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Background: Although osteochondral allograft (OCA) transplantation has been a standard treatment for patients with osteochondral lesions, there is a disagreement in commercial payers' medical criteria regarding the definition of medical suitability and thus authorization for OCA transplantation. The primary goal of this study was to understand where consensus between a committee of experienced cartilage restoration surgeon scientists and payer policies existed and where there was significant disagreement., Methods: U.S. private payers were identified by reviewing health insurance market research literature. Medical criteria were then obtained from publicly available payer medical polices. A literature review was conducted to identify supporting evidence for consensus statements based on private payer medical criteria. The MOCA (Metrics of Osteochondral Allograft) Committee, 30 experienced surgeons and subject-matter experts in OCA transplantation, used a Likert scale of 1 (strongly disagree) to 5 (strongly agree) to rank each statement. The extent of agreement and disagreement among participants was measured for each statement. Consensus was defined as agreement or disagreement of >75%., Results: Fifty-seven statements regarding relevant medical criteria for OCA transplantation were included in the survey. All 30 MOCA Committee members completed the survey (100% response rate). Over half of the statements (52.6%) did not reach consensus. Of the remaining 27 statements that reached consensus, respondents agreed or strongly agreed with 16 statements, and disagreed or strongly disagreed with 11 statements. Inconsistent voting was observed for statements related to osteoarthritis, inflammation, and degenerative changes., Conclusions: Commercial payers are not consistent in the medical criteria used to define patient eligibility for authorization of OCA transplantation. In contrast, an expert panel of cartilage surgeons reached a consensus that OCA transplantation was clearly suitable for a variety of specific indications. This study demonstrates the need to standardize medical criteria for cartilage restoration based on the most current literature, as well as in conjunction with experienced cartilage restoration experts., Level of Evidence: Therapeutic Level V . See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/H181 )., (Copyright © 2022 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved.)

Objective: No studies currently exist with long-term follow-up of use of osteochondral allografting (OCA) for treatment of steroid-associated osteonecrosis of femoral condyles in young, active patients who wish to avoid total knee arthroplasty (TKA). We evaluate the extent to which fresh osteochondral allografts can (1) prevent or postpone need for prosthetic arthroplasty and (2) maintain long-term clinically meaningful decrease in pain and improvement in function at mean 11-year follow-up., Design: Twenty-five patients (33 knees) who underwent OCA transplantation for osteonecrosis of the knee between 1984 and 2013 were evaluated, including 22 females and 11 males with average age of 25 years (range, 16-48 years). Mean total allograft surface area was 10.6 cm 2 (range, 4.0-19.0 cm 2 ). Evaluation included International Knee Documentation Committee (IKDC) scores, Knee Society function (KS-F) score, and modified (for the knee) Merle d'Aubigné-Postel (18-point) score., Results: OCA survivorship was 90% at 5 years and 82% at 10 years. Twenty-eight of 33 knees (85%) avoided arthroplasty and 25 of 33 knees (73%) avoided other surgical intervention. Mean IKDC pain score improved ( P = 0.001) from 7.2 preoperatively to 2.8 at latest follow-up, mean IKDC function score increased ( P = 0.005) from 3.3 to 6.5, and mean IKDC total score improved ( P = 0.001) from 31.9 to 61.1. Mean KS-F score improved ( P = 0.003) from 61.7 to 87.5. Mean modified Merle d'Aubigné-Postel (18-point) score improved ( P < 0.001) from 11.4 to 15.1., Conclusions: Our findings suggest that OCA transplantation is a reasonable surgical treatment option for steroid-associated osteonecrosis of the femoral condyles, with durable long-term outcomes.

