Novel Treatment Options for Knee Cartilage Defects in 2023.

Articular cartilage lesions are a common injury that have become increasingly treatable with joint preservation procedures. Well-documented allograft and cellular treatments for these lesions are detailed elsewhere in this volume. This article discusses three new unique options for addressing these defects taking three different paths to address these complex injuries. Agili-C is an existing FDA- and EMEA-approved option using an acellular aragonite-based scaffold to treat both chondral and osteochondral lesions, with or without concurrent arthritis. Cartistem is a stem-cell-based product composed of culture-expanded allogeneic human umbilical cord blood-derived mesenchymal stem cells and hyaluronic acid hydrogel, which is in its final clinical trial stages in the United States, but already has regulatory approval in Korea. IMPACT and RECLAIM studies have shown the safety and efficacy of a new one-stage procedure utilizing autologous chondrons combined with allogeneic mesenchymal stem cells (MSCs) that can provide another effective single-stage treatment option.

High tibial osteotomy combined with cartilage restoration: A systematic review of clinical outcomes and prognostic factors.

Background: Focal chondral defects are often treated with cartilage restoration procedures. Malalignment often accompanies chondral defects. High tibial osteotomy (HTO), classically utilized to treat uni-compartmental knee osteoarthritis, corrects malalignment. HTO combined with cartilage restoration procedures can treat uni-compartmental osteoarthritis and focal chondral defects. Purpose: To assess outcomes of combined HTO and cartilage restoration procedures and review prognostic factors that may assist in preoperative planning and patient counseling. Study design: Systematic Review of published literature. Methods: A systematic review of PubMed and Scopus was performed following PRISMA guidelines. Thirty-four papers were included in qualitative considerations. Results: Thirty-four papers that reported the combined outcome of HTO and cartilage repair were included. Twenty of the 34 included papers reported prognostic factors that affected the success or failure of combined HTO and cartilage repair surgery for focal articular defect and uni-compartmental knee osteoarthritis. Cartilage repair techniques that were combined with HTO and included in this review are bone marrow stimulation, allograft transplantation, osteochondral autograft transplantation, autologous chondrocyte implantation, and mesenchymal stem cell implantation. Conclusions: HTO with adjunctive cartilage repair procedures improve clinical outcome scores and restore alignment in patients with medial compartment osteoarthritis and isolated focal chondral defects. HTO with adjunctive cartilage procedures produces optimal results in younger, non-obese patients with focal chondral defects and varus malalignment, without significant lateral compartment and patellofemoral involvement.

Experts Achieve Consensus on a Majority of Statements Regarding Platelet-Rich Plasma Treatments for Treatment of Musculoskeletal Pathology.

PURPOSE: To establish consensus statements on platelet-rich plasma (PRP) for the treatment of musculoskeletal pathologies. METHODS: A consensus process on the treatment of PRP using a modified Delphi technique was conducted. Thirty-five orthopaedic surgeons and sports medicine physicians participated in these consensus statements on PRP. The participants were composed of representatives of the Biologic Association, representing 9 international orthopaedic and musculoskeletal professional societies invited due to their active interest in the study of orthobiologics. Consensus was defined as achieving 80% to 89% agreement, strong consensus was defined as 90% to 99% agreement, and unanimous consensus was indicated by 100% agreement with a proposed statement. RESULTS: There was consensus on 62% of statements about PRP. CONCLUSIONS: (1) PRP should be classified based on platelet count, leukocyte count, red blood count, activation method, and pure-plasma versus fibrin matrix; (2) PRP characteristics for reporting in research studies are platelet count, leukocyte count, neutrophil count, red blood cell count, total volume, the volume of injection, delivery method, and the number of injections; (3) the prognostic factors for those undergoing PRP injections are age, body mass index, severity/grade of pathology, chronicity of pathology, prior injections and response, primary diagnosis (primary vs postsurgery vs post-trauma vs psoriatic), comorbidities, and smoking; (4) regarding age and body mass index, there is no minimum or maximum, but clinical judgment should be used at extremes of either; (5) the ideal dose of PRP is undetermined; and (6) the minimal volume required is unclear and may depend on the pathology. LEVEL OF EVIDENCE: Level V, expert opinion.

