl autologous thrombin (3:1); 455μl PRP + 45μl bovine thrombin (10:1). One ml of DMEM/F12 medium was added to each scaffold and changed completely at 12/24 hours, and 3/10 days, following which release of TGF-β1, PDGF-AB and bFGF were measured using ELISA. Secondly, equal sized collagen/glycosaminoglycan and polylactide co-glycolide scaffolds were fashioned to which 500μl of PRP were added (n=3). Similar conditions were followed as previously except that only PDGF-AB was assayed. Results: A similar cumulative release profile of all growth factors was found over the 10 day period. An increase in growth factor release was seen in the PRP only group at all time points with PDGF-AB in particular reaching statistical significance at all time points (p< 0.006). These findings remained apparent when a correction for volume was made (p< 0.028) suggesting a particular role of the collagen in platelet activation. This was shown in the second experiment, in which a significantly increased cumulative volume of PDGF-AB was released from the collagen/glycosaminoglycan scaffold without thrombin activation (p< 0.04). Discussion: This study shows that collagen is a potent activator of platelets, requiring no further addition to achieve satisfactory growth factor release when applied clinically. These results suggest that if PRP is combined with polymer scaffolds, it should be activated with thrombin to achieve optimum growth factor release

Introduction: Platelet rich plasma (PRP) has been hypothesised to be of potential benefit to articular cartilage tissue engineering, through its release of autologous growth factors. The aim of this study was to ascertain whether the addition of thrombin is required to achieve platelet activation and sustained growth factor release in-vitro, when PRP is applied to a collagen based osteochondral scaffold. Methods: Collagen/glycosaminoglycan scaffolds were fashioned, to which equal combined volumes of test substances were added (n=3): 500μl PRP; 375μl PRP + 125μl autologous thrombin (3:1); 455μl PRP + 45μl bovine thrombin (10:1). One ml of DMEM/F12 medium was added to each scaffold and changed completely at 12/24 hours, and 3/10 days, following which release of TGF-β1, PDGF-AB and bFGF were measured using ELISA. Secondly, equal sized collagen/glycosaminogly-can and polylactide co-glycolide scaffolds were fashioned to which 500μl of PRP were added (n=3). Similar conditions were followed as previously except that only PDGF-AB was assayed. Results: A similar cumulative release profile of all growth factors was found over the 10 day period. An increase in growth factor release was seen in the PRP only group at all time points with PDGF-AB in particular reaching statistical significance at all time points (p< 0.006). These findings remained apparent when a correction for volume was made (p< 0.028) suggesting a particular role of the collagen in platelet activation. This was shown in the second experiment, in which a significantly increased cumulative volume of PDGF-AB was released from the collagen/glycosaminoglycan scaffold without thrombin activation (p< 0.04). Discussion: This study shows that collagen is a potent activator of platelets, requiring no further additive to achieve satisfactory growth factor release when applied clinically. These results suggest that if PRP is combined with polymer scaffolds, it should be activated with thrombin to achieve optimum growth factor release

Introduction: Platelet rich plasma (PRP) has been hypothesised to be of potential benefit to articular cartilage tissue engineering, through its release of autologous growth factors. The aim of this study was to ascertain whether the addition of thrombin is required to achieve platelet activation and sustained growth factor release in-vitro, when PRP is applied to a collagen based osteochondral scaffold. Methods: Collagen/glycosaminoglycan scaffolds were fashioned, to which equal combined volumes of test substances were added (n=3): 500μl PRP; 375μl PRP + 125μl autologous thrombin (3:1); 455μl PRP + 45μl bovine thrombin (10:1). One ml of DMEM/F12 medium was added to each scaffold and changed completely at 12/24 hours, and 3/10 days, following which release of TGF-β1, PDGF-AB and bFGF were measured using ELISA. Secondly, equal sized collagen/glycosaminogly-can and polylactide co-glycolide scaffolds were fashioned to which 500μl of PRP were added (n=3). Similar conditions were followed as previously except that only PDGF-AB was assayed. Results: A similar cumulative release profile of all growth factors was found over the 10 day period. Greater growth factor release was seen in the PRP only group at all time points with PDGF-AB in particular reaching statistical significance at all time points (p< 0.006). These findings remained apparent when a correction for volume was made (p< 0.028) suggesting a particular role of the collagen in platelet activation. This was shown in the second experiment, in which a significantly increased cumulative volume of PDGF-AB was released from the collagen/glycosaminoglycan scaffold without thrombin activation (p< 0.04). Discussion: This study shows that collagen is a potent activator of platelets, requiring no further addition to achieve satisfactory growth factor release when applied clinically. These results suggest that if PRP is combined with polylactide co-glycolide scaffolds, it should be activated with thrombin to achieve optimum growth factor release

Introduction: The results of treating chondral lesions with microfracture have been well documented. The lesion heals by fibrocartilage and the functional results tend to deteriorate through time. Hypothesis: The use of steroids an platelet rich plasma (PRP) as coadjuvants to microfracture for the treatment of full thickness chondral lesions improve the results of this marrow stimulating technique. Purpose: To macroscopically, histologically and molecularly evaluate the repair tissue generated after treating full thickness chondral lesions with microfracture and local steroids or PRP in an animal model. Materials: Experimental in-vivo study in 40 femoral condyles (FC) from New Zealand rabbits. Chondral lesions were induced in all the samples and divided into 4 groups:. Group 1: control, lesion left untreated. Group 2: microfracture. Group 3: microfracture + intraarticular betamethasone. Group 4: microfracture + PRP. Animals were sacrificed after 3 months and the samples were evaluated macroscopically, histologically (H and E, Toluidine Blue) and molecularly (RT-PCR for Col1 and Col2). The results were analyzed with ANOVA and Bonferroni tests (p< 0.05). Results: Macroscopy: the control group had no healing tissue. In all the other groups there was a variable presence of a fibrocartilaginous tissue without significant differences among groups. Histology: all the groups had the presence of fibrocartilage. Molecular analysis: all the groups had a significantly poorer Col2/Col1 relation when compared to normal hyaline cartilage, without significant difference among groups. Conclusions: The local use of betamethasone and PRP as coadjuvants to microfracture does not improve the macroscopical, histological and molecular results of the treatment of full thickness chondral lesions

Introduction and Objectives: patellar tendinopaty (or jumper’s knee) is a frequent problem that affects active young adults. In some cases the different conservative treatment options are innefective and surgical treatment is considered. The purpouse of this study is to determine if repeated intratendinous inyections of platelet rich plasma (PRP) are effective for the treatment of these refractary cases. Materials and Methods: Eight consecutive patients (4 males and 4 females, mean age 24+/−5,9) who presented refractary patellar tendinopathies were included. All patients had presented symptoms for at least 6 months and had recieved treatmet for at least 3 months. All patients had been subjected to activity limitation, physical therapy, NSAID’s and laser and ultrasound therapy. In 3 cases corticosteroid inyections had been used. The subjects were assesed before treatment and 3 months and one year later with a Visual Analoge pain Scale (0 to 100mm, VAS), the Victorian Institute of Sport Assessment Patellar tendinopathy assesment scale(VISA-P) and the Lysholm score. Treatment consisted of 3 infiltrations (one week apart) of 3 cm3 of PRP extracted from their own blood with the GPS. ®. system (Biomet, Warsaw, Indiana, U.S.A). The PRP was infiltrated at the level of the tender tendon and inmediately behind the tendon at the proximal tendinous insertion and 1 cm distal to it through a single cutaneous puncture. Results: Of the 8 patients, 7 presented a significant increase (more than 20 points) in the VISA-P score and 1 did not present any noticeable improvement. No complications related to the injections were observed. The VISA-P score increased from a pretreatment mean of 29 +/− 10.7 to 79 +/− 10.7 at one year (significant differences, p< 0.001). A similar decrease was observed in the VAS pain score (pretreatment values of 75+/−28 to one year values of 21+/−19). There were not significat differences in the Lysholm score. Conclusions: PRP seems to be a possible alternative to surgical treatment in refractary patellar tendinopathy