Background: The initial focus of cartilage restoration algorithms has been on the femur; however, the patellofemoral compartment accounts for 20% to 30% of significant symptomatic chondral pathologies. While patellofemoral compartment treatment involves a completely unique subset of comorbidities, with a comprehensive and thoughtful approach many patients may benefit from osteochondral allograft treatment., Purpose: To perform a systematic review of clinical outcomes and failure rates after osteochondral allograft transplantation (OCA) of the patellofemoral joint at a minimum 18-month follow-up., Study Design: Systematic review; Level of evidence, 4., Methods: A systematic review of the literature regarding the existing evidence for clinical outcomes and failure rates of OCA for patellofemoral joint chondral defects was performed with the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, PubMed, and MEDLINE from studies published between 1990 and 2017. Inclusion criteria were as follows: clinical outcomes and failure rates of OCA for the treatment of chondral defects in the patellofemoral joint, English language, minimum follow-up of 18 months, minimum study size of 5 patients, and human studies. The methodological quality of each study was assessed with a modified version of the Coleman methodology score., Results: The systematic search identified 8 studies with a total of 129 patients. The methods of graft procurement and storage time included fresh (121 patients, 93.8%), and cryopreserved (8 patients, 6.2%) grafts. The mean survival rate was 87.9% at 5 years and 77.2% at 10 years. The following outcome scores showed significant improvement from pre- to postoperative status: modified d'Aubigné-Postel, International Knee Documentation Committee, Knee Society Score-Function, and Lysholm Knee Score., Conclusion: OCA of the patellofemoral joint results in improved patient-reported outcome measures with high patient satisfaction rates. Five- and 10-year survival rates of 87.9% and 77.2%, respectively, can be expected after this procedure. These findings should be taken with caution, as a high percentage of patellofemoral osteochondral allografts were associated with concomitant procedures; therefore, further research is warranted to determine the effect of isolated osteochondral transplantations.

Background: Osteochondral allograft (OCA) transplantation is an integral part of the cartilage repair paradigm, but insufficient data are available regarding return to sport or recreational activity after the procedure., Purpose: The purpose of this study was to determine if athletic patients undergoing OCA transplantation returned to sport, assess reasons for not returning to sport, and ascertain patient and graft-related characteristics that differed between those who returned or did not return to sport. The secondary aims were to assess graft survivorship and patient-reported subjective outcome measures (pain, function, satisfaction) among athletic patients undergoing OCA transplantation., Study Design: Case series; Level of evidence, 4., Methods: We identified 149 knees in 142 patients who participated in sport or recreational activity before a cartilage injury (45% highly competitive athletes and 55% well-trained and frequently sporting) and underwent OCA transplantation in the knee. The mean age was 31.2 years and 58.4% were male. Information on preinjury and postoperative participation in sport or recreational activity was collected. Patients not returning to sport after OCA transplantation were mailed a questionnaire to assess why. Postoperative pain, function, and satisfaction scores were obtained, and further surgery on the operative knee was documented., Results: At a mean follow-up of 6 years, 75.2% of knees returned to sport or recreational activity. Among those who did not return to sport, knee-related issues and lifestyle changes were cited as reasons why. Patients who did not return to sport were more likely to be female, have injured their knee in an activity other than sport, and have a larger graft size. The diagnosis and anatomic location also differed. Overall, 71% of knees reported having "very good" to "excellent" function, and 79% were able to participate in a high level of activity (moderate, strenuous, or very strenuous) postoperatively. After OCA transplantation, 25.5% of knees underwent further surgery; 14 knees (9.4% of entire cohort) were considered allograft failures. Among the 135 knees that had the graft remaining in situ, pain and function improved from preoperatively to the latest follow-up on all measures, and 91% of patients were satisfied with the results of the surgery., Conclusion: OCA transplantation is a successful treatment option for athletes and highly active patients who sustain a cartilage injury to their knee. The majority of patients returned to sport or recreational activity.