Exosome-Laden Scaffolds for Treatment of Post-Traumatic Cartilage Injury and Osteoarthritis of the Knee: A Systematic Review.

Mesenchymal stem cell (MSC)-based exosomes have garnered attention as a viable therapeutic for post-traumatic cartilage injury and osteoarthritis of the knee; however, efforts for application have been limited due to issues with variable dosing and rapid clearance in vivo. Scaffolds laden with MSC-based exosomes have recently been investigated as a solution to these issues. Here, we review in vivo studies and highlight key strengths and potential clinical uses of exosome-scaffold therapeutics for treatment of post-traumatic cartilage injury and osteoarthritis. In vivo animal studies were gathered using keywords related to the topic, revealing 466 studies after removal of duplicate papers. Inclusion and exclusion criteria were applied for abstract screening and full-text review. Thirteen relevant studies were identified for analysis and extraction. Three predominant scaffold subtypes were identified: hydrogels, acellular extracellular matrices, and hyaluronic acid. Each scaffold-exosome design showcased unique properties with relation to gross findings, tissue histology, biomechanics, and gene expression. All designs demonstrated a reduction in inflammation and induction of tissue regeneration. The results of our review show that current exosome-scaffold therapeutics demonstrate the capability to halt and even reverse the course of post-traumatic cartilage injury and osteoarthritis. While this treatment modality shows incredible promise, future research should aim to characterize long-term biocompatibility and optimize scaffold designs for human treatment.

Aragonite-Based Scaffold Versus Microfracture and Debridement for the Treatment of Knee Chondral and Osteochondral Lesions: Results of a Multicenter Randomized Controlled Trial.

BACKGROUND: Lesions of the articular cartilage, with or without involvement of the subchondral bone, are a common cause of pain and dysfunction in the knee. Although several treatment options have been developed, the majority of previous clinical trials examined patients with isolated or focal midsized defects, which rarely represent the condition found in the general population. Rather, cartilage lesions are often associated with the presence of mild to moderate osteoarthritic changes. PURPOSE: The present multicenter randomized controlled trial compared the clinical and radiographic outcomes of an aragonite-based osteochondral implant with a control group (arthroscopic debridement/microfractures) in patients affected by joint surface lesions of the knee, including those with concurrent mild to moderate osteoarthritis. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A total of 251 patients were enrolled in 26 medical centers according to the following criteria: age 21 to 75 years, up to 3 cartilage defects of International Cartilage Regeneration & Joint Preservation Society grade 3a or above located on the femoral condyles and/or trochlea, total treatable area from 1 to 7 cm2, bony defect depth ≤8 mm, and knee osteoarthritis grade 0 to 3 according to Kellgren-Lawrence score. Patients were randomized to the aragonite-based implant or debridement/microfracture control arm in a 2:1 ratio. Evaluation was performed at 6, 12, 18, and 24 months based on overall Knee injury and Osteoarthritis Outcome Score (KOOS) as the primary endpoint, and the KOOS subscales (Pain, Quality of Life, Activities of Daily Living), percentage of responders, and International Knee Documentation Committee (IKDC) subjective score as the secondary endpoints. Patients also underwent magnetic resonance imaging evaluation at 12 and 24 months to assess defect fill grade. Failures (ie, need for any secondary treatment) and adverse events were also recorded. RESULTS: The implant group showed a statistically superior outcome in the primary endpoint and all secondary endpoints at each follow-up. The magnitude of improvement in the implant group was twice as large as that in the control group in terms of mean KOOS improvement at 2 years. Responder rate (defined as at least a 30-point improvement in overall KOOS) was 77.8% in the implant group as opposed to 33.6% in the control (P < .0001). Statistically superior results were seen in the IKDC score as well. At 24 months, 88.5% of the implanted group had at least 75% defect fill on magnetic resonance imaging as compared with 30.9% of controls (P < .0001). The failure rate was 7.2% for the implant group versus 21.4% for control. CONCLUSION: This aragonite-based scaffold was safe and effective in the treatment of chondral and osteochondral lesions in the knee, including patients with mild to moderate osteoarthritis, and provided superior outcomes as compared with the control group. REGISTRATION: NCT03299959 (ClinicalTrials.gov identifier).

