Patellofemoral Cartilage Lesions Treated With Particulated Juvenile Allograft Cartilage: A Prospective Study With Minimum 2-Year Clinical and Magnetic Resonance Imaging Outcomes.

PURPOSE: To analyze the functional outcomes of patients treated with particulated juvenile articular cartilage (PJAC) for symptomatic articular cartilage lesions in the patellofemoral joint, correlates clinical outcomes with magnetic resonance imaging (MRI) appearance of the repair tissue using cartilage-sensitive quantitative T2-mapping. METHODS: All patients treated with PJAC for patellofemoral lesions were identified and prospectively followed with clinical outcome scores (International Knee Documentation Committee [IKDC], Knee Outcome Survey-Activities of Daily Living [KOS-ADL], and Marx Activity Scale [MAS]). Postoperative MRI scans using quantitative T2 mapping were obtained and interpreted by an independent musculoskeletal radiologist. RESULTS: Twenty-seven patients treated with PJAC for 30 full-thickness patellofemoral cartilage lesions were identified; mean postoperative follow-up was 3.84 years. Improvements from pre- to postoperative mean IKDC (45.9 vs 71.2, P < .001) and KOS-ADL (60.7 vs 78.8, P < .001) scores were observed; no significant change in MAS was seen (7.04 vs 7.17, P = .97). Advanced age, history of previous surgery, lesion location (patella vs trochlea), or concomitant tibial tubercle osteotomy did not affect outcome scores. Greater body mass index was associated with less improvement in KOS-ADL score. No patients required reoperation for graft-related issues. Lesion fill exceeding 67% by MRI assessment was noted in 69.2% of lesions; depth of lesion fill did not correlate with clinical outcomes. Quantitative T2-mapping revealed prolonged relaxation time at the graft site compared with adjacent normal cartilage at both deep and superficial zones. CONCLUSIONS: This study found significantly improved pain and function in patients treated with PJAC for symptomatic patellofemoral articular cartilage defects. No patients required reoperation for graft-related issues. Postoperative MRI revealed majority lesion fill in more than 69% of patients, but persistent morphologic differences between graft site and normal adjacent cartilage remain. Though we support PJAC use in this setting to improve patient subjective outcomes, improved appearance on postoperative imaging was not found to provide additional clinical benefit. LEVEL OF EVIDENCE: Level IV, case series.

Similar Outcomes After Osteochondral Allograft Transplantation in Anterior Cruciate Ligament-Intact and -Reconstructed Knees: A Comparative Matched-Group Analysis With Minimum 2-Year Follow-Up.

PURPOSE: To compare failure rates and clinical outcomes of osteochondral allograft transplantation (OCA) in anterior cruciate ligament (ACL)-intact versus ACL-reconstructed knees at midterm follow-up. METHODS: After a priori power analysis, a prospective registry of patients treated with OCA for focal chondral lesions ≥2 cm2 in size with minimum 2-year follow-up was used to match ACL-reconstructed knees with ACL-intact knees by age, sex, and primary chondral defect location. Exclusion criteria included meniscus transplantation, realignment osteotomy, or other ligamentous injury. Complications, reoperations, and patient responses to validated outcome measures were reviewed. Failure was defined by any procedure involving allograft removal/revision or conversion to arthroplasty. Kaplan-Meier analysis and multivariate Cox regression were performed to evaluate the association of ACL reconstruction (ACLR) with failure. RESULTS: A total of 50 ACL-intact and 25 ACL-reconstructed (18 prior, 7 concomitant) OCA patients were analyzed. The mean age was 36.2 years (range, 14-62 years). Mean follow-up was 3.9 years (range, 2-14 years). Patient demographics and chondral lesion characteristics were similar between groups. ACL-reconstructed patients averaged 2.2 ± 1.9 prior surgeries on the ipsilateral knee compared with 1.4 ± 1.4 surgeries for ACL-intact patients (P = .014). Grafts used for the last ACLR included bone-patellar tendon-bone autograft, hamstring autograft, Achilles tendon allograft, and tibialis allograft (data available for only 11 of 25 patients). At final follow-up, 22% of ACL-intact and 32% of ACL-reconstructed patients had undergone reoperation. OCA survivorship was 90% and 96% at 2 years and 79% and 85% at 5 years in ACL-intact and ACL-reconstructed patients, respectively (P = .774). ACLR was not independently associated with failure. Both groups demonstrated clinically significant improvements in the Short Form-36 pain and physical functioning, International Knee Documentation Committee subjective, and Knee Outcome Survey-Activities of Daily Living scores at final follow-up (P < .001), with no significant differences in preoperative, postoperative, and change scores between groups. CONCLUSIONS: OCA in the setting of prior or concomitant ACLR does not portend higher failure rates or compromise clinical outcomes. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

