Clinical Evaluation of Safety and Efficacy of a Central Current Good Manufacturing Practices Laboratory Produced Autologous Adipose-Derived Stromal Vascular Fraction Cell Therapy Product for the Treatment of Knee Osteoarthritis.

Knee osteoarthritis (KOA) is a prevalent condition characterized by the progressive deterioration of the entire joint and has emerged as a prominent contributor to disability on a global scale. The nature of the disease and its impact on joint function significantly limit mobility and daily activities, highlighting its substantial influence on patients' overall well-being. Stromal vascular fraction (SVF) is a heterogenous, autologous cell product, containing mesenchymal stem cells, derived from the patient's subcutaneous adipose tissue with demonstrated safety and efficacy in the treatment of KOA patients. We conducted a single-arm, open-label, multisite, FDA approved clinical study in Kellgren-Lawrence severity grade 2-4 KOA patients. The cellular product was manufactured from patient-specific lipoaspirate in a centrally located FDA-compliant manufacturing facility. Twenty-nine subjects were treated with a quality tested single intra-articular injection of GMP manufactured SVF. Adverse events, laboratory values, vital signs, and physical examination findings were monitored during the study period. Robust tolerability, without any substantial safety issues, was demonstrated. Knee pain and function, assessed through the Knee Injury and Osteoarthritis Outcome Score (KOOS), demonstrated notable improvements. These positive benefits persisted for up to 12 months, and the majority of participants expressed satisfaction. SVF from each patient was stored in a liquid nitrogen freezer for future clinical treatments. Unique to this study of autologous cells is the shipment of lipoaspirate from the clinic to a central FDA-compliant manufacturing facility for cleanroom-controlled manufacturing. The cell product characterization data demonstrate that this method produces an equivalent product in terms of cell count and viability with the added benefit of further quality assurance testing, including sterility, endotoxin, and flow cytometry, before patient administration. Clinical Trial Registration Number: NCT04043819.

Use of extracorporeal shockwave therapies for athletes and physically active individuals: a systematic review.

OBJECTIVE: To determine the efficacy of extracorporeal shockwave therapy (ESWT) and investigate outcomes following the use of ESWT for athletes and physically active individuals. DESIGN: Systematic review. DATA SOURCES: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and searched four databases: PubMed (NLM), Embase (Elsevier), CINAHL Complete (EBSCO) and Web of Science (Clarivate). ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Included studies were randomised controlled trials, cohort and case-control studies, cases series and reports that evaluated outcomes following ESWT for athletes, physically active individuals and occupational groups requiring regular physical activity such as military cadets. RESULTS: 56 studies with 1874 athletes or physically active individuals were included. Using the Oxford level of evidence rating, included studies were 18 level I (32.1%), 3 level II (5.4%), 10 level III (17.9%), 13 level IV (23.2%) and 12 level V (21.4%). Based on the level I studies, ESWT may be effective alone in plantar fasciitis, lateral epicondylitis and proximal hamstring tendinopathy and as an adjunct to exercise treatment in medial tibial stress syndrome and osteitis pubis in athletes or physically active individuals. In most studies, athletes were allowed to continue activities and training and tolerated ESWT with minimal side effects. CONCLUSION: ESWT may offer an efficacious treatment alone or as an adjunct to concurrent exercise therapy in selected sports-related injuries and without major adverse events. Further high-level research is needed to better define the role and clinical outcomes of ESWT.

Utilizing Extracorporeal Shockwave Therapy for in-Season Athletes.

An athlete's health and availability to train and compete at an optimal performance level is a growing focus for professional sports organizations [...].

Platelet-Rich Plasma Applications for Achilles Tendon Repair: A Bridge between Biology and Surgery.

