Mikel Sánchez

Comparison of Surgically Repaired Achilles Tendon Tears Using Platelet-Rich Fibrin Matrices

Background Platelet-rich fibrin matrices release a natural mixture of growth factors that play central roles in the complex processes of tendon healing. Hypothesis Application of autologous platelet-rich matrices during Achilles tendon surgery may promote healing and functional recovery. Study Design Case-control study and descriptive laboratory study; Level of evidence, 3. Methods Twelve athletes underwent open suture repair after complete Achilles tendon tear. Open suture repair in conjunction with a preparation rich in growth factors (PRGF) was performed in 6 athletes and retrospectively compared with a matched group that followed conventional surgical procedure. The outcomes were evaluated on the basis of range of motion, functional recovery, and complications. Achilles tendons were examined by ultrasound at 50 ± 11 months in retrospective controls and 32 ± 10 months in the PRGF group. In the laboratory portion of the study, PRGF treatment was characterized by the number of platelets and concentration of insulin (IGF-I), transformed (TGF-β1), platelet-derived (PDGF-AB), vascular endothelial (VEGF), hepatocyte (HGF), and epidermal (EGF) growth factors in patients affected by musculoskeletal traumatic injuries. Results Athletes receiving PRGF recovered their range of motion earlier (7 ± 2 weeks vs 11 ± 3 weeks, P = .025), showed no wound complication, and took less time to take up gentle running (11 ± 1 weeks vs 18 ± 3 weeks, P = .042) and to resume training activities (14 ± 0.8 weeks vs 21 ± 3 weeks, P = .004). The cross-sectional area of the PRGF-treated tendons increased less (t = 3.44, P = .009). TGF-β1 (74.99 ± 32.84 ng/mL), PDGF-AB (35.62 ± 14.57 ng/mL), VEGF (383.9 ± 374.9 pg/mL), EGF (481.5 ± 187.5 pg/mL), and HGF (593.87 ± 155.76 pg/mL) significantly correlated with the number of platelets (677 ± 217 platelets/μL, P < .05). Conclusion The operative management of tendons combined with the application of autologous PRGF may present new possibilities for enhanced healing and functional recovery. This needs to be evaluated in a randomized clinical trial.

Platelet-rich therapies in the treatment of orthopaedic sport injuries.

Biomedical sciences have made major advances in understanding how tissues repair, and the signalling mechanisms required to achieve this goal are progressively being dissected. Advances in the understanding of tissue repair mechanisms and the pivotal role of growth factors have stimulated the use of platelet-rich therapies by orthopaedic surgeons and sports physicians, mainly with the aim of stimulating and enhancing tissue healing. Autologous activated platelets retained in fibrin matrices are used as a source of molecular signals that control cell fate, including cell growth, cell differentiation and the synthesis of diverse functional proteins. Thus far, platelet-rich technologies have spawned additional ambitious endeavours, including surgical and nonsurgical treatments in sports orthopaedics. Reconstruction of anterior cruciate ligament and tendon surgery and treatment of joint injuries, tendinopathy or muscle tears are but a few examples of the potential applications of this technology in the field of orthopaedic sports medicine. In the present article, some of the most important therapeutic applications using these approaches–especially preparation rich in growth factor (PRGF) technology–are presented, as are some of the limitations, anti-doping concerns and future challenges in the field. In view of a general state of confusion, the concept of platelet-rich plasma needs rigorous definition associated with well characterized products and re-administration procedures. There is evidence that reconstruction of anterior cruciate ligament and tendon surgery combined with PRGF enhances healing and functional recovery; clinical evidence is also appearing in the literature regarding treatment of tendinopathies and osteoarthritis. Currently, the challenge lies in conducting randomized, controlled clinical trials to determine the essential qualities of these technologies. If anti-doping agencies clarify their regulatory guidelines, robust studies in athletes are expected to emerge. Although much research work lies ahead, the current knowledge points to a future in which platelet-rich therapies will continue improving existing conventional approaches to treatment of sports injuries.

Plasma Rich in Growth Factors to Treat an Articular Cartilage Avulsion: A Case Report

INTRODUCTION The application of an autologous plasma rich in growth factors is beneficial in restoring connective tissues, as shown by clinical evidence in oral surgery and more recently in arthroscopic anterior cruciate ligament reconstruction and two cases of ruptured Achilles tendon in professional athletes. This is attributed to the slow delivery of growth factors from harvested platelets that have been activated by endogenous thrombin promoted by the addition of calcium chloride. PURPOSE This case report describes a new application of this therapy in the arthroscopic treatment of a large, nontraumatic avulsion of articular cartilage in the knee of an adolescent soccer player. METHODS After arthroscopic reattachment of the large (>2 cm) loose chondral body in its crater in the medial femoral condyle, autologous plasma rich in growth factors was injected into the area between the crater and the fixed fragment. RESULTS AND CONCLUSION Despite the extremely poor prognosis of the case, complete articular cartilage healing was considerably accelerated, and the functional outcome was excellent, allowing a rapid resumption of symptom-free athletic activity. This technique opens new perspectives for human tissue regeneration.