Editorial Commentary: Amniotic Orthopaedic Biologics: There's Hope If We Avoid Hype.

Amniotic products donated from mothers having live births have been in use for wound care and other medical uses for many years. Recent developments in regenerative sciences have suggested these products in solution or lyophilized forms may be useful for the treatment of inflammatory diseases such as chronic tendinopathies and osteoarthritis of joints. These products for these indications, however, are deemed human cells, tissues, or cellular or tissue-based products (otherwise known as HCTPs) in the "351" category, meaning that they need to have a biologic license to be marketed and sold in the United States, and to gain this license, one needs to go through the usual rigor of investigational new drug filing and phase 1, 2, and 3 trials to prove safety and efficacy. Although current clinical use of amniotic solution and lyophilized products is on hold through this study period, both basic science and clinical trial studies are building a convincing set of data that suggest broad possibilities for their uses in the future. To date, both animal and human studies have shown that a single injection of amniotic suspension allograft is safe, has not elicited any significant immune response, and has been shown to be effective in several prospective studies and at least one well-controlled randomized controlled human study for knee osteoarthritis when compared with both hyaluronic acid and placebo saline. Proteins in these harvested and processed tissue allografts are anti-inflammatory, anticatabolic, and proanabolic. Appropriate caution by the Food and Drug Administration in granting licenses for these indications should not dissuade basic scientists and physicians from pursuing further research into these interesting products.

Treatment of post-meniscectomy knee symptoms with medial meniscus replacement results in greater pain reduction and functional improvement than non-surgical care.

PURPOSE: Partial meniscectomy is a common orthopedic procedure intended to improve knee pain and function in patients with irreparable meniscal tears. However, 6-25% of partial meniscectomy patients experience persistent knee pain after surgery. In this randomized controlled trial (RCT) involving subjects with knee pain following partial meniscectomy, it was hypothesized that treatment with a synthetic medial meniscus replacement (MMR) implant provides significantly greater improvements in knee pain and function compared to non-surgical care alone. METHODS: In this prospective, multicenter RCT, subjects with persistent knee pain following one or more previous partial meniscectomies were randomized to receive either MMR or non-surgical care. This analysis evaluated the 1-year outcomes of this 2-year clinical trial. Patient-reported knee pain, function, and quality of life were measured using nine separate patient-reported outcomes. The primary outcomes were the pain subscale of the Knee injury and Osteoarthritis Outcome Score (KOOS) and the average of all five KOOS subscales (KOOS Overall). Treatment cessation was defined as permanent device removal in the MMR group and any surgical procedure to the index knee in the non-surgical care group. RESULTS: Treated subjects had a median age of 52 years old (range 30-69 years) and one or more previous partial meniscectomies at a median of 34 months (range 5-430 months) before trial entry. Among 127 subjects treated with either MMR (n = 61) or non-surgical care (n = 66), 11 withdrew from the trial or were lost to follow-up (MMR, n = 0; non-surgical care, n = 11). The magnitude of improvement from baseline to 1 year was significantly greater in subjects who received MMR in both primary outcomes of KOOS Pain (P = 0.013) and KOOS Overall (P = 0.027). Treatment cessation was reported in 14.5% of non-surgical care subjects and only 4.9% of MMR subjects (n.s.). CONCLUSION: Treatment with the synthetic MMR implant resulted in significantly greater improvements in knee pain, function, and quality of life at 1 year of follow-up compared to treatment with non-surgical care alone. LEVEL OF EVIDENCE: I.

Biologic Association Annual Summit: 2020 Report.