Achilles tendon ruptures are very common tendon ruptures and their incidence is increasing in modern society, resulting in work incapacity and months off sport, which generate a need for accelerated and successful therapeutic repair strategy. Platelet-rich plasma (PRP) is emerging as adjuvant human blood-derived constructs to assist Achilles tendon rupture treatment. However, myriad PRP preparation methods in conjunction with poor standardization in the modalities of their applications impinge on the consistent effectiveness of clinical and structural outcomes regarding their therapeutic efficacy. The purpose of this review is to provide some light on the application of PRP for Achilles tendon ruptures. PRP has many characteristics that make it an attractive treatment. Elements such as the inclusion of leukocytes and erythrocytes within PRP, the absence of activation and activation ex vivo or in vivo, the modality of application, and the adjustment of PRP pH can influence the biology of the applied product and result in misleading therapeutic conclusions. The weakest points in demonstrating their consistent effectiveness are primarily the result of myriad PRP preparation methods and the poor standardization of modalities for their application. Selecting the right biological scaffold and applying it correctly to restitutio ad integrum of ruptured Achilles tendons remains a daunting and complex task.

Platelet-rich plasma for the treatment of knee osteoarthritis: an expert opinion and proposal for a novel classification and coding system.

INTRODUCTION: Platelet-rich plasma (PRP) is able to modulate the joint environment by reducing the inflammatory distress and promoting tissue anabolism. Therefore, it has gained increasing popularity among clinicians in the treatment of osteoarthritis (OA), and it is currently proposed beside consolidated options such as viscosupplementation. AREAS COVERED: A systematic review of all available meta-analyses evaluating intra-articular PRP injections in patients affected by knee OA was performed, to understand how this biologic treatment approach compares to the traditional injective therapies available in clinical practice. Moreover, a novel coding system and 'minimum reporting requirements' are proposed to improve future research in this field and promote a better understanding of the mechanisms of action and indications. EXPERT OPINION: The main limitation in the current literature is the extreme variability of PRP products used, with often paucity or even lack of data on the biologic features of PRP, which should not be considered as a simple substance, but rather a 'procedure' requiring accurate reporting of the characteristics of the product but also all preparation and application modalities. This approach will aid in matching the optimal PRP product to specific patient factors, leading to improved outcomes and the elucidation of the cost-effectiveness of this treatment.

Collagenase Clostridium histolyticum for the Treatment of Distal Interphalangeal Joint Contractures in Dupuytren Disease.

PURPOSE: To explore the efficacy of injectable collagenase Clostridium histolyticum (CCH) in distal interphalangeal (DIP) joint contractures in Dupuytren disease. METHODS: A retrospective review was conducted for patients with DIP joint contractures treated with CCH. Baseline contracture and posttreatment residual contracture were recorded. The primary end point was achievement of 0° to 5° of residual contracture 30 days postmanipulation. Recurrence and adverse events are also reported. RESULTS: Twenty-one patients were treated with collagenase for DIP joint contractures and had a mean follow-up of 2.6 months. Seventeen of 21 patients reached the primary end point of less than 5° residual flexion contracture. Eleven of 21 patients experienced an adverse event, most commonly bruising and edema. No serious complications such as neurovascular injuries or tendon ruptures were recorded. Two patients had recurrence of disease. CONCLUSIONS: Injection with CCH is an option for the treatment of DIP joint contractures in Dupuytren disease. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Intra-articular bone marrow concentrate injection protocol: short-term efficacy in osteoarthritis.

AIM: Evaluate intra-articular injection of bone marrow concentrate (BMC), followed by platelet-rich plasma (PRP) injection at 8 weeks follow-up in moderate/severe osteoarthritis. DESIGN: Single center, retrospective Case Series (n = 125). METHODS: Bone marrow was aspirated/concentrated using a standardized technique. Patients received a single intra-articular injection of BMC, with follow-up injection of PRP at 8 weeks. RESULTS: Median absolute pain reduction in all joints was five points (71.4%) on visual analog scale. Median patient satisfaction was 9.0/10, while 91.7% indicated that they would repeat the procedure and 94% said that they would recommend the procedure to a friend. CONCLUSION: Intra-articular injection of BMC, followed by a PRP injection, can provide short-term benefits in moderate-to-severe osteoarthritis.