Introduction: Osteochondral allograft (OCA) transplantation is generally effective for treating large cartilage lesions. Cleansing OCA subchondral bone to remove donor marrow elements is typically performed with pulsed lavage. However, the effects of clinical and experimental parameters on OCA marrow removal by pulsed lavage are unknown. The aim of the current study was to determine the effects on marrow cleansing in human osteochondral cores (OCs) of (1) lavage duration, (2) lavage flow intensity, and (3) OC sample type and storage condition., Methods: OCs were harvested from human femoral condyles and prepared to a clinical geometry (cylinder, diameter = 20 mm). The OCs were from discarded remnants of Allograft tissues (OCA) or osteoarthritis patients undergoing Total Knee Replacement (OCT). The experimental groups subjected to standard flow lavage for 45 seconds (430 mL of fluid) and 120 seconds (1,150 mL) were (1) OCT/FROZEN (stored at -80°C), (2) OCT/FRESH (stored at 4°C), and (3) OCA/FRESH. The OCA/FRESH group was subsequently lavaged at high flow for 45 seconds (660 mL) and 120 seconds (1,750 mL). Marrow cleansing was assessed grossly and by micro-computed tomography (μCT)., Results: Gross and μCT images indicated that marrow cleansing progressed from the OC base toward the cartilage. Empty marrow volume fraction (EMa.V/Ma.V) increased between 0, 45, and 120 seconds of standard flow lavage, and varied between groups, being higher after FROZEN storage (86-92% after 45-120 seconds) than FRESH storage of either OCT or OCA samples (36% and 55% after 45 and 120 seconds, respectively). With a subsequent 120 seconds of high flow lavage, EMa.V/Ma.V of OCA/FRESH samples increased from 61% to 78%., Conclusions: The spatial and temporal pattern of marrow space clearance was consistent with gradual fluid-induced extrusion of marrow components. Pulsed lavage of OCAs with consistent time and flow intensity will help standardize marrow cleansing and may improve clinical outcomes.

The treatment of articular cartilage injury and disease has become an increasingly relevant part of orthopaedic care. Articular cartilage transplantation, in the form of osteochondral allografting, is one of the most established techniques for restoration of articular cartilage. Our research efforts over the last two decades have supported the transformation of this procedure from experimental "niche" status to a cornerstone of orthopaedic practice. In this Kappa Delta paper, we describe our translational and clinical science contributions to this transformation: (1) to enhance the ability of tissue banks to process and deliver viable tissue to surgeons and patients, (2) to improve the biological understanding of in vivo cartilage and bone remodeling following osteochondral allograft (OCA) transplantation in an animal model system, (3) to define effective surgical techniques and pitfalls, and (4) to identify and clarify clinical indications and outcomes. The combination of coordinated basic and clinical studies is part of our continuing comprehensive academic OCA transplant program. Taken together, the results have led to the current standards for OCA processing and storage prior to implantation and also novel observations and mechanisms of the biological and clinical behavior of OCA transplants in vivo. Thus, OCA transplantation is now a successful and increasingly available treatment for patients with disabling osteoarticular cartilage pathology., (© 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Background: The treatment of patellofemoral cartilage injuries can be challenging. Osteochondral allograft (OCA) transplantation has been used as a treatment option for a range of cartilage disorders., Purpose: To evaluate functional outcomes and survivorship of the grafts among patients who underwent OCA for patellar cartilage injuries., Study Design: Case series; Level of evidence, 4., Methods: An institutional review board-approved OCA database was used to identify 27 patients (28 knees) who underwent isolated OCA transplantation of the patella between 1983 and 2010. All patients had a minimum 2-year follow-up. The mean age of the patients was 33.7 years (range, 14-64 years); 54% were female. Twenty-six (92.9%) knees had previous surgery (mean, 3.2 procedures; range, 1-10 procedures). The mean allograft area was 10.1 cm(2) (range, 4.0-18.0 cm(2)). Patients returned for clinical evaluation or were contacted via telephone for follow-up. The number and type of reoperations were assessed. Any reoperation resulting in removal of the allograft was considered a failure of the OCA transplantation. Patients were evaluated pre- and postoperatively using the modified Merle d'Aubigné-Postel (18-point) scale, the International Knee Documentation Committee (IKDC) pain, function, and total scores, and the Knee Society function (KS-F) score. Patient satisfaction was assessed at latest follow-up., Results: Seventeen of the 28 knees (60.7%) had further surgery after the OCA transplantation; 8 of the 28 knees (28.6%) were considered OCA failures (4 conversions to total knee arthroplasty, 2 conversions to patellofemoral knee arthroplasty, 1 revision OCA, 1 patellectomy). Patellar allografting survivorship was 78.1% at 5 and 10 years and 55.8% at 15 years. Among the 20 knees (71.4%) with grafts in situ, the mean follow-up duration was 9.7 years (range, 1.8-30.1 years). Pain and function improved from the preoperative visit to latest follow-up, and 89% of patients were extremely satisfied or satisfied with the results of the OCA transplantation., Conclusion: OCA transplantation was successful as a salvage treatment procedure for cartilage injuries of the patella., (© 2015 The Author(s).)