Interest and research in biologic approaches for tissue healing are exponentially growing for a variety of musculoskeletal conditions. The recent hype concerning musculoskeletal biological therapies (including viscosupplementation, platelet-rich plasma, and cellular therapies, or "stem cells") is driven by several factors, including demand by patients promising regenerative evidence supported by substantial basic and translational work, as well as commercial endeavors that complicate the scientific and lay understanding of biological therapy outcomes. While significant improvements have been made in the field, further basic and preclinical research and well-designed randomized clinical trials are needed to better elucidate the optimal indications, processing techniques, delivery, and outcome assessment. Furthermore, biologic treatments may have potential devastating complications when proper methods or techniques are ignored. For these reasons, an association comprising several scientific societies, named the Biologic Association (BA), was created to foster coordinated efforts and speak with a unified voice, advocating for the responsible use of biologics in the musculoskeletal environment in clinical practice, spearheading the development of standards for treatment and outcomes assessment, and reporting on the safety and efficacy of biologic interventions. This article will introduce the BA and its purpose, provide a summary of the 2020 first annual Biologic Association Summit, and outline the future strategic plan for the BA.

Safety and Efficacy of an Amniotic Suspension Allograft Injection Over 12 Months in a Single-Blinded, Randomized Controlled Trial for Symptomatic Osteoarthritis of the Knee.

PURPOSE: The purpose of this study is to determine the efficacy of amniotic suspension allograft (ASA) compared to hyaluronic acid (HA) and saline at up to 12 months of follow-up through the use of patient-reported outcomes, immunoglobulin levels, and anti-human leukocyte antigen (HLA) levels. METHODS: Within this multicenter study, 200 patients were randomized 1:1:1 to a single intra-articular injection of saline, HA, or ASA. Patient-reported outcomes, including Knee Injury and Osteoarthritis Outcome Score (KOOS) and visual analog scale (VAS) score, were collected at multiple time points (baseline, 1 week, 6 weeks, 3 months, 6 months) out to 12 months to assess improvements in pain and function. Radiographs at baseline and 12 months were taken to determine radiographic changes, while blood was collected at baseline, 6 weeks, and 6 months to determine changes in immunoglobulins and anti-HLA levels. Statistical analyses were performed using last observation carried forward and mixed effects model for repeated measures. RESULTS: Treatment with ASA resulted in significant improvements in KOOS and VAS scores that were maintained through 12 months (P < .05). Treatment with ASA resulted in a 63.2% responder rate at 12 months using the Outcome Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International simplified definition. There were no significant differences between groups for radiographic measures in the index knee, immunoglobulins, C-reactive protein, or anti-HLA serum levels (P > .05). The number and type of adverse events (AEs) reported for ASA were comparable to the HA injection group, while no treatment-emergent AEs were reported for the saline group. CONCLUSIONS: This randomized controlled trial of ASA vs HA and saline for the treatment of symptomatic knee osteoarthritis demonstrated clinically meaningful improved outcomes with ASA over the controls out to 12 months postinjection. No concerning immunologic or adverse reactions to the ASA injection were identified with regards to severe AEs, immunoglobulin, or anti-HLA levels. LEVEL OF EVIDENCE: Level I, randomized controlled multicenter trial.

Scaffolds for Knee Chondral and Osteochondral Defects: Indications for Different Clinical Scenarios. A Consensus Statement.