Meniscal cartilage provides joint stabilisation, load distribution, impact absorption and decreased friction in joints that have a complex movement such as the knee. If the meniscal cartilage degrades or is surgically removed, there is a strong probability, over time, of damage to the articular surface. The ability to regenerate damaged meniscal cartilage with an implanted device that replaces the biological equivalent would allow for joint stabilisation, robust movement and reduce the risk of damage to the articular cartilage. An implant with many of the characteristics of meniscus and with the ability to integrate correctly and firmly with the surrounding tissue, would be advantageous. Inclusion of Platelet Rich Plasma (PRP) into the scaffolds to provide a concentrated source of matrix proteins and autologous growth factors may further enhance the regenerative repair process. To investigate the suitability of the collagen scaffolds, addition of meniscal chondrocytes and or PRP was examined in vitro. Human meniscal chondrocyte cells were isolated, via collagenase digestion, from meniscal cartilage recovered from total knee replacement surgery. Meniscal chondrocytes were cultured in vitro to expand cell numbers. PRP was produced from volunteer's blood using a centrifuge and density based platelet recovery system. Release of Platelet Derived Growth Factor type AB (PDGF-AB) was measured by ELISA as an indicator of the behaviour of the peptide growth factor component. Combinations of scaffold, meniscal chondrocytes and PRP were tested for interaction, suitability and viability. Experiments so far have shown good biocompatibility, in vitro, as meniscal chondrocytes were able to grow within the range of scaffolds produced. Cell retention could be enhanced by addition of PRP to the scaffolds. PDGF-AB was released over 5 days from the scaffold and PRP combination. Further studies are in progress to derive relevant scaffold modifications and combinations for practical, robust, treatment strategies

Platelet Rich Plasma (PRP) has shown to be a general stimulation for repair and 1 year results showed promising success percentages. To determine the effectiveness of PRP compared with corticosteroid injections in patients with chronic lateral epicondylitis with a two-year follow-up. A double-blind randomized controlled trial was conducted between May 2006 and January 2008. The trial was conducted in two Dutch teaching hospitals. 100 patients with chronic lateral epicondylitis were randomly assigned to a leucocyte-enriched PRP group (n=51) or in the corticosteroid group (n=49). Randomization and allocation to the trial group were carried out by a central computer system. Patients received either a corticosteroid injection or an autologous platelet concentrate injection through a peppering needling technique. The primary analysis included Visual Analogue Scale (VAS) pain scores and Disabilities of the Arm, Shoulder, and Hand Outcome (DASH) scores. The PRP group was more often successfully treated than the corticosteroid group (p<.0001). Success was defined as a reduction of 25% on VAS or DASH scores without a re-intervention after 2 years. When baseline VAS and DASH scores were compared with the scores at 2 years follow-up, both groups significantly improved across time (intention-to-treat principle). However, the DASH scores of the corticosteroid group returned back to baseline levels, while the PRP significantly improved (as-treated principle). There were no complications related to the use of PRP. Treatment of patients with chronic lateral epicondylitis with PRP reduces pain and increases function significantly, exceeding the effect of corticosteroid injection even after a follow-up of two years. Future decisions for application of PRP for lateral epicondylitis should be confirmed by further follow-up from this trial and should take into account possible costs and harms as well as benefits

Introduction

The purpose of this study was to investigate whether combining PRP or concentrated bone marrow aspirate (CBMA) with a biphasic collagen/glycosaminoglycan (CG) scaffold would improve the outcome of the treatment of full thickness osteochondral defects in sheep.

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.

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. Methods. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews and Arksey and O’Malley frameworks were followed. A three-step search strategy identified relevant published primary and secondary studies, as well as grey literature. The identified studies were screened with criteria for inclusion comprising clinical studies evaluating the use of biologic therapies in professional and Olympic athletes, systematic reviews, consensus statements, and conference proceedings. Data were extracted using a standardized tool to form a descriptive analysis and a thematic summary. Results. A total of 202 studies were initially identified, and 35 met criteria for the scoping review; 33 (94.3%) were published within the last eight years, and 18 (51.4%) originated from the USA. Platelet rich plasma was the most studied biologic therapy, being evaluated in 33 (94.3%) studies. Ulnar collateral ligament and hamstring injuries were the conditions most studied (nine (25.7%) studies and seven (20.0%) studies, respectively). Athletes most frequently participated in baseball, soccer, and American football. Only two (5.7%) studies were level 1 evidence, with interpretation and comparison between studies limited by the variations in the injury profile, biologic preparations, and rehabilitation protocols. Conclusion. There is diverse use of biologic therapies in the management of musculoskeletal injuries in professional and Olympic athletes. There is currently insufficient high-level evidence to support the widespread use of biologic therapies in athletes. Further research priorities include the development of condition/pathology-specific preparations of biologic therapies, and of outcome measures and imaging modalities sufficiently sensitive to detect differences in outcomes, should they exist. Cite this article: Bone Joint J 2021;103-B(7):1189–1196

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. Methods. Patients with more than 6 months of MRI proven plantar fasciitis who had failed conservative management were invited to participate in this study. Patients were block randomised to either platelet rich plasma injection (intervention) or equivalent volume of normal saline (control). The techniques used for the injection and rehabilitation were standardised for both groups. The patient and independent assessor were blinded. Visual analogue scale for pain (VAS) and painDETECT were recorded pre-op and at 6 months. Results. Twenty-eight patients (19 females, mean age 50 years) were recruited, with 14 randomised to each arm. At 6 month follow-up, 8 patients (28.6%) were lost to follow-up. There was a significant change in VAS score from baseline to follow-up in both intervention (mean change 37.2, p = 0.008) and control (mean change 42.2, p = 0.003) groups. However there was no difference between the arms in terms of the change in VAS score from baseline to follow-up (p = 0.183). There was no correlation between pre-op PainDETECT score and change in VAS. Conclusion. This pilot study has failed to show a significant benefit of platelet rich plasma compared to saline injection, although both treatments have shown a significant improvement in symptoms. This may be due to the needling effect of injections. A larger study is required to demonstrate a meaningful change. Loss to follow in this patient group should be considered

Aims. For cementless implants, stability is initially attained by an interference fit into the bone and osteo-integration may be encouraged by coating the implant with bioactive substances. Blood based autologous glue provides an easy, cost-effective way of obtaining high concentrations of growth factors for tissue healing and regeneration with the intention of spraying it onto the implant surface during surgery. The aim of this study was to incorporate nucleated cells from autologous bone marrow (BM) aspirate into gels made from the patient’s own blood, and to investigate the effects of incorporating three different concentrations of platelet rich plasma (PRP) on the proliferation and viability of the cells in the gel. Methods. The autologous blood glue (ABG) that constituted 1.25, 2.5, and 5 times concentration PRP were made with and without equal volumes of BM nucleated cells. Proliferation, morphology, and viability of the cells in the glue was measured at days 7 and 14 and compared to cells seeded in fibrin glue. Results. Overall, 2.5 times concentration of PRP in ABG was capable of supporting the maximum growth of cells isolated from the BM aspirate and maintain their characteristics. Irrespective of PRP concentration, cells in ABG had statistically significantly higher viability compared to cells in fibrin glue. Conclusion. In vitro this novel autologous gel is more capable of supporting the growth of cells in its structure for up to 14 days, compared to commercially available fibrin-based sealants, and this difference was statistically significant. Cite this article: Bone Joint Res 2020;9(7):402–411