Stem cell therapies for treatment of cartilage and bone disorders: osteoarthritis, avascular necrosis, and non-union fractures.

The general ease of availability and strong fundamental science of autologous mesenchymal stem cells has prompted increasing application of such biologic therapies to address inherent orthopedic challenges of limited vascularity and ability to self-repair. This article provides a concise review of emerging mesenchymal stem cell applications for bone-related pathologies including cartilage, avascular necrosis, and fractures.

A call for a standard classification system for future biologic research: the rationale for new PRP nomenclature.

Autologous cell therapies including platelet-rich plasma (PRP) and bone marrow concentrate (BMC) are increasingly popular options for soft tissue and joint-related diseases. Despite increased clinical application, conflicting research has been published regarding the efficacy of PRP, and few clinical publications pertaining to BMC are available. Preparations of PRP (and BMC) can vary in many areas, including platelet concentration, number of white blood cells, presence or absence of red blood cells, and activation status of the preparation. The potential effect of PRP characteristics on PRP efficacy is often not well understood by the treating clinician, and PRP characteristics, as well as the volume of PRP delivered, are unfortunately not included in the methods of many published research articles. It is essential to establish a standard reporting system for PRP that facilitates communication and the interpretation and synthesis of scientific investigations. Herein, the authors propose a new PRP classification system reflecting important PRP characteristics based on contemporary literature and recommend adoption of minimal standards for PRP reporting in scientific investigations. Widespread adoption of these recommendations will facilitate interpretation and comparison of clinical studies and promote scientifically based progress in the field of regenerative medicine.

Efficacy of platelet-rich plasma for chronic tennis elbow: a double-blind, prospective, multicenter, randomized controlled trial of 230 patients.

BACKGROUND: Elbow tenderness and pain with resisted wrist extension are common manifestations of lateral epicondylar tendinopathy, also known as tennis elbow. Previous studies have suggested platelet-rich plasma (PRP) to be a safe and effective therapy for tennis elbow. PURPOSE: To evaluate the clinical value of tendon needling with PRP in patients with chronic tennis elbow compared with an active control group. STUDY DESIGN: Randomized controlled trial; Level of evidence, 2. METHODS: A total of 230 patients with chronic lateral epicondylar tendinopathy were treated at 12 centers over 5 years. All patients had at least 3 months of symptoms and had failed conventional therapy. There were no differences in patients randomized to receive PRP (n = 116) or active controls (n = 114). The PRP was prepared from venous whole blood at the point of care and contained both concentrated platelets and leukocytes. After receiving a local anesthetic, all patients had their extensor tendons needled with or without PRP. Patients and investigators remained blinded to the treatment group throughout the study. A successful outcome was defined as 25% or greater improvement on the visual analog scale for pain. RESULTS: Patient outcomes were followed for up to 24 weeks. At 12 weeks (n = 192), the PRP-treated patients reported an improvement of 55.1% in their pain scores compared with 47.4% in the active control group (P = .163). At 24 weeks (n = 119), the PRP-treated patients reported an improvement of 71.5% in their pain scores compared with 56.1% in the control group (P = .019). The percentage of patients reporting significant elbow tenderness at 12 weeks was 37.4% in the PRP group versus 48.4% in the control group (P = .143). Success rates for patients at 12 weeks were 75.2% in the PRP group versus 65.9% in the control group (P = .104). At 24 weeks, 29.1% of the PRP-treated patients reported significant elbow tenderness versus 54.0% in the control group (P = .009). Success rates for patients with 24 weeks of follow-up were 83.9% in the PRP group compared with 68.3% in the control group (P = .037). No significant complications occurred in either group. CONCLUSION: No significant differences were found at 12 weeks in this study. At 24 weeks, however, clinically meaningful improvements were found in patients treated with leukocyte-enriched PRP compared with an active control group.

Autologous bone marrow concentrate: review and application of a novel intra-articular orthobiologic for cartilage disease.