OBJECTIVE: To develop patient-focused consensus guidelines on the indications for the use of scaffolds to address chondral and osteochondral femoral condyle lesions. DESIGN: The RAND/UCLA Appropriateness Method (RAM) was used to develop patient-specific recommendations by combining the best available scientific evidence with the collective judgement of a panel of experts guided by a core panel and multidisciplinary discussers. A list of specific clinical scenarios was produced regarding adult patients with symptomatic lesions without instability, malalignment, or meniscal deficiency. Each scenario underwent discussion and a 2-round vote on a 9-point Likert-type scale (range 1-3 "inappropriate," 4-6 "uncertain," 7-9 "appropriate"). Scores were pooled to generate expert recommendations. RESULTS: Scaffold (chondral vs. osteochondral), patient characteristics (age and sport activity level), and lesion characteristics (etiology, size, and the presence of osteoarthritis [OA]) were considered to define 144 scenarios. The use of scaffold-based procedures was considered appropriate in all cases of chondral or osteochondral lesions when joints are not affected by OA, while OA joints presented more controversial results. The analysis of the evaluated factors showed a different weight in influencing treatment appropriateness: the presence of OA influenced 58.3% of the indications, while etiology, size, and age were discriminating factors in 54.2%, 29.2%, and 16.7% of recommendations, respectively. CONCLUSIONS: The consensus identified indications still requiring investigation, but also the convergence of the experts in several scenarios defined appropriate or inappropriate, which could support decision making in the daily clinical practice, guiding the use of scaffold-based procedures for the treatment of chondral and osteochondral knee defects.

Preliminary Results From a US Clinical Trial of a Novel Synthetic Polymer Meniscal Implant.

BACKGROUND: At least 760,000 outpatient meniscectomies are performed in the United States each year, making this the most common musculoskeletal procedure. However, meniscal resection can alter the joint biomechanics and overload the articular cartilage, which may contribute to degenerative changes and the need for knee replacement. Avoiding or delaying knee replacement is particularly important in younger or more active patients. Synthetic meniscal implants have been developed in an attempt to restore the natural joint biomechanics, alleviate pain and disability, and potentially minimize degenerative changes in patients who require meniscectomy. PURPOSE: To evaluate the preliminary results from 2 ongoing trials that are evaluating the safety and effectiveness of a synthetic polymer meniscal implant (NUsurface; Active Implants, LLC). STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: This was a preliminary analysis of the first 100 patients enrolled across 2 studies for 12 months: a single-arm, intervention-only study and a randomized controlled trial comparing the investigational meniscal implant with nonsurgical therapy. There were 65 patients in the implant group (30 randomized) and 35 in the control group. Outcomes included Knee injury and Osteoarthritis Outcome Score (KOOS) and adverse events (AEs) collected at baseline and follow-up visits of 6 weeks, 6 months, and 12 months. RESULTS: No statistically significant differences were found in baseline characteristics between the implant and control groups. At 12 months, follow-up KOOS data were available for 87% of the 100 included patients. Significantly greater improvements from baseline were observed in the implant group compared with controls in all KOOS subcomponents, except for symptoms (119%-177% greater improvement at 12 months). AEs were reported at similar rates between the 2 groups, with 12 AEs among 11 patients in the implant group (16.9%) versus 5 AEs among 5 patients (14.3%) in the control group (P = .99). CONCLUSION: These preliminary results suggest significant improvements in pain and function scores with the implant over nonsurgical therapy and a similar adverse event rate.

Optimizing Clinical Use of Biologics in Orthopaedic Surgery: Consensus Recommendations From the 2018 AAOS/NIH U-13 Conference.

Concern that misinformation from direct-to-consumer marketing of largely unproven "biologic" treatments such as platelet-rich plasma and cell-based therapies may erode the public trust and the responsible investment needed to bring legitimate biological therapies to patients have resulted in calls to action from professional organizations and governing bodies. In response to substantial patient demand for biologic treatment of orthopaedic conditions, the American Academy of Orthopaedic Surgeons convened a collaborative symposium and established a consensus framework for improving and accelerating the clinical evaluation, use, and optimization of biologic therapies for musculoskeletal diseases. The economic and disease burden of musculoskeletal conditions is high. Of the various conditions discussed, knee osteoarthritis was identified as a "serious condition" associated with substantial and progressive morbidity and emerged as the condition with the most urgent need for clinical trial development. It was also recognized that stem cells have unique characteristics that are not met by minimally manipulated mixed cell preparations. The work group recommended that minimally manipulated cell products be referred to as cell therapy and that the untested and uncharacterized nature of these treatments be clearly communicated within the profession, to patients, and to the public. Minimum standards for product characterization and clinical research should also be followed. A framework for developing clinical trials related to knee OA was agreed upon. In addition to recommendations for development of high-quality multicenter clinical trials, another important recommendation was that physicians and institutions offering biologic therapies commit to establishing high-quality patient registries and biorepository-linked registries that can be used for postmarket surveillance and quality assessments.