Background: Osteochondral allograft (OCA) transplantation is an effective treatment option for chondral and osteochondral defects of the knee., Hypothesis: Patients treated with OCAs for reciprocal bipolar lesions of the knee would demonstrate significant clinical improvement., Study Design: Case series; Level of evidence, 4., Methods: Between 1983 and 2010, OCAs were implanted for bipolar chondral lesions in 46 patients (48 knees). The 21 male and 25 female patients averaged 40 years of age (range, 15-66 years). Thirty-four lesions were tibiofemoral, and 14 were patellofemoral. Forty-two knees (88%) had undergone a mean of 3.4 previous surgeries (range, 1-8). The mean allograft area was 19.2 cm(2). Clinical evaluation included the modified Merle d'Aubigné-Postel (18-point), International Knee Documentation Committee (IKDC) pain and function, and Knee Society function (KS-F) scores. Further surgeries on the operative joint were documented., Results: Survivorship of the bipolar OCA was 64.1% at 5 years. Thirty knees underwent further surgery; 22 knees (46%) were considered failures (3 OCA revisions, 14 total knee arthroplasties, 2 unicondylar arthroplasties, 2 arthrodeses, and 1 patellectomy). Among patients whose OCA was still in situ at follow-up, the mean follow-up was 7 years (range, 2.0-19.7 years). The mean 18-point score improved from 12.1 to 16.1; 88% (23/26 knees) of surviving allografts scored ≥15. The mean IKDC pain score improved from 7.5 to 4.7, and the mean IKDC function score improved from 3.4 to 7.0. The mean KS-F score improved from 70.5 to 84.1., Conclusion: Osteochondral allograft transplantation is a useful salvage treatment option for reciprocal bipolar cartilage lesions of the knee. High reoperation and failure rates were observed, but patients with surviving allografts showed significant clinical improvement., (© 2015 The Author(s).)

Background: Multiple studies in adults have shown that osteochondral allograft transplantation is an effective treatment option for large chondral and osteochondral defects of the knee. Limited outcome data are available on osteochondral allografts in the pediatric and adolescent patient populations., Purpose: To describe a 28-year experience with osteochondral allograft transplantation in patients younger than 18 years with a focus on subjective outcome measures, return to activities, and allograft survivorship., Study Design: Case series; Level of evidence, 4., Methods: A total of 39 patients (43 knees) underwent fresh osteochondral allograft transplantation for treatment of chondral and osteochondral lesions. Twenty-six male and 17 female knees with a mean age of 16.4 years (range, 11.0-17.9 years) at index surgery were followed-up at a mean of 8.4 years (range, 1.7-27.1 years). Thirty-four knees (79%) had at least 1 previous surgery. The most common underlying causes of the lesions were osteochondritis dissecans (61%), avascular necrosis (16%), and traumatic chondral injury (14%). Mean allograft size was 8.4 cm(2). The most common allograft location was the medial femoral condyle (41.9%), followed by the lateral femoral condyle (35%). Each patient was evaluated with the International Knee Documentation Committee pain, function, and total scores; a modified Merle d'Aubigné-Postel (18-point) scale; and Knee Society function score. Failure was defined as revision osteochondral allograft or conversion to arthroplasty., Results: Five knees experienced clinical failure at a median of 2.7 years (range, 1.0-14.7 years). Four failures were salvaged successfully with another osteochondral allograft transplant. One patient underwent prosthetic arthroplasty 8.6 years after revision allograft. Graft survivorship was 90% at 10 years. Of the knees whose grafts were in situ at latest follow-up, 88% were rated good/excellent (18-point scale). The mean International Knee Documentation Committee scores improved from 42 preoperatively to 75 postoperatively, and the Knee Society function score improved from 69 to 89 (both P < .05). Eighty-nine percent of patients reported "extremely satisfied" or "satisfied.", Conclusion: With 88% good/excellent results and 80% salvage rate of clinical failures with an additional allograft, osteochondral allograft transplantation is a useful treatment option in pediatric and adolescent patients.