A randomized clinical trial evaluating plasma rich in growth factors (PRGF-Endoret) versus hyaluronic acid in the short-term treatment of symptomatic knee osteoarthritis.

PURPOSE This multicenter, double-blind clinical trial evaluated and compared the efficacy and safety of PRGF-Endoret (BTI Biotechnology Institute, Vitoria-Gasteiz, Spain), an autologous biological therapy for regenerative purposes, versus hyaluronic acid (HA) as a short-term treatment for knee pain from osteoarthritis. METHODS We randomly assigned 176 patients with symptomatic knee osteoarthritis to receive infiltrations with PRGF-Endoret or with HA (3 injections on a weekly basis). The primary outcome measure was a 50% decrease in knee pain from baseline to week 24. As secondary outcomes, we also assessed pain, stiffness, and physical function using the Western Ontario and McMaster Universities Osteoarthritis Index; the rate of response using the criteria of the Outcome Measures for Rheumatology Committee and Osteoarthritis Research Society International Standing Committee for Clinical Trials Response Criteria Initiative (OMERACT-OARSI); and safety. RESULTS The mean age of the patients was 59.8 years, and 52% were women. Compared with the rate of response to HA, the rate of response to PRGF-Endoret was 14.1 percentage points higher (95% confidence interval, 0.5 to 27.6; P = .044). Regarding the secondary outcome measures, the rate of response to PRGF-Endoret was higher in all cases, although no significant differences were reached. Adverse events were mild and evenly distributed between the groups. CONCLUSIONS Plasma rich in growth factors showed superior short-term results when compared with HA in a randomized controlled trial, with a comparable safety profile, in alleviating symptoms of mild to moderate osteoarthritis of the knee. LEVEL OF EVIDENCE Level I, randomized controlled multicenter trial.

Fibroblastic response to treatment with different preparations rich in growth factors

Objectives:  Preparations rich in growth factors (PRGF) release them plus bioactive proteins at localized sites, with the aim of triggering healing and regenerative processes. The prevailing paradigm suggests that their influence on proliferation, angiogenesis and the extracellular matrix synthesis is minimal. However, variations in their composition and impact on different cell phenotypes have not been examined.

Ligamentization of Tendon Grafts Treated With an Endogenous Preparation Rich in Growth Factors: Gross Morphology and Histology

PURPOSE To investigate whether the application of a particular platelet-rich plasma preparation rich in growth factors (PRGF) during anterior cruciate ligament (ACL) surgery gives a potential advantage for better tendon graft ligamentization. METHODS This study included 37 volunteers who underwent either conventional (control group, n = 15) or PRGF-assisted (n = 22) ACL reconstruction with an autogenous hamstring and required second-look arthroscopy to remove hardware or loose bodies, treat meniscal tears or plica syndrome, or resect cyclops lesions at 6 to 24 months after ACL surgery. The gross morphologies of the grafts were evaluated on second-look arthroscopy by use of the full arthroscopic score (0 to 4 points) to evaluate graft thickness and apparent tension (0 to 2 points) plus synovial coverage (0 to 2 points). At the same time, biopsy specimens were harvested uniformly from the grafted tendons. In these specimens the histologic transformation of the tendon graft to ACL-like tissue was evaluated by use of the Ligament Tissue Maturity Index, and a score to assess the progression of new connective tissue enveloping the graft was created by use of 3 criteria previously used to characterize changes during ligament healing: cellularity, vascularity, and collagen properties. RESULTS The overall arthroscopic evaluation of PRGF-treated grafts showed an excellent rating in 57.1% of the knees (score of 4) and a fair rating in 42.9% (score of 2 or 3). In contrast, evaluation of untreated grafts showed an excellent rating in 33.3% of the knees, a fair rating in 46.7%, and a poor rating in 20% (score of 0 or 1). Overall, arthroscopic evaluations were not statistically different between PRGF and control groups (P = .051). PRGF treatment influenced the histologic characteristics of the tendon graft, resulting in tissue that was more mature than in controls (P = .024). Histologically evident newly formed connective tissue enveloping the graft was present in 77.3% of PRGF-treated grafts and 40% of controls. The appearance of the connective tissue envelope changed with increasing time from surgery. On the basis of the histologic findings, we suggest that the remodeling of PRGF-treated grafts involves the formation of synovial-like tissue enveloping the graft. This tissue is eventually integrated in the remodeled tendon graft, conferring a similar appearance to the normal ACL. CONCLUSIONS The use of PRGF influenced the histologic characteristics of tendon grafts, resulting in more remodeling compared with untreated grafts. We have shown temporal histologic changes during the 6- to 24-month postoperative period of graft maturation, with newly formed connective tissue enveloping most grafts treated with PRGF. LEVEL OF EVIDENCE Level III, case-control study.