Outcomes of autologous chondrocyte implantation in study of the treatment of articular repair (STAR) patients with osteochondritis dissecans.

BACKGROUND: This is an analysis of the prospective Study of the Treatment of Articular Repair (STAR) to evaluate the effectiveness of autologous chondrocyte implantation (ACI) in a subset of adult patients with osteochondritis dissecans (OCD) knee lesions. HYPOTHESIS: Autologous chondrocyte implantation can improve clinical outcomes in patients with at least 1 chronic OCD lesion of the knee who failed a previous non-ACI cartilage repair treatment. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Forty patients with at least one failed non-ACI treatment for an OCD knee lesion received ACI in a multicenter study. The modified Cincinnati Knee Rating System, the Knee injury and Osteoarthritis Outcome Score (KOOS), and the Short-Form 36 Health Survey (SF-36) were used to assess patient outcomes at baseline and periodically to 48 months. Treatment failures, serious adverse events, and subsequent surgical procedures were recorded. RESULTS: Thirty-two (80%) patients completed the 48-month study. Autologous chondrocyte implantation treatment was successful in 85% of patients. Mean (± standard deviation) overall knee condition score (modified Cincinnati) was 3.1 ± 1.1 at baseline and 6.8 ± 2.0 at month 48. Clinically and statistically significant (P < .001) mean improvements from baseline to month 48 for the KOOS were as follows: 51.5 to 79.5 (pain), 54.8 to 77.9 (symptoms), 27.5 to 63.6 (sports and recreation ability), 63.5 to 86.7 (activities of daily living), and 21.9 to 59.6 (knee-related quality of life). The mean improvement (P < .001) in overall health assessed by the SF-36 was 35.4 to 45.5. Thirty-five percent (n = 14/40) of patients had a subsequent surgical procedure, most frequently debridement of the cartilage lesion. Treatment failure occurred in 6 of 32 (19%) patients. CONCLUSION: Patients with OCD of the knee had statistically significant pain reduction and functional improvement for up to 48 months after ACI, despite the complexity and severity of the osteochondral lesions.

New Frontiers for Cartilage Repair and Protection.

OBJECTIVE: Articular cartilage injury is common after athletic injury and remains a difficult treatment conundrum both for the surgeon and athlete. Although recent treatments for damage to articular cartilage have been successful in alleviating symptoms, more durable and complete, long-term articular surface restoration remains the unattained goal. In this article, we look at both new ways to prevent damage to articular surfaces as well as new techniques to recreate biomechanically sound and biochemically true articular surfaces once an athlete injures this surface. This goal should include reproducing hyaline cartilage with a well-integrated and flexible subchondral base and the normal zonal variability in the articular matrix. RESULTS: A number of nonoperative interventions have shown early promise in mitigating cartilage symptoms and in preclinical studies have shown evidence of chondroprotection. These include the use of glucosamine, chondroitin, and other neutraceuticals, viscosupplementation with hyaluronic acid, platelet-rich plasma, and pulsed electromagnetic fields. Newer surgical techniques, some already in clinical study, and others on the horizon offer opportunities to improve the surgical restoration of the hyaline matrix often disrupted in athletic injury. These include new scaffolds, single-stage cell techniques, the use of mesenchymal stem cells, and gene therapy. CONCLUSION: Although many of these treatments are in the preclinical and early clinical study phase, they offer the promise of better options to mitigate the sequelae of athletically induced cartilage.

Guidelines for the Design and Conduct of Clinical Studies in Knee Articular Cartilage Repair: International Cartilage Repair Society Recommendations Based on Current Scientific Evidence and Standards of Clinical Care.