The efficacy of osteochondral allografts (OCAs) may be affected by osseous support of the articular cartilage, and thus affected by bone healing and remodeling in the OCA and surrounding host. Bone cysts, and their communication pathways, may be present in various locations after OCA insertion and reflect distinct pathogenic mechanisms. Previously, we analyzed the effect of OCA storage (FRESH, 4°C/14d, 4°C/28d, FROZEN) on cartilage quality in fifteen adult goats after 12months in vivo. The objectives of this study were to further analyze OCAs and contralateral non-operated (Non-Op) CONTROLS from the medial femoral condyle to (1) determine the effect of OCA storage on local subchondral bone (ScB) and trabecular bone (TB) structure, (2) characterize the location and structure of bone cysts and channels, and (3) assess the relationship between cartilage and bone properties. (1) Overall bone structure after OCAs was altered compared to Non-Op, with OCA samples displaying bone cysts, ScB channels, and ScB roughening. ScB BV/TV in FROZEN OCAs was lower than Non-Op and other OCAs. TB BV/TV in FRESH, 4°C/14d, and 4°C/28d OCAs did not vary compared to Non-Op, but BS/TV was lower. (2) OCAs contained "basal" cysts, localized to deeper regions, some "subchondral" cysts, localized near the bone-cartilage interface, and some ScB channels. TB surrounding basal cysts exhibited higher BV/TV than Non-Op. (3) Basal cysts occurred (a) in isolation, (b) with subchondral cysts and ScB channels, (c) with ScB channels, or (d) with subchondral cysts, ScB channels, and ScB erosion. Deterioration of cartilage gross morphology was strongly associated with abnormal μCT bone structure. Evidence of cartilage-bone communication following OCA repair may favor fluid intrusion as a mechanism for subchondral cyst formation, while bone resorption at the graft-host interface without affecting overall bone and cartilage structure may favor bony contusion mechanism for basal cyst formation. These findings suggest that cysts occurring after OCAs may result from aberrant mechanobiology due to (1) altered compartmentalization that normally separates overlying cartilage and subchondral bone, either from distinct ScB channels or more general ScB plate deterioration, and (2) bone resorption at the basal graft-host interface., (© 2013.)

The long-term efficacy of osteochondral allografts is due to the presence of viable chondrocytes within graft cartilage. Chondrocytes in osteochondral allografts, especially those at the articular surface that normally produce the lubricant proteoglycan-4 (PRG4), are susceptible to storage-associated death. The hypothesis of this study was that the loss of chondrocytes within osteochondral grafts leads to decreased PRG4 secretion, after graft storage and subsequent implant. The objectives were to determine the effect of osteochondral allograft treatment (FROZEN vs. FRESH) on secretion of functional PRG4 after (i) storage, and (ii) 6 months in vivo in adult goats. FROZEN allograft storage reduced PRG4 secretion from cartilage by ∼85% compared to FRESH allograft storage. After 6 months in vivo, the PRG4-secreting function of osteochondral allografts was diminished with prior FROZEN storage by ∼81% versus FRESH allografts and by ∼84% versus non-operated control cartilage. Concomitantly, cellularity at the articular surface in FROZEN allografts was ∼96% lower than FRESH allografts and non-operated cartilage. Thus, the PRG4-secreting function of allografts appears to be maintained in vivo based on its state after storage. PRG4 secretion may be not only a useful marker of allograft performance, but also a biological process protecting the articular surface of grafts following cartilage repair., (Copyright © 2013 Orthopaedic Research Society.)