Potential of endogenous regenerative technology for in situ regenerative medicine

Endogenous regenerative technology (Endoret) involves the use of patients own biologically active proteins, growth factors and biomaterial scaffolds for therapeutic purposes. This technology provides a new approach for the stimulation and acceleration of tissue healing and bone regeneration. The versatility and biocompatibility of using patient-derived fibrin scaffold as an autologous, biocompatible and biodegradable drug delivery system open the door to a personalized medicine that is currently being used in numerous medical and scientific fields including dentistry, oral implantology, orthopaedics, ulcer treatment, sports medicine and tissue engineering among others. This review discusses the state of the art and new directions in the use of endogenous technology in the repair and regeneration of injured tissues by means of a controlled and local protein and growth factor delivery. The next generations of engineering strategies together with some of the most interesting therapeutic applications are discussed together with the future challenges in the field.

Ultrasound-guided platelet-rich plasma injections for the treatment of osteoarthritis of the hip

OBJECTIVE To assess the safety and symptomatic changes of IA injections of platelet-rich plasma (PRP) in patients with OA of the hip. METHODS Forty patients affected by monolateral severe hip OA were included in the study. Each joint received three IA injections of PRP, which were administered once a week. The primary end point was meaningful pain relief, which was described as a reduction in pain intensity of at least 30% from baseline levels as evaluated by the WOMAC subscale at 6-months post-treatment. The visual analogue scale (VAS) and Harris hip score subscale for pain were used to verify the results. Secondary end points included changes in the level of disability of at least 30% and the percentage of positive responders, i.e. the number of patients that achieved a >30% reduction in pain and disability. RESULTS Statistically significant reductions in VAS, WOMAC and Harris hip subscores for pain and function were reported at 7 weeks and 6 months (P < 0.05). Twenty-three (57.5%) patients reported a clinically relevant reduction of pain (45%, range 30-71%) as assessed by the WOMAC subscale. Sixteen (40%) of these patients were classified as excellent responders who showed an early pain reduction at 6-7 weeks, which was sustained at 6 months, and a parallel reduction of disability. Side effects were negligible and were limited to a sensation of heaviness in the injection site. CONCLUSIONS This preliminary non-controlled prospective study supported the safety, tolerability and efficacy of PRP injections for pain relief and improved function in a limited number of patients with OA of the hip.

Tendon healing and platelet-rich plasma therapies

Importance of the field: The therapeutic use of platelet-rich plasma (PRP) is an autologous biotechnology that relies on the local delivery of a wide range of growth factors and cytokines with the aim of enhancing tissue healing. Understanding both tendon healing and PRP therapies is an area of research that is critically important in developing optimal formulations and protocols to achieve the intended therapeutic effects. Areas covered in this review: We summarise recent information on the mechanisms inherent to the earliest response to tendon injury. We then describe the positive effect of PRP therapies on tendon healing. Research on tendinopathy has produced several biological hypotheses based on histopathological, biochemical and clinical findings showing that cell apoptosis, angiofibroblastic features or abnormal biochemical adaptations underlie the condition. What the reader will gain: The article provides insights into early healing mechanisms and the influence of PRP therapies on inflammation, cell migration, angiogenesis and the proliferation and synthesis of extracellular matrix. The knowledge gained helps to better understand and optimize tendon therapies. Take home message: The use of endogenous therapies has a positive effect on experimental tendon healing. However, several obstacles need to be addressed to optimise medical practice in this field.

Reciprocal Actions of Platelet-secreted Tgf-β1 on the Production of Vegf and Hgf by Human Tendon Cells

Background: Autologous platelet-rich matrices can be an aid in surgery by promoting and accelerating tissue healing because of the release of growth factors including transforming growth factor (TGF)-&bgr;1 and platelet-derived growth factor (PDGF) from platelet &agr;-granules. Methods: PDGF and TGF-&bgr;1 were quantified in supernatants collected from platelet-rich matrices prepared in vitro (n = 45 donors) and they correlated with the number of platelets and showed a constant ratio (p < 0.05). Tendon cells in culture were exposed to the supernatants (n = 4 donors) from either platelet-rich or platelet-poor matrices, differing in their content of platelet-secreted molecules. These treatments were modified by either neutralizing or adding PDGF or TGF-&bgr;1. Effects were compared in terms of proliferation, procollagen I, vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF) production. Results: PDGF was a partial contributor to cell proliferation, whereas exogenous TGF-&bgr;1 acted as a negative modulator (p < 0.05). The production of type I collagen was similar regardless of differences in the concentration of TGF-&bgr;1. Moreover, addition of exogenous TGF-&bgr;1 promoted a significant increase in collagen synthesis only in the absence of other platelet-released substances (p < 0.05). Exogenous TGF-&bgr;1 increased the synthesis of VEGF and simultaneously abolished the production of HGF. Furthermore, antibody-mediated neutralization of TGF-&bgr;1 induced a decrease in VEGF synthesis and concomitantly a substantial production of HGF (p < 0.05). Conclusion: The balance between TGF-&bgr;1 and the pools of platelet-secreted molecules may have important therapeutic implications in the control of angiogenesis and fibrosis.