High Short-Term Failure Rate Associated With Decellularized Osteochondral Allograft for Treatment of Knee Cartilage Lesions.

PURPOSE: To report the short-term clinical and radiographic outcomes following the use of decellularized osteochondral (OC) allograft plugs in the treatment of distal femoral OC lesions. METHODS: An Institutional Review Board-approved database with prospectively collected data was used to identify patients treated with the decellularized OC allograft plugs implant. Demographic information, patient-reported outcomes, magnetic resonance imaging (MRI), and the number and type of reoperations were assessed. Failure was defined as revision surgery with removal of the implant. Patients were evaluated pre- and postoperatively using the Short Form-36, Activity of Daily Living Score, International Knee Documentation Committee Subjective Evaluation, Cincinnati Knee Rating System, and Marx Activity Scale. MRIs were evaluated using the OsteoChondral Allograft MRI Scoring System. RESULTS: Thirty-four patients were identified, with a mean age of 45 (±11.9) years; 71% were male. Fifteen (44%) patients had undergone prior ipsilateral surgical intervention. Mean defect size was 4 (±1.5) cm2, and median number of allografts per knee was 2 (range, 1-5). Mean follow-up duration was 15.5 months (range, 6-24). Ten patients (29%) required revision surgery with removal of the implant. Implant survivorship was 61% at 2 years. Female gender was independently predictive of failure, with a hazard ratio of 9.4 (95% confidence interval [CI], 2.0-58.9; P = .005). Defect size was also independently predictive of failure, with a hazard ratio of 1.9 per 1 cm2 increase (95% CI, 1.2-3.1; P = .005). MRIs obtained at 1 year postoperatively demonstrated significantly improved osseous integration (P = .0086) and opposing cartilage (P = .019) in the nonfailure group as compared with the failure group. CONCLUSIONS: Based on the high short-term failure rate observed in this study, the authors advise that a decellularized OC allograft plugs implant should be used with caution in the treatment of OC lesions of the knee, as similar outcomes have not been noted with other cartilage restoration techniques. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Osteochondral Allograft Transplantation of the Knee in Patients with an Elevated Body Mass Index.

OBJECTIVE: To characterize the graft survivorship and clinical outcomes of osteochondral allograft transplantation (OCA) of the knee in patients with an elevated body mass index (BMI). DESIGN: Prospective data on 38 consecutive patients with a BMI ≥30 kg/m2 treated with OCA from 2000 to 2015 were reviewed. Complications, reoperations, and patient responses to validated outcome measures were examined. Failures were defined by any removal/revision of the allograft or conversion to arthroplasty. RESULTS: Thirty-one knees in 31 patients (mean age, 35.4 years [range, 17-61 years]; 87% male) met the inclusion criteria. Mean BMI was 32.9 kg/m2 (range, 30-39 kg/m2). Mean chondral defect size was 6.4 cm2 (range, 1.0-15.3 cm2). Prior to OCA, 23 patients (74%) had undergone previous surgery to the ipsilateral knee. Mean duration of follow-up was 4.1 years (range, 2-11 years). After OCA, 5 knees (13%) underwent conversion to unicompartmental (1) or total (4) knee arthroplasty. Two- and 5-year graft survivorship were 87% and 83%, respectively. At final follow-up, clinically significant improvements were noted in the pain (49.3-72.6) and physical functioning (52.9-81.3) subscales of the Short Form-36 ( P ≤ 0.001), International Knee Documentation Committee subjective form (43.5-67.0; P = 0.002), Knee Outcome Survey-Activities of Daily Living (58.2-80.4; P = 0.002), and overall condition subscale of the Cincinnati Knee Rating System (4.7-6.9; P = 0.046). CONCLUSIONS: OCA can be a successful midterm treatment option for focal cartilage defects of the knee in select patients with a BMI ≥30 kg/m2.