Rotator cuff tendon healing has proven to be a substantial clinical challenge. There is significant interest in finding biologic augmentation methods to improve this healing process. Two currently available products include platelet rich plasma/platelet rich fibrin matrix and several commercially available extra cellular matrix (ECM) patches. Platelet rich plasma is a sample of an autologous blood which has been centrifuged to a concentration of platelets three to four times that of normal. Platelets contain multiple growth factors, many of which have been shown to be involved in all phases in tendon healing. An alternative is platelet rich fibrin matrix. This forms a fibrin matrix with the platelets embedded within. Growth factors are subsequently released as the fibrin is reabsorbed. There are only a few studies which look at the effectiveness of platelet rich plasma and fibrin matrix. Overall, there is no strong evidence to support its routine use in the setting of rotator cuff repair. Extra cellular matrix patches are used to reinforce the strength of the repair and offload the tendon. They also provide the potential to form a scaffold for new growth and differentiation and may at some point be a delivery vehicle for cells and growth factors. There are currently two prospective randomised studies evaluating ECM patches – one showed that the patch studied was actually harmful to repair and the second suggested there was some benefit in larger tears. While there is not a lot of strong evidence to support routine use, further research and development is necessary to maximise this strategy

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.

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. Methods. Forty consecutive age, sex and BMI-matched patients of osteonecrosis were enrolled for this prospective randomized comparative double blinded clinical study. 19 patients belonged to intervention group (PRP with Core decompression) and 21 to control (Core decompression) group. 8ml of autologous PRP was injected into channels alongwith Calcium Chloride (4:1) after core decompression. Patients were assessed for outcome measures by pain score, functional and Harris Hip scores, Modified Kerboul angle (combined necrotic angle) in MRI. Patients were followed up after 6, 24 weeks and final follow up (mean 10.33 months). Results. There was statistically significant difference in pain score in two groups at different follow ups (p: 0.002, 0.00; 0.001). The difference in function scores in two groups was statistically significant (p: 0.001). There was statistically significant difference in Harris Hip score in two groups at different follow ups (p: 0.021, 0.001; 0.003). Mean increase in modified Kerboul angle in group A was 11.32 (SD±13.00) and in group it was 18.33 (±14.347). 6 (24%) hips in group A and 12 (42%) hips in group B had progression of disease upto final follow up. Conclusions. Core decompression augmented with platelet rich plasma is effective in providing pain relief, improving the functional status and delaying or cessation of progression in early stage of osteonecrosis of hip

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.

Disease modifying approaches are commonly applied in OA patients. An aging society with better life expectancies is increasing in Europe and the globe. Orthobiologics cover intraarticular hyaluronan injections and also cellular therapies. Cellular therapies range from platelet rich plasma (PRP) applications to exosomes. Short term follow-up of limited number of patients revealed favorable results in clinical cellular therapies. Most of these studies evaluated decrease of pain and increase in function. Recent basic science studies focused on the action mechanism of orthobiologic therapies however patient perspective is less studied. Our research team has recently performed a qualitative study on the patient perspective of hyaluronan injection of the knee joint. Findings of that study will be shared and future patient knowledge based options on orthobiologics will be discussed

Introduction. Massive rotator cuff repairs have up to 60% failure rate and repair of a chronic repair can have up to 40% failure rate. With this in mind, new methodologies are being to being developed to overcome this problem. The use of tendon augmentation grafts is one of them. Prior attempts have shown equivocal or poorer outcomes to control repairs. Aims and objectives: The specific aim of these expereiments was to test how well ovine tendon cells would take to a specific biological augmentation graft (Ligamimetic), and wheter tissue engineering techniques would enhance this. Method. Tendon cells harvested from ovine tendons will be cultured, exposed to the tendon augmentation graft, and analysed to see how well it takes to the tendon cells. We have conducted a 21 day experiment, sampling at days 7, 14, and 21. The experiment will look in sheep tendon cells:1. Platelet rich plasma: A comparison of the effects of platelet rich plasma to cell adherence, cell proliferation, and collagen production. Mesenchymal stem cell: A comparison of the effects of mesenchymal stem cells to the material on cell adherence, cell proliferation, and collagen production. Results. Our results show that the ovine tendon cells do take to the tendon augmentation graft, and are able to proliferate. We will present DAPI stainings, DNA and collagen turnover, with Westin blotting results. Results show that the addition of PRP had increased the cell adherence, cell proliferation, and collagen production. These effects were not seen with the mesenchymal stem cells. Conclusion. These experiments have shown our novel collagen scaffold augmentation graft has allowed cells to proliferate on it. Tissue engineered techniques also enhance cell proliferation, and has the potential to enhance cell repair

Degenerative disc disease, associated to low back pain, afflicts more than 50% of humans, and represents a major healthcare problem, especially for the pathology initiation. Current treatments range from conservative strategies to more invasive surgical techniques, such as disc removal and vertebral fusion. In the Intervertebral Disease (IVD) the nucleus pulposus (NP) degeneration is a key factor for the pathology initiation. Several tissue engineering approaches aiming to restore the appropriate NP cell (NPCs) and matrix content, were attempted by using adult stromal cells either from bone marrow or adipose tissue, chondrocytes, notochordal cells and more recently also pluripotent stem cells. However, none was fully satisfactory since the NP acid and a-vascularized environment appeared averse to the implanted heterologous cells. Several studies demonstrated the efficacy of platelet derivatives such as platelet rich plasma (PRP) in promoting the regeneration of connective tissues. We investigated the efficacy of PRP on NPCs proliferation and differentiation with the goal to propose the direct stimulation of resident cells (stimulation of endogenous cells – less invasive surgical procedure) or the implantation of NPCs expanded in vitro in the presence of PRP as therapeutic agents in IVD degeneration. NPCs were isolated from small fragments of NP explants, cultivated in medium supplemented with PRP or FCS (standard condition control) and characterized by FACS analysis for the expression of the typical mesenchymal stem cells markers CD34, CD44, CD45, CD73, CD90 and CD105. NPCs cultured in PL showed a phenotypic profile like the cells cultured in FCS. However, compared to NPCs expanded in the presence of FCS, NPCs expanded in PRP showed a much better proliferation and differentiation capacity. NPCs differentiation was evaluated by the cell ability to produce an organized metachromatic cartilaginous matrix, confirmed by the positive immunohistochemical staining for chondrogenic markers