Younger adults, aged < 65 years, increasingly present to their physicians with advanced cartilage disease or post-traumatic osteoarthritis. A number of treatments exist for lessening patient pain and improving patient function. However, many patients are becoming aware of the potential of regenerative therapies and are now seeking solutions to the impaired biology underlying their conditions rather than addressing only their symptoms. Patients do not want to merely lessen their symptoms temporarily with a surgical procedure that replaces damaged tissue, but instead seek correction and repair of the underlying biology to regenerate damaged tissue and alleviate their symptoms altogether. Current therapies for patients with cartilage disease or osteoarthritis range from non-surgical intra-articular injections with biologics, such as hyaluronic acid (HA), to total joint arthroplasty for advanced stages of disease. Total joint arthroplasty is a successful procedure for patients aged > 65 years; however, the limited long-term durability of implanted prostheses decreases the preference of using such methods in more active patients aged < 65 years. The potential of cell-based orthobiologic injection therapies (pertaining to therapeutic injectables that aim to restore the biologic environment and/or structural components of diseased or damaged musculoskeletal tissue) is of tremendous interest for younger, more active patients, and is even more appealing in that such therapy can be delivered at point-of-care in the clinic during an office visit. Notably, the exponential rate of progress in biotechnology has allowed for immediate application of myriad novel therapies prior to clear evidence of benefit from randomized clinical trials. Orthobiologic intra-articular injection therapies include HA and platelet-rich plasma (PRP). We report on current, available findings for a third-generation intra-articular orthobiologic injectable therapy for cartilage disease, bone marrow concentrate (BMC). Bone marrow concentrate contains mesenchymal stem cells (MSCs), hematopoetic stem cells, platelets (containing growth factors), and cytokines. The anti-inflammatory and immunomodulatory properties of bone marrow stem cells (BMSCs) can facilitate regeneration of tissue. Additionally, BMSCs enhance the quality of cartilage repair by increasing aggrecan content and tissue firmness. Following bone marrow aspiration (BMA), BMC is easily prepared using centrifugation, and is available for a same-day procedure with minimal manipulation of cells, thus complying with US Food and Drug Association (FDA) restrictions. To date, there are no published randomized controlled trials on the efficacy of use of autologous BMC intra-articular injections performed as a same-day in-office procedure for treating patients with cartilage disease; however, several publications have reported the ease of use of this method, its strong safety profile, and the fundamental science suggesting great therapeutic potential.

Management of Dupuytren contracture with ultrasound-guided lidocaine injection and needle aponeurotomy coupled with osteopathic manipulative treatment.

Dupuytren contracture is a debilitating disease that characteristically presents as a firm nodularity on the palmar surface of the hand with coalescing cords of soft tissue on the webs and digits. With few nonsurgical modalities providing clinical benefits, open surgical procedures are the standard of care for patients with this condition. However, recent studies have associated surgical intervention with many complications, necessitating further exploration of nonsurgical treatment options. We describe the case of a 64-year-old woman who presented with decreased extension of the fourth and fifth digits on the upper extremities bilaterally; previous conservative treatment regimens had been unsuccessful. After a diagnostic ultrasound, the patient was diagnosed as having Dupuytren contracture and underwent 5 treatments consisting of ultrasound-guided dry-needle aponeurotomy, lidocaine injections, and osteopathic manipulative treatment. During the fifth treatment session, the patient experienced dramatic relief of her symptoms after a palpable release during the manual manipulation portion of her therapeutic regimen. At 2-week follow-up, the patient was symptom-free. Based on this desirable outcome, the authors suggest future research be directed at minimally invasive therapeutic options in the management of Dupuytren contracture.

Injection of platelet-rich plasma in patients with primary and secondary knee osteoarthritis: a pilot study.

