An Initial Injection and a Crossover Injection of Amniotic Suspension Allograft Following Failed Treatment with Hyaluronic Acid or Saline Are Equally Effective in the Treatment of Moderate Symptomatic Knee Osteoarthritis Over 12 Months.

PURPOSE: The purpose of this crossover study was to determine the efficacy of amniotic suspension allograft (ASA) for moderate symptomatic knee osteoarthritis following failed treatment with hyaluronic acid (HA) or saline through 12 months' postcrossover injection using patient-reported and safety outcomes. METHODS: In this multicenter study, 95 patients from a 200-patient single-blind randomized controlled trial were eligible to crossover and receive a single injection of ASA 3 months after failed treatment with HA or saline. Patient-reported outcomes, including Knee Injury and Osteoarthritis Outcome Score (KOOS) and visual analog scale (VAS), were collected out to 12 months postcrossover to determine pain and function. Radiographs and blood were collected for assessment of changes. Statistical analyses were performed using mixed effects model for repeated measures. RESULTS: Treatment with ASA following failed treatment with HA or saline resulted in significant improvements in KOOS and VAS scores compared with crossover baseline. There were no differences in radiographic measures or anti-human leukocyte antigen serum levels compared with baseline and no severe adverse events reported. In addition, more than 55% of patients were responders at months 3, 6, and 12 as measured by the Outcome Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International simplified responder criteria. There were no significant differences between the original ASA randomized group and crossover cohorts at any of the time points evaluated, suggesting that prior failed treatment with HA or saline did not significantly impact outcomes following treatment with ASA. CONCLUSIONS: This study showed that patients who previously failed treatment with HA or saline had statistically significant improvements in pain and function scores following a crossover injection of ASA that was sustained for 12 months, as measured by KOOS and VAS. There were no serious adverse events reported, and the injection was safe. LEVEL OF EVIDENCE: II, prospective cohort study.

Hypothermically Stored Amniotic Membrane for the Treatment of Cartilage Lesions: A Single-Arm Prospective Study with 2-Year Follow-Up.

OBJECTIVE: The purpose of this study was to determine the safety and efficacy of hypothermically stored amniotic membrane (HSAM) for the treatment of cartilage lesions of the knee using imaging, patient-reported outcomes (PROs), second-look arthroscopy, and histology. Patients were treated with HSAM and followed for 2 years. DESIGN: Subjects with focal chondral lesions of the femur (International Cartilage Repair Society grade 3-4) were enrolled in this single-arm prospective study. Standard of care imaging was completed. PROs, including the Knee Injury and Osteoarthritis Outcome Score (KOOS), Marx Activity Scale, and Visual Analog Scale (VAS), were collected at baseline and at 3, 6, 12, 18, and 24 months. Three subjects underwent an optional arthroscopy and biopsy of the repair at 24 months. RESULTS: Ten subjects were enrolled and completed the study. At 24 months, KOOS Sports & Recreation improved 173.3% and Quality of Life improved 195.3% from baseline. Marx Activity Scale increased 266.8% from 12 to 24 months. VAS scores improved 84.8% and 81.0% from baseline to 24 months for average and maximum pain. Modified Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) scoring showed that 7 of 10 subjects had complete defect repair and filling by 24 months. Biopsy staining for collagen II revealed integration and remodeling of HSAM into a mix of hyaline-like cartilage and fibrocartilage matrix. CONCLUSION: This study provides evidence supporting the safety and efficacy of HSAM for treating symptomatic cartilage lesions. Subjects showed a high degree of defect fill and integration with the native cartilage and reported improvements in pain and function post-treatment. Results provide important original data for future clinical trials.

Editorial Commentary: Cell-Based Therapy for Treatment of Chondral Lesions of the Patellofemoral Joint Using Particulated Juvenile Chondrocytes.

The potential of cell-based therapies to fill articular cartilage defects is no longer a "pipe dream." Filling an articular cartilage defect with at least a "mixed hyaline cartilage" repair is no longer a question. The task at hand is somehow refining and defining the when, where, what, and how of the cartilage-growing procedures. The new ideas emerging are reflected in the recent literature, and all ideas regarding the specifics of these cartilage techniques and their outcomes should be welcomed. The information gained, that is, quality and quantity by magnetic resonance imaging and/or morphology (macro and micro), will allow the surgeon a choice as these techniques should certainly be part of a cartilage surgeon's armamentarium. No longer should microfracture and debridement be the only alternatives. Not only should we "save the meniscus" but we should also "save the articular cartilage."

Clinical, Radiographic, and Histological Outcomes After Cartilage Repair With Particulated Juvenile Articular Cartilage: A 2-Year Prospective Study.

BACKGROUND: Biological repair of cartilage lesions remains a significant clinical challenge because of the lack of natural regeneration and limited treatment options. HYPOTHESIS: Treatment of articular cartilage lesions in the knee with particulated juvenile articular cartilage (PJAC) will result in an improvement in patient symptoms of pain and function and magnetic resonance imaging (MRI) findings at 2 years compared with baseline. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Patients with symptomatic articular cartilage lesions on the femoral condyles or trochlear groove of the knee were identified for treatment with PJAC. There were 25 patients with a mean age of 37.0 ± 11.1 years and a mean lesion size of 2.7 ± 0.8 cm(2). All patients were assessed preoperatively (baseline) with a knee examination and surveys including the International Knee Documentation Committee (IKDC) subjective knee form, 100-mm visual analog scale (VAS) for pain, and Knee injury and Osteoarthritis Outcome Score (KOOS). Patients were followed at predetermined time points postoperatively through 2 years. Also, MRI was performed at baseline and at 3, 6, 12, and 24 months. At 2 years, patients were given the option of undergoing voluntary diagnostic arthroscopic surgery with cartilage biopsy to assess the histological appearance of the cartilage repair including safranin O staining for proteoglycans and immunostaining for type I and II collagen. RESULTS: Clinical outcomes demonstrated statistically significant increases at 2 years after surgery compared with baseline, with improvements seen as early as 3 months. Over the 24-month follow-up period, the IKDC score increased from a mean of 45.7 to 73.6, KOOS-pain score from 64.1 to 83.7, KOOS-symptoms score from 64.6 to 81.4, KOOS-activities of daily living score from 73.8 to 91.5, KOOS-sports and recreation score from 44.6 to 68.3, and KOOS-quality of life score from 31.8 to 59.9. The MRI results suggested that T2-weighted scores were returning to a level approximating that of normal articular cartilage by 2 years. Histologically, the repair tissue in biopsy samples from 8 patients was composed of a mixture of hyaline and fibrocartilage; immunopositivity for type II collagen was generally higher than for type I collagen, and there appeared to be excellent integration of the transplanted tissue with the surrounding native articular cartilage. Other than elective biopsies, there were no reoperations, although 1 graft delamination was reported at 24 months. CONCLUSION: This study demonstrates a rapid, safe, and effective treatment for cartilage defects. For the patient population investigated, the clinical outcomes of the PJAC technique showed a significant improvement over baseline, with histologically favorable repair tissue 2 years postoperatively.