The use of platelet-leukocyte gel (PLG), made from platelet rich plasma, to stimulate bone formation and wound healing has been investigated extensively. As leukocytes play an important role in the innate host-defence, we hypothesised that PLG might also have antimicrobial properties. The purpose of this study was to investigate the antimicrobial activity of PLG against Staphylococcus aureus in an in vitro experiment. To determine the contribution of myeloperoxidase (MPO), present in leukocytes, in this process, MPO release was measured. Platelet rich plasma (PRP) was prepared from whole blood of 6 donors. In this process platelet poor plasma (PPP) was obtained as well. PLG was prepared by mixing PRP with either autologous (PLG-AT) or bovine thrombin (PLG-BT). The antimicrobial activity of PLG-AT, PLG-BT, PRP and PPP was determined in a bacterial kill assay, containing 1x106 CFU/ml of Staphylococcus aureus, during a 24-hour period. MPO release was measured by ELISA. Cultures showed a rapid decrease in the number of bacteria in the presence of both PLG-AT and PLG-BT, which was maximal between 4 and 8 hours, to approximately 1% of the bacteria in controls. Also PRP and PPP induced a statistically significant bacterial kill, but the effect of PLG-AT was the largest (p=0.093 vs. PLG-BT; p=0.004 vs. PRP and p< 0.001 vs. PPP). PLG-AT, PLG-BT and PRP showed a comparable, gradually increasing MPO release for 8 to 12 hours. Some MPO was also measured in the PPP samples. No correlation between MPO release and bacterial kill could be found. PLG appears to have potent antimicrobial capacity, but the role of MPO in this activity is questionable. PLG might represent a useful strategy against postoperative infections. Further research should investigate its antimicrobial capacity in the in vivo situation

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

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. Methods. In a placebo-controlled, participant- and assessor-blinded, trial at 19 NHS hospitals we randomly assigned 230 adults starting acute Achilles rupture non-surgical management to PRP injection or dry-needle insertion (placebo) to the rupture gap under local anaesthetic. Patients with confounding or contraindicated concurrent medical conditions were excluded. The primary outcome was muscle-tendon function, assessed by the limb symmetry index (LSI, uninjured limb/injured limb × 100, higher scores better) of the work (Joules) performed during the heel-rise endurance test at 24 weeks. Secondary outcomes were: Achilles Tendon Rupture Score (ATRS, 0–100, higher scores better), quality of life (SF-12), pain, and goal attainment. Trial registration: ISRCTN54992179. Results. Participants were aged mean 46 years and 57 (25%) were female. 103/114 (90%) of the PRP group and all (n=116) in the placebo group received allocated treatment. At 24 weeks, mean LSI was 34.4 for the PRP group and 38.8 for placebo (adjusted mean difference −4.4 95% CI −11.2 to 2.5, n=201) and ATRS was mean 65.2 PRP vs 65.8 (adjusted mean difference −0.6, 95% CI −4.9 to 3.7, n=224). There were no differences between groups in the other secondary outcomes. Conclusion. We found no evidence of PRP efficacy for improving muscle-tendon function or patient-reported recovery after acute Achilles tendon rupture. Our findings challenge the increasing global use of PRP for acute tendon injury and indicate that robust evaluations are required in other applications

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. Study design. Randomised multi-centre two-arm parallel-group, participant- and assessor-blinded, superiority trial. Methods. Adults with acute ATR managed non-surgically were recruited in 19 UK hospitals from 2015 to 2019. Exclusions were insertion or musculotendinous injuries, leg injury or deformity, diabetes, haematological disorder, corticosteroids and anticoagulation therapy. Participants were randomised via an online system 1:1 to PRP or placebo. Primary outcome was Achilles Tendon Rupture Score (ATRS) at two-years. Secondary outcomes were pain, Patient-Specific Functional Scale (PSFS), SF-12 and re-rupture. Assessors were blinded. Intention-to-treat and Compliance Average Causal effects (CACE) analyses were carried out. Consistency of effects across subgroups age, BMI, smoking and gender were assessed using Forest plots. Pearson's correlation was used to explore ATRS correlation with blood and growth factors. Results. 216/230 (94%) participants completed the 6-months follow-up were contacted. 182/216 (84%) completed the two-year follow-up. Participants were aged mean 46 (SD 13.0), 57 female/159 male. 96% received the allocated intervention. Two-years ATRS scores 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 two-years ATRS (adjusted-mean difference −0.752 95%CI −5.523 to 4.020, p=0.757), or in any secondary outcome, and no re-rupture between at two-years. Neither PRP cellular or growth factors correlated with the two-year ATRS. Conclusion. PRP did not improve patient-reported function or quality of life two-years after acute Achilles tendon rupture, compared with placebo, indicating that PRP offers no patient benefit in the longer term

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)

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.

Abstract. Background. Lateral and medial epicondylitis, more commonly known as Tennis and Golfer's elbow, can cause chronic pain and significant functional impairment in working-age patients. For patients with refractory epicondylitis, platelet rich plasma (PRP) of which ACP is a type, is commonly used as an alternative to surgical intervention, but its efficacy is unproven. Objective. To assess the mid-term outcomes of ultrasound guided ACP injections for patients with refractory epicondylitis who have failed conventional conservative treatment. Methods. 77 patients who were treated with PRP for refractory epicondylitis were included in the study. The mean age of patients was 50.3 years (range 36–70), with 30% men and 70% women. The Oxford Elbow Score (OES) and progression to surgery were used to assess the mid-term outcomes. Results. The mean follow up duration was 2.1 years (range 1.0 – 4.2). Post-procedure OES was recorded for thirty-three patients, of these, thirty-one patients (94.0%) demonstrated an improvement in their OES at mid-term follow-up compared to their pre-op score. The mean change in OES was +16 (range −7 to +34), 81.8% exhibited a minimally important change (MIC) in OES of greater than 8.2 points. Of all seventy-seven patients, seventeen (22.1%) underwent open release and twenty-seven (35.1%) patients were lost to follow up. Conclusion. Ultrasound guided ACP injections can be an effective treatment for refractory epicondylitis and is likely to prevent the need for surgery. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

The goal of surgery for osteochondral lesions is to regenerate the damaged cartilage with ideally hyaline cartilage. The current gold standard treatment is bone marrow stimulation (BMS) by microfracture. In reality however BMS typically results in the generation of fibrocartilage. Orthobiologics including bone marrow aspirate, platelet rich plasma and hyaluronic acid products have been shown to promote cartilage healing and potentially increase the formation of hyaline cartilage in treated lesions. However the role of these products, the timing of their administration and frequency of application are still not clearly defined and their routine use is still not recommended. These issues and future directions for research and future clinical application will be discussed

Biologic supplementation and augmentation techniques have become popular in recent years. There has been considerable media attention regarding professional athletes and celebrities who have traveled around the world to receive treatments using proprietary cocktails of platelet rich plasma, bone marrow aspirate concentrates, extracellular matrix, adipose-derived stem cells, human as well as xenograft derived collagen implants and protein supplements among other components. Unfortunately, the medical evidence regarding these treatments has often been inconsistent, inadequate with respect to levels of evidence with a dearth of mid- and long-term data to guide our treatments. This presentation will review the data available regarding the treatment of rotator cuff tendinosis, partial thickness rotator cuff tears, full thickness rotator cuff tears and osteoarthritis of the glenohumeral joint. Unfortunately, there are more questions than answers regarding the use of biologics

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

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.