OBJECTIVE: To summarize current clinical research practice and develop methodological standards for objective scientific evaluation of knee cartilage repair procedures and products. DESIGN: A comprehensive literature review was performed of high-level original studies providing information relevant for the design of clinical studies on articular cartilage repair in the knee. Analysis of cartilage repair publications and synopses of ongoing trials were used to identify important criteria for the design, reporting, and interpretation of studies in this field. RESULTS: Current literature reflects the methodological limitations of the scientific evidence available for articular cartilage repair. However, clinical trial databases of ongoing trials document a trend suggesting improved study designs and clinical evaluation methodology. Based on the current scientific information and standards of clinical care, detailed methodological recommendations were developed for the statistical study design, patient recruitment, control group considerations, study endpoint definition, documentation of results, use of validated patient-reported outcome instruments, and inclusion and exclusion criteria for the design and conduct of scientifically sound cartilage repair study protocols. A consensus statement among the International Cartilage Repair Society (ICRS) and contributing authors experienced in clinical trial design and implementation was achieved. CONCLUSIONS: High-quality clinical research methodology is critical for the optimal evaluation of current and new cartilage repair technologies. In addition to generally applicable principles for orthopedic study design, specific criteria and considerations apply to cartilage repair studies. Systematic application of these criteria and considerations can facilitate study designs that are scientifically rigorous, ethical, practical, and appropriate for the question(s) being addressed in any given cartilage repair research project.

A prospective study of autologous chondrocyte implantation in patients with failed prior treatment for articular cartilage defect of the knee: results of the Study of the Treatment of Articular Repair (STAR) clinical trial.

BACKGROUND: This is a prospective clinical study to assess the effectiveness of autologous chondrocyte implantation in patients who failed prior treatments for articular cartilage defects of the knee. HYPOTHESIS: Autologous chondrocyte implantation provides clinical benefit in patients with failed articular cartilage treatments. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: One hundred fifty-four patients with failed treatment for articular cartilage defects of the knee received autologous chondrocyte implantation in a multicenter, prospective study. Follow-up was 48 months. Outcomes included change from baseline in knee function, knee pain, quality of life, and overall health. Duration of benefit after autologous chondrocyte implantation was compared with the failed prior non-autologous chondrocyte implantation procedure. Safety information was recorded. Additional analyses were performed on the 2 major cohorts of prior procedures entered into the study, marrow-stimulation technique or debridement alone, to assess if there were any significant differences in baseline characteristics, outcomes, or prognosis between the 2 groups. RESULTS: One hundred twenty-six patients (82%) completed the protocol. Seventy-six percent of patients were treatment successes at study end, while 24% were deemed treatment failures. Preoperative mean knee pain score was 3.0 (SD, 1.8; 0 = severe, 10 = normal). Mean improvements were observed from baseline to all time points (P < .001) for all outcome measures. Preoperative to 48-month values, respectively, were as follows: On the Knee injury and Osteoarthritis Outcome Score subscales of pain: 48.7 to 72.2; other symptoms: 51.8 to 70.8; sports/recreation: 25.8 to 55.8; knee quality of life: 20.9 to 52.2; and activities of daily living: 58.6 to 81.0; on the Modified Cincinnati Overall Knee score: 3.3 to 6.3; on the visual analog scale: 28.8 to 69.9; and on the SF-36 Overall Physical Health: 33.0 to 44.4. Results did not differ between patients whose primary surgery had been a marrow-stimulating procedure and those whose primary procedure had been a debridement alone. The median difference in duration of benefit between autologous chondrocyte implantation and the failed non-autologous chondrocyte implantation prior procedure was at least 31 months (P < .001). Seventy-six patients (49%) had subsequent surgical procedure(s), predominantly arthroscopic. Need for a subsequent surgical procedure was not predictive of failure. CONCLUSION: Patients with moderate to large chondral lesions with failed prior cartilage treatments can expect sustained and clinically meaningful improvement in pain and function after autologous chondrocyte implantation. The subsequent surgical procedure rate observed in this study (49% overall; 40% related to autologous chondrocyte implantation) appears higher than generally reported after autologous chondrocyte implantation.