Clinically Meaningful Improvement After Treatment of Cartilage Defects of the Knee With Osteochondral Grafts.

BACKGROUND: Mosaicplasty and fresh osteochondral allograft transplantation (OCA) are popular cartilage restoration techniques that involve the single-stage implantation of viable, mature hyaline cartilage-bone dowels into chondral lesions of the knee. Recently, there has been greater focus on what represents a clinically relevant change in outcomes reporting, and commonly applied metrics for measuring clinical significance include the minimal clinically important difference (MCID) and substantial clinical benefit (SCB). PURPOSE: To define the MCID and SCB after mosaicplasty or OCA for the International Knee Documentation Committee (IKDC) subjective form and Knee Outcome Survey-Activities of Daily Living (KOS-ADL) and to determine patient factors that are predictive of achieving the MCID and SCB after mosaicplasty or OCA. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 3. METHODS: An institutional cartilage registry was reviewed to identify patients who underwent mosaicplasty or OCA. The decision to perform either mosaicplasty or OCA was generally based on chondral defect size. The IKDC and KOS-ADL were administered preoperatively and at a minimum of 2 years postoperatively. Patient responses to the outcome measures were aggregated, and the MCID and SCB of these outcome scores were calculated with anchor-based methods. Multivariate analysis adjusted for age and sex was performed to identify patient factors predictive of achieving the MCID and SCB. RESULTS: Of the 372 eligible patients, 151 (41%) were lost to follow-up, 46 (12%) had incomplete preoperative outcome scores and 2 were treated with OCA of the tibia and therefore excluded. In total, 173 knees were analyzed (n = 173 patients; mean age, 33.0 years; 37% female). Seventy-five (43%) and 98 (57%) knees were treated with mosaicplasty and OCA, respectively. The mean ± SD MCIDs for the IKDC and KOS-ADL were 17 ± 3.9 and 10 ± 3.7, respectively. The SCBs for the IKDC and KOS-ADL were 30 ± 6.9 and 17 ± 3.9, respectively. Univariate analysis demonstrated no association between procedure (mosaicplasty or OCA) and likelihood of achieving the MCID or SCB. In the multivariate analysis, lower preoperative IKDC and KOS-ADL scores, higher preoperative Marx Activity Rating Scale scores, lower preoperative 36-Item Short Form Health Survey pain scores, and a history of ≤1 prior ipsilateral knee surgical procedure were predictive of achieving the MCID and/or SCB. CONCLUSION: These values can be used to define a clinically meaningful improvement for future outcome studies. For surgeons considering mosaicplasty or OCA for their patients, these results can help guide clinical decision making and manage patient expectations before surgery.

Clinical and MRI Outcomes of Fresh Osteochondral Allograft Transplantation After Failed Cartilage Repair Surgery in the Knee.