Arthrosis of the hip joint can be a significant source of pain and dysfunction. While hip replacement surgery has emerged as the gold standard for the treatment of end stage coxarthrosis, there are several non-arthroplasty management options that can help patients with mild and moderate hip arthritis. Therefore, the purpose of this paper is to review early prophylactic interventions that may help defer or avoid hip arthroplasty. Nonoperative management for the symptomatic hip involves minimizing joint inflammation and maximizing joint mobility through intra-articular joint injections and exercise therapy. While weight loss, activity modifications, and low impact exercises is generally recommended for patients with arthritis, the effects of these modalities on joint strength and mobility are highly variable. Intra-articular steroid injections tended to offer reliable short-term pain relief (3–4 weeks) but provided unreliable long-term efficacy. Additionally, injections of hyaluronic acid do not appear to provide improved pain relief compared to other modalities. Finally, platelet rich plasma injections do not perform better than HA injections for patients with moderate hip joint arthrosis. Primary hip joint arthrosis is rare, and therefore treatment such as peri-acetabular osteotomies, surgical dislocations, and hip arthroscopy and related procedures are aimed to minimise symptoms but potentially aim to alter the natural history of hip diseases. The state of the articular cartilage at the time of surgery is critical to the success or failure of any joint preservation procedures. Lech et al. reported in a series of dysplastic patients undergoing periacetabular osteotomies that one third of hips survived 30 years without progression of arthritis or conversion to THA. Similarly, surgical dislocation of the hip, while effective for treatment of femoroacetabular impingement, carries a high re-operation rate at 7 years follow up. Finally, as the prevalence of hip arthroscopic procedures continues to rise, it is important to recognise that failure to address the underlying structural pathologies can lead to failure and rapid joint destruction. In summary, several treatment modalities are available for the management of hip pain and dysfunction in patients with a preserved joint space. While joint preservation procedures can help improve pain and function, they rarely alter the natural history of hip disease. The status of the articular cartilage at the time of surgery is the most important predictor of treatment success or failure

A common situation presenting to the orthopaedic surgeon today is a worn acetabular liner with substantial acetabular and pelvic osteolysis. The surgeon has many options for dealing with osteolytic defects. These include allograft, calcium based substitutes, demineralised bone matrix, or combinations of these options with or without addition of platelet rich plasma. To date there are no clinical studies to determine the efficacy of using bone-stimulating materials in osteolytic defects at the time of revision surgery and there are surprisingly few studies demonstrating the clinical efficacy of these treatment options. Even when radiographs appear to demonstrate incorporation of graft material CT studies have shown that incorporation is incomplete. The surgeon, in choosing a graft material for a surgical procedure must take into account the efficacy, safety, cost and convenience of that material. Cite this article: Bone Joint J 2014;96-B (11 Suppl A):70–2

There are a number of different non-operative management options for patients with a painful knee secondary to osteoarthritis (OA). In 2013 the American Academy of Orthopaedic Surgeons developed an evidence-based clinical practice guideline addressing treatment of osteoarthritis of the knee. Strength of recommendations were designated as strong, moderate and inconclusive. Strong recommendations included: self-management program, NSAIDs or tramadol and no acupuncture, no glucosamine and chondroitin sulfate and no hyaluronic acid. The “No” recommendations for hyaluronic acid and glucosamine and chondroitin sulfate were quite controversial because orthopaedic surgeons argued that some of their patients benefited from these treatments. Moderate strength recommendations included weight loss, lateral wedge insoles and needle lavage. The evidence-based data was inconclusive with respect to valgus force unloading brace, manual physical therapy, acetaminophen, opioids and pain patches. The effectiveness of corticosteroid and platelet rich plasma (PRP) injections were also inconclusive. Unloader braces are available to decrease pressure on the involved compartment. There is data showing that these braces can be effective for some patients. However, there are concerns with patient compliance because of poor fit and discomfort. These braces seemed to be tolerated best when used for sports activities in patients with medial compartment arthritis. Oral anti-inflammatory agents are effective in relieving pain and are a good first line agent for patients with OA. There is significant interest in the use of PRP injections for management of patients with knee OA particularly when patients have already received a steroid and/or a hyaluronic acid injection. To date there are no appropriately powered multi-centered randomised trials demonstrating that PRP is effective in decreasing pain and function in knee OA. However, there are some studies that suggest PRP can be helpful for patients with OA. Further studies to determine the indications for PRP injections are necessary. PRP injections are not covered by insurance in the United States. In summary, the management of patients with painful OA of the knee needs to be individualised based on patient symptoms and expectations. Non-operative management can be effective in limiting pain and enhancing function

Following the recognition of platelet rich plasma (PRP) as an interventional procedure by NICE, patients who had failed standard conservative treatment for chronic elbow tendinitis and referred for surgery were recruited prospectively into a PRP injection study. 52 patients at Torbay Hospital, Devon, UK received PRP injections in 18 months and 37 had a minimum of 6 months follow up. The outcomes in these patients are summarised. There were 16 males and 21 females. 30 had tennis elbow and 7 had golfers elbow. All patients had their symptoms for a minimum of 6 months and had failed to improve with standard conservative treatment. 2 had a failed outcome from previous tennis elbow release surgery. The PRP injections were carried out under ultrasound guidance after correlating the tender spot with neovascularisation on flow Doppler. 31 patients had a single injection; the other 21 patients had 2 injections. Quick DASH score and patients own self-satisfaction was used to measure outcome. 18 patients (48%) were discharged by 6 months. DASH score worsened in 7 patients (19%) and 2 of these patients opted to have surgery, which had no benefit either. No complications were observed with the use of PRP. Overall, by using PRP injections, surgery was avoided in 35 patients (95%) at 18 months and nearly half of the patients were discharged from follow up by 6 months

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

The incorporation of platelet rich plasma (PRP) in the treatment of various musculoskeletal conditions has increased exponentially over the past decade. While described most often as an augment or treatment for tendinopathies and acute tendon injuries, more recently, PRP has been described as an adjunct to arthroplasty procedures, mostly with respect to knee arthroplasty. In the shoulder, only a single study has been published, in which Zavadil and colleagues performed a randomised study of 40 patients undergoing total shoulder arthroplasty undergoing either treatment with autologous platelet gel and platelet poor plasma (n=20) or undergoing no biologic treatment (control group, n=20). The authors noted that the treatment group had significantly lower pain scores, less pain medication requirements, and improved internal rotation when compared to controls; in addition, there were no significant differences in post-operative (compared to pre-operative) hemoglobin levels or length of stay. The vast majority of arthroplasty studies discussing PRP analyze the impact of treatment on wound healing, post-operative pain, post-operative range of motion, and need for post-operative blood transfusions. Unfortunately, due to the substantial variability of methodology (not all PRP preparations are the same) in the available studies as well as the variability in outcomes reporting, direct comparison between different studies is not feasible. Here, we discuss the basic science elements of PRP relevant to arthroplasty, the variability of PRP solutions, the specific applications of PRP in arthroplasty, and the latest clinical outcomes analyses of patients undergoing PRP therapy in conjunction with shoulder arthroplasty

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

We investigated the effect of Platelet Rich Plasma (PRP) in tendon healing. The aim was to assess the effect of an application of PRP on angiogenesis and immunohistochemical expression of TGF-b1 and IGF-I during tendon healing. We used a patellar tendon defect model after resecting its central portion. 48 skeletally mature New Zealand White rabbits were divided into the respective group and each group they were randomised into controls and PRP treated cases. The rabbits were sacrificed at weekly intevals and histological and immunohistological assessments were performed. The results showed a faster healing rate, increased vascularity, and higher expression of the growth factors in the PRP group. We conclude that the mixture of growth factors present in PRP gel improved the rate and quality of tendon healing