OBJECTIVE: To evaluate the clinical effects of intraarticular platelet-rich plasma (PRP) injections in a small group of patients with primary and secondary osteoarthritis. Most of the current treatments for osteoarthritis are palliative and attack the symptoms rather than influencing the biochemical environment of the joint. Autologous platelet-rich plasma has emerged as a treatment option for tendinopathies and chronic wounds. In addition to release of growth factors, platelet-rich plasma also promotes concentrated anti-inflammatory signals including interleukin-1ra, which has been a focus of emerging treatments for osteoarthritis. DESIGN: In this single-center, uncontrolled, prospective preliminary study, 14 patients with primary and secondary knee osteoarthritis who met the study criteria received three platelet-rich plasma injections in the affected knee at ∼4-wk intervals. Outcome measures included the Brittberg-Peterson Visual Pain (Visual Analog Scale [VAS]), Activities, and Expectations score and the Knee Injury and Osteoarthritis Outcome Scores at preinjection visit at 2-, 5-, 11-, 18-, and 52-wk follow-up visits. Musculoskeletal ultrasound was used to measure cartilage thickness. RESULTS: There were no adverse events reported. The study demonstrated significant and almost linear improvements in Knee Injury and Osteoarthritis Outcome Scores, including pain and symptom relief. Brittberg-Peterson VAS showed many improvements including reduced pain after knee movement and at rest. Cartilage assessment was limited because of the small sample size. The majority of the patients expressed a favorable outcome at 12 mos after treatment. CONCLUSIONS: The positive trends and safety profile demonstrated could potentially be used to inspire a larger, blinded, and randomized clinical trial to determine whether platelet-rich plasma is safe and effective for the treatment of knee osteoarthritis.

Platelet rich plasma injection grafts for musculoskeletal injuries: a review.

In Europe and the United States, there is an increasing prevalence of the use of autologous blood products to facilitate healing in a variety of applications. Recently, we have learned more about specific growth factors, which play a crucial role in the healing process. With that knowledge there is abundant enthusiasm in the application of concentrated platelets, which release a supra-maximal quantity of these growth factors to stimulate recovery in non-healing injuries. For 20 years, the application of autologous PRP has been safely used and documented in many fields including; orthopedics, sports medicine, dentistry, ENT, neurosurgery, ophthalmology, urology, wound healing, cosmetic, cardiothoracic, and maxillofacial surgery. This article introduces the reader to PRP therapy and reviews the current literature on this emerging treatment modality. In summary, PRP provides a promising alternative to surgery by promoting safe and natural healing. However, there are few controlled trials, and mostly anecdotal or case reports. Additionally the sample sizes are frequently small, limiting the generalization of the findings. Recently, there is emerging literature on the beneficial effects of PRP for chronic non-healing tendon injuries including lateral epicondylitis and plantar fasciitis and cartilage degeneration (Mishra and Pavelko, The American Journal of Sports Medicine 10(10):1-5, 2006; Barrett and Erredge, Podiatry Today 17:37-42, 2004). However, as clinical use increases, more controlled studies are needed to further understand this treatment.

Experience with transtrapezium approach for transverse carpal ligament release in patients with coexisted trapeziometacarpal joint osteoarthritis and carpal tunnel syndrome.

An experience with transtrapezium approach for carpal tunnel release is reported. This technique seems to be successful in cases when carpal tunnel syndrome and first carpometacarpal joint osteoarthritis coexist and surgical treatment is indicated for both conditions. The transtrapezium approach to carpal tunnel release allows for complete carpal tunnel release without increasing the risk of surgical complications.

Percutaneous release of A1 pulley.

We performed 100 percutaneous releases of the trigger digits in a cadaveric model using an 18-gauge needle. Successful percutaneous release was achieved for only 59 digits (59%). No neurovascular injury occurred. We found that a percutaneous trigger digit release resulted in high percentage of incomplete releases of A1 pulley, especially in the thumb, index, and little fingers.

Recurrent enchondroma protuberans: a case report.

Enchondroma protuberans is a rare benign tumor. We present a case of late recurrence of a previously reported enchondroma protuberans in the hand. This was treated successfully with curettage and calcium carbonate grafting.

Giant cell tumour of the distal phalanx of the hand.

Giant cell tumour of bone in the phalanx of the hand is extremely rare. A case of giant cell tumour of distal phalanx treated with a ray amputation is presented.