BACKGROUND: Fresh osteochondral allograft transplantation is an appealing option to address a failed cartilage repair surgical procedure, given the ability to treat large lesions and to address the subchondral osseous changes commonly seen in the revision setting. We hypothesized that osteochondral allograft transplantation after failed cartilage repair would result in low failure rates and improved function and that improved graft incorporation on postoperative magnetic resonance imaging (MRI) would correlate with a superior clinical outcome. METHODS: A retrospective review of prospectively collected data was used to identify 43 patients treated with fresh osteochondral allograft transplantation after a previous cartilage repair surgical procedure and having a minimum follow-up of 2 years. Clinical outcomes were evaluated using the Short Form-36 (SF-36) score, International Knee Documentation Committee (IKDC) Subjective Knee Score, Marx Activity Scale, Knee Outcome Survey-Activities of Daily Living (KOS-ADL) Questionnaire, Cincinnati Sports Activity Score, and Cincinnati Overall Symptom Assessment. Postoperative MRI scans were obtained at a mean time of 19.7 months and were independently reviewed by a musculoskeletal radiologist using the Osteochondral Allograft MRI Scoring System (OCAMRISS). RESULTS: At a mean 3.5-year follow-up after osteochondral allograft transplantation, significant improvements (p < 0.05) in SF-36 Physical Function, SF-36 Pain, KOS-ADL, IKDC Subjective Knee Score, and Cincinnati Overall Symptom Assessment were seen. Over 90% of grafts remained in situ at the time of the latest follow-up, although 17 knees (40%) underwent reoperation, the majority for arthroscopic debridement or manipulation for stiffness. Body mass index (BMI) of >30 kg/m was associated with worse clinical outcomes. The mean total OCAMRISS score demonstrated poorer allograft integration in patients with graft failure, but the total score did not meaningfully correlate with clinical outcome scores. However, better individual articular cartilage appearance and osseous integration subscores were associated with better clinical outcome scores. CONCLUSIONS: Significant improvements in pain and function were seen following fresh osteochondral allograft transplantation after failed cartilage repair, with an overall graft survival rate of >90%. Patients with greater bone and cartilage incorporation on MRI had superior clinical outcomes, although persistent osseous edema was frequently seen. We concluded that osteochondral allograft transplantation is an effective salvage treatment after failed cartilage repair and recommend further evaluation of techniques to optimize graft integration. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Osteochondral Allograft Transplantation of the Knee in Patients Aged 40 Years and Older.

BACKGROUND: Treatment of large chondral defects of the knee among patients aged ≥40 years remains a difficult clinical challenge owing to preexisting joint degeneration and the lack of treatment options short of arthroplasty. PURPOSE: To characterize the survivorship, predictors of failure, and clinical outcomes of osteochondral allograft transplantation (OCA) of the knee among patients aged ≥40 years. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Prospectively collected data were reviewed for 54 consecutive patients aged ≥40 years who were treated with OCA. Preoperative levels of osteoarthritis (according to Kellgren-Lawrence classification) and meniscal volume and quality were graded from review of radiographs and magnetic resonance imaging. Complications, reoperations, and patient responses to validated outcome measures were reviewed. A minimum follow-up of 2 years was required for analysis. Failure was defined by any removal or revision of the allograft or conversion to arthroplasty. RESULTS: Among 51 patients (mean age, 48 years; range, 40-63 years; 65% male), a total of 52 knees had symptomatic focal cartilage lesions (up to 2 affected areas) that were classified as Outerbridge grade 4 at the time of OCA and did not involve substantial bone loss requiring shell allografts or additional bone grafting. Mean duration of follow-up was 3.6 years (range, 2-11 years). After OCA, 21 knees (40%) underwent reoperation, including 14 failures (27%) consisting of revision OCA (n = 1), unicompartmental knee arthroplasty (n = 5), and total knee arthroplasty (n = 8). Mean time to failure was 33 months, and 2- and 4-year survivorship rates were 88% and 73%, respectively. Male sex (hazard ratio = 4.18, 95% CI = 1.12-27.13) and a higher number of previous ipsilateral knee operations (hazard ratio = 1.70 per increase in 1 surgical procedure, 95% CI = 1.03-2.83) were predictors of failure. A higher Kellgren-Lawrence osteoarthritis grade on preoperative radiographs was associated with higher failure rates in the Kaplan-Meier analysis but not the multivariate model. At final follow-up, clinically significant improvements were noted in the pain (mean score, 47.8 to 67.6) and physical functioning (56.8 to 79.1) subscales of the Short Form-36, as well as the International Knee Documentation Committee subjective form (45.0 to 63.6), Knee Outcome Survey-Activities of Daily Living (64.5 to 80.1), and overall condition statement (4.5 to 6.8) ( P < .001). No significant changes were noted for the Marx Activity Rating Scale (5.1 to 3.9, P = .789). CONCLUSION: A higher failure rate was found in this series of patients aged ≥40 years who were treated with OCA as compared with other studies of younger populations. However, for select older patients, OCA can be a good midterm treatment option for cartilage defects of the knee.