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

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

Introduction. Platelet Rich Plasma (PRP) is widely used in clinical praxis. Especially the effects in musculoskeletal repair studies are diverse and an augmentation of healing processes stays questionable. However, diverse cell culture studies reported promising results, which seem not be transferable into the clinical situation. We therefore performed a cell culture study which better reflects the clinical situation: the autologous stimulation of human tendon cells with PRP. Materials and Methods. Human tenocyte-like cells (hTLCs) from 24 donors (12 male/female) with supraspinatus tendon tears were isolated and characterized. The donors were grouped into 4 groups according to their age (</> 65 years) and sex. During follow up, approximately 2.5 years after initial surgery, the patients donated blood for PRP preparation (Ethic vote and written informed consent). Growth factors and platelets were quantified and the effect of autologous stimulation of the hTLCs was measured by analysis of cell proliferation, Collagen I synthesis and expression of Collagen I, III and Osteocalcin. Results. The platelet concentration for the 4 groups was between 3.6–4.5 × 10. 5. platelets/µl (reference level: 1.5–3×10. 5. platelets/µl blood). PRP contained high amounts of IGF-1, lower amounts of TGF-β1 and PDGF-AB. PDGF-AB concentration significantly correlated with platelet concentration and the TGF-β1 concentration. The amounts of BMP-7 and −12 were underneath the detection limits of the assays. Cell proliferation was positively affected by PRP exposure when compared to controls (2% FCS and 10% FCS) (p<0.05). However, the expression and synthesis of Collagen I was significantly reduced compared to controls. Collagen III expression was partly increased, while Osteocalcin expression was not affected. Discussion. PRP is a source of growth factors such as IGF-1, TGF-β and PDGF-AB. It has a high potential to stimulate cell proliferation, which might have a positive effect in clinical applications. However, the decreased expression and synthesis of Collagen I, the most important Collagen in the tendon, might explain the, to date, less satisfactory clinical results. PRPs might have their potential in chronic situation with pain reducing function rather than in acute healing situations. Further studies are necessary to better understand these mechanisms

Background. Processing of allografts, which are used to fill bone defects in orthopaedic surgery, includes chemical cleaning as well as gamma irradiation to reduce the risk of infection. Viable bone cells are destroyed and denaturing proteins present in the graft the osteoconductive and osteoinductive characteristics of allografts are altered. The aim of the study was to investigate the mechanical differences of chemical cleaned allografts by adding blood, clotted blood, platelet concentrate and platelet gel using a uniaxial compression test. Methods. The allografts were chemically cleaned, dried and standardized according to their grain size distribution. In group BL 4 ml blood, in CB 4 ml blood and 480 μl of 1 mol calcium chloride to achieve clotting, in PC 4 ml of concentrated platelet gel, in PG 4 ml of concentrated platelets and 666 μl of 1 mol calcium chloride were added. Uniaxial compression test was carried out for the four groups before and after compating the allografts. Results. No statistically significant decrease of the initial density was observed after compaction for BL and PC. In CB a statistical significant decrease of the initial density by 10% was observed, while PG decreased its initial density after compaction by 13%. Considering the density at the yield limit before and after compaction BL showed a statistically significant decrease of 13% and PG of 14%. In CB and PC no statistically significant decrease of the density at the yield limit could be observed. All groups showed a statistical significant difference when comparing the yield limit before and after compaction. BL and PC showed a ∼35% higher yield limit after compaction, while in the groups with the activation liquid CB and PG the yield limit increased by 15% for CB and 20% for PG. No statistically significant difference between groups was found for the density at the yield limit before compaction (p=0.157), for the initial density (p=0.523), the density at the yield limit (p=0.681) and the yield limit itself (p=0.423) after compaction. A statistically significant difference between the groups under investigation was found for the initial density before compaction (p=0.041) and for the yield limit before compaction (p=0.041). BL had a statistically significant lower initial density than PG (p=0.048). All other pairwise comparisons between groups did not reach statistically significance for the initial density before compaction. Conclusion. Adding blood, PRP or PC in allografts has shown in different studies to enhance bone ingrowth. The authors recommend to chemical clean allografts for large defects, optimize their grain size distribution and add platelet concentrate or platelet rich plasma for enhancing as well primary stability as well bone ingrowth. The recommended processing procedure has to be tested in an in-vivo study

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. Platelets play a central role in haemostasis and wound healing. We have used autologous Platelet Rich Plasma (PRP) to stimulate healing in a variety of cases. We would like to present our early experience with this technique. Method. PRP is produced by centrifuging a sample of the patient’s blood. The volume of PRP produced is about 10% of the original volume. Thrombin, derived from the patient’s plasma, is mixed with the PRP to produce a platelet gel. This gel is semi-solid and makes the PRP more manageable intra-operatively. It can be used on its own, mixed with bone graft or de-mineralised bone matrix (DBM.). Results. We have used platelet gel in 14 cases for a variety of clinical conditions. 57% were males and the mean age was 44.1 (range: 7–77.) Cases included 3 elective joint fusions, 7 non unions, 2 case of chronic osteomyelitis, 1 acute fracture and 1 pathological fracture. The gel was mixed with autologous bone graft in 10 cases, DBM in 1 case and used on its own in 3 cases. The number of cases is too small to make any comment on the rate of bone union. Some practical issues have arisen during the use of platelet gel. Discussion. Is it better to give a large number of growth factors at slightly above background levels or a single growth factor millions of times above background level? This paper doesn’t answer that question but because wound and bone healing relies upon a cascade of growth factors, it is attractive to be able to provide many of these factors. Further studies are required to answer this fundamental question

Introduction. Ostochondral lesion of the knee is a common cause of chronic knee pain. Arthroscopic treatment with subcondral microfracture is a widespread technique leading to noticeable improvement of knee function and pain. To improve the effectiveness of this treatment options, we thought to add intra (PRF) or post-operative (PRP) growth factors. Platelet rich plasma (PRP) is obtained by centrifugation of the blood to produce a plasma with high concentration of platelets and growth factors. This latter represents a promising method to manage degenerative cartilage lesion and can be used postoperatively to improve clinical results of patients treated arthroscopically. Platelet Rich Fibrin (PRF) has been presented as a second-generation platelet concentrate, and it is used intraoperatively to cover the microfracuteres’ holes. No literature was found about using of PRF intraoperative in association with arthroscopic microfracture technique. The aim of this study is to compare clinical outcomes of the treatment of knee osteochondral lesion using arthroscopic microfracture technique alone or in association with PRF Intraoperative application using “Vivostat” system or with PRP “ReGen Lab” postoperative injection. Patients & Methods. 90 patients with clinical and radiographic evidence of osteochondral lesion of the medial or lateral compartment of the knee were enrolled. All patients received arthroscopic debridement and Microfractures and were randomised into 3 groups: 30 patients received microfractures and intraoperative PRF “Vivostat” injection(Group A), 30 patients received microfracture and 3 intra-articular injections of 5.5 mL PRP “Regen”(Group B), 30 patients received microfracture only. IKDC, KOOS and VAS score were administered to all patients before starting the treatment, at 1, 6 and 12 months from the end of the management. Results. Patients who received microfracture and PRF intraoperative application provided the best outcomes, showing a significant higher clinical scores (P<0.001) compared to the other two groups. Patients underwent PRP postoperative administration reported significant higher score than those undergoing arthroscopic microfracture alone (P<0.005), but lesser than Intraoperative PRF group at 6 months and 1 year follow up. Discussion/Conclusion. Treatment of osteochondral lesions of the knee using microfracture technique significantly improved functional and pain scores from the pre- to postoperatively time in the overall cohort. Intraoperative application of PRF shows significantly better outcome than postoperative PRP injections. However, additional treatment with intra-articular PRP injection as an adjunct to microfracture technique may offer better clinical outcomes over microfracture technique alone

For degenerative osteoarthritis of the knees, a variety of non-surgical management options have been tried from time to time. Medical management, chondroprotective agents, disease modifying drugs, viscosupplimentation etc. to name a few. Arthroscopic knee lavage with saline also has shown good results, with the effect of cleaning the debries from the joint. Growth Factors Rich Plasma (GFRP) or Platelet Rich Plasma (PRP) is an emerging treatment therapy called “ Orthobiologics”. Alfa granules in platelets contain numerous growth factors which enhance tissue recovery dramatically by catalyzing the body's natural healing response. PRP also attracts Mesenchymal Stem Cells, which differentiate into variety of cell types during tissue repair processes & induce the production of new collagen by the fibroblasts, osteoblasts and chondrocytes as per the need of the parent tissue. Knee lavage is done under local anesthesia using single antero-lateral portal. Four liters of saline is used to lavage the knee and at the end of procedure 80 mg. methyl prednisolone is injected. For GFRP injection, 100 cc of patient's blood is double centrifuged in the refrigerated blood component separator centrifuge in the blood bank giving about 15 cc of buffy layer having GFRP. Since Feb. 2010, more than 1000 knees of different grades of osteoarthritis have been injected with GFRP and the results compared with other different treatment options. Results of few different combination therapies are presented in this study. 1. Knee Lavage Vs Autologous GFRP Injection (100+100 cases) 2. Knee Lavage + Autologous GFRP Injection in 1 knee Vs GFRP Injection only in other knee (200+200 Knees) 3. Visco-supplimentation Vs Autologous GFRP Injection. (10+10cases). Results were analyzed up to 1 year as per VAS scale. Knee Lavage clears the joint of the microscopic and macroscopic debris of the cartilage and synovium which are causing chemical and mechanical irritation resulting in the inflammatory cascade. GFRP injection tries to repair the cartilage by the efficacy of the Growth factors contained therein. It has been observed that Knee Lavage and GFRP Injection have almost similar efficacy at 1 year, though knee lavage starts showing its effects early. GFRP therapy has shown better results compared to visco supplimentation at 1 year. Combination of knee lavage with GFRP injection showed much better results than GFRP injection alone and the results are inversely related to the grade of the osteoarthritis. Viscosupplimentation has very short lived efficacy. It's concluded that Knee Lavage followed by GFRP injection gives the best long term results and this pilot project initiated, hopefully will go a long way in future to change the course of the management for osteoarthritis knees at a minimal cost and may obviate the need for Knee arthroplasty if started in early stages of Osteoartrhritis

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

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. Introduction. The management of bone defects continues to present challenges. Upon activation, platelets secrete an array of growth factors that contribute to bone regeneration. Therefore, combining platelet rich plasma (PRP) with bone graft substitutes has the potential to reduce or replace the reliance on autograft. The simple, autologous nature of PRP has encouraged its use. However, this enthusiasm has failed to consistently translate to clinical expediency. Lack of standardisation and improper use may contribute to the conflicting outcomes reported within both pre-clinical and clinical investigations. This study investigates the potential of PRP for bone augmentation in an older age sheep model. Specifically, PRP dose is controlled to provide clearer indications for its clinical use. Methods. Eighty 11mm diameter defects of 20mm in depth were created in the cancellous bone within the epiphyseal region of the medial proximal tibia and distal femur of twenty five-year-old sheep. The defects were treated with three doses of an autologous thrombin activated PRP combined with a biphasic calcium phosphate (BCP). Activated platelet poor plasma (PPP) and the BCP alone provided reference groups, while the autograft and empty defects served as controls. All animals were sacrificed at four weeks post-operatively for radiographic assessment, micro-computed tomography quantification, histological assessment, histomorphometric quantification of new bone area and bone ingrowth, and weekly fluorochrome bone label quantification. TGF-β1 concentrations were quantified using enzyme-linked immunosorbent assays. Results. The PRP had a 2.9-fold (0.4) increase in platelet concentration, a 0.57-fold (0.09) decrease in leukocytes, and a 0.65-fold (0.11) decrease in fibrinogen. After activation, the PRP had an 8.9-fold (1.5) increase in TGF-β1 serum concentration above baseline. Eleven (11) mm diameter cancellous bone defects in the hind legs of five-year-old sheep do not spontaneously heal within four weeks. PRP dose had a significant effect on the radiographic grade. The highest dose of PRP treatment had a significantly greater micro-CT BV/TV over the BCP alone (PRP: 30.6±1.8%; BCP: 24.5±0.1%). All doses of PRP treatment were significantly greater than the BCP alone for both the histomorphometric new bone area (PRP: 14.5±1.3%; BCP: 9.7±1.5%) and bone ingrowth depth (PRP: 2288±210µm; BCP:1151±268µm). From week two onwards, PRP had a significant effect on the weekly bone ingrowth over BCP, however, autograft had the greatest amount of fluorescently labelled bone within the first three weeks. PRP has a significant effect on the shape and density of osteoblasts within the central region of the defect compared to the BCP alone, however, was not significantly different to autograft. TGF-β1 appeared a better predictor of healing outcomes than platelet concentration, however both had relatively weak correlations (r<.324). Conclusion. PRP induces new bone formation with a dose dependant response at four weeks when used with a biphasic calcium phosphate in older age sheep

Autologous platelet rich plasma (PRP) has an established history of clinical use in dental and orthopaedic procedures. However, there is little scientific data demonstrating a mode of action and conflicting clinical data to support its use. The aim of this study was to determine the cellular and metabolic pathways by which PRP modulates the osteogenic response. PRP is a concentrate of platelets in a small volume of plasma derived from whole blood. Platelets contain pre-packaged growth factors in & #61537;-granules that are released during clotting at the trauma site and are an essential requirement for the hard (bone) and soft tissue healing process. S& N’s Caption ™ device, a standalone disposable device that prepares autologous PRP in 15minutes, was used to prepare human PRP. We determined a platelet concentration factor of 3.4& #61617;1.2 fold and significant increases in the concentration of platelet derived growth factor–AB (PDGF-AB), transforming growth factor-& #61538; (TGF-& #61538;) and vascular endothelial growth factor (VEGF). A 5.9 fold increase in VEGF, 4 fold increase in TGF-& #61538; and 1.5 fold increase in PDGF-AB indicate that PRP has the potential to enhance bone repair as each of these growth factors individually and synergistically affect multiple cell responses essential for tissue repair. An in vitro study was then undertaken to investigate the effect of human PRP compared to human serum on the proliferation and differentiation of human primary osteoblasts (hOBs) and human mesenchymal stem cells (hMSCs). A significant proliferative effect of PRP compared to serum was observed in both cell types. In hMSCs, PRP treatment significantly increased proliferation after 24 hours as determined by Pico green analysis. However, in osteoblasts a proliferative effect of PRP over and above that of serum was not observed until 72 hours. These data indicate that PRP may have specific differing stimulatory effects on each cell type. Quantitative RT-PCR analysis also determined that PRP significantly increased the expression of BMP 2 over and above that of serum in human osteoblasts at both 6 and 12 hour time points. Furthermore, in hMSCs, PRP increased both BMP-2 and alkaline phosphatase gene expression at early time points suggesting the commitment of these cells to the osteoblastic lineage. This hypothesis was consistent with alkaline phosphatase protein expression which was significantly increased at 72hrs in hMSCs and was further confirmed by increased alizarin red staining, indicative of calcium deposition, in long term cultures of hMCSs treated with PRP. In summary, these data demonstrate that PRP initiates proliferation in hMSCs and osteoblasts, enhances BMP-2 mRNA expression and induces osteoblast differentiation and maturation in human MSC cultures. Together these data demonstrate a positive effect of PRP on osteogenesis and highlight the potential for Caption™ derived PRP to enhance bone repair