Condyle-Specific Matching Does Not Improve Midterm Clinical Outcomes of Osteochondral Allograft Transplantation in the Knee.

BACKGROUND: Condyle-specific matching for osteochondral allograft transplantation (OCA) pairs donor and recipient condyles in an attempt to minimize articular incongruity. While the majority of cartilage defects are located on the medial femoral condyle, lateral femoral condyles are more commonly available as a graft source. The purpose of this study was to compare the clinical outcomes of patients treated with non-orthotopic (lateral-to-medial condyle or medial-to-lateral condyle) OCA with those treated with traditional orthotopic (medial-to-medial condyle or lateral-to-lateral condyle) OCA. We hypothesized that clinical outcomes would be similar between groups at midterm follow-up. METHODS: A retrospective review of prospectively collected data on patients treated with OCA from 2000 to 2014 was conducted. Seventy-seven patients with a full-thickness cartilage defect of a femoral condyle were treated with either orthotopic (n = 50) or non-orthotopic (n = 27) OCA. A minimum follow-up of 2 years was required for analysis. Patients in each group were matched according to sex, age, and total chondral defect size. Reoperations and patient responses to validated outcome measures were reviewed. Failure was defined as any revision cartilage procedure or conversion to knee arthroplasty. RESULTS: The mean duration of follow-up was 4.0 years (range, 2 to 16 years). The orthotopic and non-orthotopic OCA groups were comparable in terms of demographics, the mean number of prior ipsilateral knee operations, and the percentage of concomitant procedures at baseline. Reoperation (p = 0.427) and failure (p = 0.917) rates did not differ significantly between groups. Both groups demonstrated significant increases in the Short Form-36 (SF-36) physical functioning and pain, International Knee Documentation Committee (IKDC), and Knee Outcome Survey-Activities of Daily Living (KOS-ADL) scores compared with baseline (p < 0.004). Outcome scores (baseline and postoperative) and change scores did not differ significantly between groups. CONCLUSIONS: Clinical outcomes do not differ between patients treated with orthotopic OCA and those treated with non-orthotopic OCA, suggesting that condyle-specific matching may not be necessary. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Arp2/3 complex inhibition radically alters lamellipodial actin architecture, suspended cell shape, and the cell spreading process.

Recent studies have investigated the dendritic actin cytoskeleton of the cell edge's lamellipodial (LP) region by experimentally decreasing the activity of the actin filament nucleator and branch former, the Arp2/3 complex. Here we extend these studies via pharmacological inhibition of the Arp2/3 complex in sea urchin coelomocytes, cells that possess an unusually broad LP region and display correspondingly exaggerated centripetal flow. Using light and electron microscopy, we demonstrate that Arp2/3 complex inhibition via the drug CK666 dramatically altered LP actin architecture, slowed centripetal flow, drove a lamellipodial-to-filopodial shape change in suspended cells, and induced a novel actin structural organization during cell spreading. A general feature of the CK666 phenotype in coelomocytes was transverse actin arcs, and arc generation was arrested by a formin inhibitor. We also demonstrate that CK666 treatment produces actin arcs in other cells with broad LP regions, namely fish keratocytes and Drosophila S2 cells. We hypothesize that the actin arcs made visible by Arp2/3 complex inhibition in coelomocytes may represent an exaggerated manifestation of the elongate mother filaments that could possibly serve as the scaffold for the production of the dendritic actin network.