Arthrodesis of the spine is the preferred surgical treatment for a number of pathological disorders. This process is dependent on three primary components: osteogenic cells with osteoblastic potential, osteoinductive growth factors and an osteoconductive scaffold that facilitates bone formation and vascular ingrowth. Several systemic and local factors are known to affect the rate of spinal fusion. Autogenous bone graft remains the gold standard graft material for spinal fusion. It is the only graft material that supplies the three primary components necessary for a solid fusion. Unfortunately autogenous bone is only available in limited quantities and the procurement of autograft is associated with significant donor site morbidity. A number of different bone graft materials have been developed as alternatives to autograft. These materials may be classified into two major groups, bone graft extenders used to augment autograft, or bone graft substitutes. Several different bone graft materials have been developed including allograft, osteoconductive matrices, demineralised bone matrices, bone marrow aspiration, autologous platelet concentration, growth factors and gene therapy. Allograft is currently the most widely used substitute for autogenous bone. Because any osteogenic cells are eradicated during the tissue processes, allograft is primary osteoinductive with minimal osteoinductive potential. Processing may affects the structural and biological characteristics of a graft. The incorporation of allograft occurs by a process similar to that observed with autograft but more slowly and is less complete. Osteoconductive scaffolds do not contain any osteogenic cells or osteoinductive factors and are used as a composite graft as a carrier for either osteogenic cells or osteoinductive growth factors. They are biocompatible and do not illicit a response. There is also no inherent risk of infection and availability is unlimited. These materials are brittle with poor mechanical properties and need to be protected from excessive biomechanical forces until fully incorporated. A number of osteoconductive scaffolds have been developed including ceramics, calcium sulfate, mineralized collagen, bioactive glasses, and porous metals. Dematerialized bone matrices (DMPs) are osteoinductive with variable osteoconductive properties. DMPs consist of Type I collagen and non-collagenous proteins including multiple signaling proteins. The osteoinductive activity of DMPs is due to a small fraction of bone morphogenic proteins. There is significant variability in the osteoinductive potentials and clinical efficacy of DBMs. DBMs are most effective when combined with autograft or bone marrow aspirate. Bone marrow aspiration provides osteogenetic cells and osteoinductive growth factors but must be combined with an osteoconductive carrier to form a composite graft. It is associated with minimal morbidity compared to the use of autograft and is easily obtained. Unfractionated bone marrow contains only moderate osteogenic potential. Selective retention technology can increase the number of osteogenic cells then combined with an osteoconductive carrier such as a collagen sponge or DBM. Activated platelets release multiple factors that may enhance bone formation by promoting chemotaxis, cellular proliferation and differentiation of stem cells. Platelets do not release BMPs so this autologous platelet concentrate is not inductive. Concentrated platelet rich plasma gel is combined with an osteoconductive scaffold or osteogenic cells to form a composite graft for implantation. The capacity for fusion by this technique may be inferior to autologous graft. Bone morphogenetic proteins are low molecular weight proteins related to the transforming growth factor beta superfamily. They bind receptors on the surface of osteoprogenitor stem cells and activate intracellular signal transduction cascades resulting in the osteoblastic differentiation of pluripotential stem cells. Recombinant BMPs are typically combined with an osteoconductive carrier to form a composite graft. Recombinant BMPs have been used successfully in spinal fusions and may be superior to autograft. Gene therapy involves the transfer of specific DNA sequence into target cells that express the protein of interest. Gene therapy may provide a more potent osteoinductive signal than recombinant growth factors because the sustained local release of osteogentic proteins may be more physiologic than the administration of a single large dose of recombinant factors. There are potential safety concerns and economic issues. Autogenous bone remains the gold standard of graft material; however composite grafts consisting of multiple materials may prove to be efficacious for stimulating a spinal fusion

Aims

Despite the increase in the surgical repair of proximal hamstring tears, there exists a lack of consensus in the optimal timing for surgery. There is also disagreement on how partial tears managed surgically compare with complete tears repaired surgically. This study aims to compare the mid-term functional outcomes in, and operating time required for, complete and partial proximal hamstring avulsions, that are repaired both acutely and chronically.

Objectives

Mesenchymal stem cells have the ability to differentiate into various cell types, and thus have emerged as promising alternatives to chondrocytes in cell-based cartilage repair methods. The aim of this experimental study was to investigate the effect of bone marrow derived mesenchymal stem cells combined with platelet rich fibrin on osteochondral defect repair and articular cartilage regeneration in a canine model.

Aims

Local antibiotics are used in the surgical management of foot infection in diabetic patients. This systematic review analyzes the available evidence of the use of local antibiotic delivery systems as an adjunct to surgery.

Aims

While medial unicompartmental knee arthroplasty (UKA) is indicated for patients with full-thickness cartilage loss, it is occasionally used to treat those with partial-thickness loss. The aim of this study was to investigate the five-year outcomes in a consecutive series of UKAs used in patients with partial thickness cartilage loss in the medial compartment of the knee.

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).

We report the outcome of 84 nonunions involving long bones which were treated with rhBMP-7, in 84 patients (60 men: 24 women) with a mean age 46 years (18 to 81) between 2003 and 2011. The patients had undergone a mean of three previous operations (one to 11) for nonunion which had been present for a mean of 17 months (4 months to 20 years). The nonunions involved the lower limb in 71 patients and the remainder involved the upper limb. A total of 30 nonunions were septic. Treatment was considered successful when the nonunion healed without additional procedures. The relationship between successful union and the time to union was investigated and various factors including age and gender, the nature of the nonunion (location, size, type, chronicity, previous procedures, infection, the condition of the soft tissues) and type of index procedure (revision of fixation, type of graft, amount of rhBMP-7) were analysed. The improvement of the patients’ quality of life was estimated using the Short Form (SF) 12 score.

A total of 68 nonunions (80.9%) healed with no need for further procedures at a mean of 5.4 months (3 to 10) post-operatively. Multivariate logistic regression analysis of the factors affecting union suggested that only infection significantly affected the rate of union (p = 0.004).Time to union was only affected by the number of previous failed procedures (p = 0.006). An improvement of 79% and 32.2% in SF-12 physical and mental score, respectively, was noted within the first post-operative year.

Rh-BMP-7 combined with bone grafts, enabled healing of the nonunion and improved quality of life in about 80% of patients. Aseptic nonunions were much more likely to unite than septic ones. The number of previous failed operations significantly delayed the time to union.

Cite this article: Bone Joint J 2015;97-B:997–1003.

Objectives

In order to ensure safety of the cell-based therapy for bone regeneration, we examined in vivo biodistribution of locally or systemically transplanted osteoblast-like cells generated from bone marrow (BM) derived mononuclear cells.