Background: Understanding the effectiveness of frozen as compared with fresh osteochondral allografts at six months after surgery and the resultant consequences of traditional freezing may facilitate in vivo maintenance of cartilage integrity. Our hypothesis was that the state of the allograft at implantation affects its performance after six months in vivo., Methods: The effect of frozen as compared with fresh storage on in vivo allograft performance was determined for osteochondral allografts that were transplanted into seven recipient goats and analyzed at six months. Allograft performance was assessed by examining osteochondral structure (cartilage thickness, fill, surface location, surface degeneration, and bone-cartilage interface location), zonal cartilage composition (cellularity, matrix content), and cartilage biomechanical function (stiffness). Relationships between cartilage stiffness or cartilage composition and surface degeneration were assessed with use of linear regression., Results: Fresh allografts maintained cartilage load-bearing function, while also maintaining zonal organization of cartilage cellularity and matrix content, compared with frozen allografts. Overall, allograft performance was similar between fresh allografts and nonoperative controls. However, cartilage stiffness was approximately 80% lower (95% confidence interval [CI], 73% to 87%) in the frozen allografts than in the nonoperative controls or fresh allografts. Concomitantly, in frozen allografts, matrix content and cellularity were approximately 55% (95% CI, 22% to 92%) and approximately 96% (95% CI, 94% to 99%) lower, respectively, than those in the nonoperative controls and fresh allografts. Cartilage stiffness correlated positively with cartilage cellularity and matrix content, and negatively with surface degeneration., Conclusions: Maintenance of cartilage load-bearing function in allografts is associated with zonal maintenance of cartilage cellularity and matrix content. In this animal model, frozen allografts displayed signs of failure at six months, with cartilage softening, loss of cells and matrix, and/or graft subsidence, supporting the importance of maintaining cell viability during allograft storage and suggesting that outcomes at six months may be indicative of long-term (dys)function., Clinical Relevance: Fresh versus frozen allografts represent the "best versus worst" conditions with respect to chondrocyte viability, but "difficult versus simple" with respect to acquisition and distribution. The outcomes described from these two conditions expand the current understanding of in vivo cartilage remodeling and describe structural properties (initial graft subsidence), which may have implications for impending graft failure.

Background: Currently, osteochondral allografts (OCA) are typically used after 4°C storage for prolonged durations (15-43 days), which compromises chondrocyte viability, especially at the articular surface. The long-term in vivo performance of these fresh-stored allografts, in association with variable cellularity, is unknown., Purpose: To determine the effect of 4°C storage duration (14, 28 days) versus the best (fresh) and worst (frozen) conditions of chondrocyte viability on structure, composition, and function of cartilage in the goat and the association of retrieved chondrocyte cellularity with those tissue properties., Study Design: Controlled laboratory study., Methods: The effect of allograft storage on in vivo repair outcomes was determined for OCA transplanted into 15 recipient goats and analyzed at 12 months. Repair outcomes were assessed by examining cartilage structure (gross, histopathology), composition (cellularity by depth, matrix fixed charge), and biomechanical function (stiffness). Relationships between cellularity and structural scores, matrix fixed charge, and stiffness were assessed by linear regression., Results: Repair outcomes in 4°C-stored OCA were similar after 14 and 28 days of storage, and both were inferior to fresh OCA and were accompanied by diminished cellularity at the surface, matrix fixed charge, and histopathological structure. Overall, cellularity by depth and matrix fixed charge in cartilage of fresh OCA were similar to nonoperated controls. However, cellularity at the articular surface and matrix fixed charge in 4°C-stored OCA were lower than fresh, by ~55% (95% confidence interval [CI], 32%-76%) and ~20% (CI, 9%-30%), respectively. In frozen OCA, cellularity and matrix fixed charge were lower than 4°C-stored OCA, by ~93% (CI, 88%-99%) and ~22% (CI, 10%-35%), respectively. Cellularity correlated negatively with cartilage health indices, including structural scores, and positively with matrix fixed charge and stiffness., Conclusion: Reduced cellularity at the articular surface, resulting from 4°C storage, was associated with variable long-term outcomes versus consistently good repair by fresh allografts. Cellularity at the articular surface was an important index of biological performance., Clinical Relevance: Normal chondrocyte density in vivo, especially in the superficial region of cartilage, is important for maintaining long-term cartilage function and matrix content. In human cartilage, containing cells at ~3 to 5 times lower density than goat, repair outcomes may be related to absolute minimum number of cells rather than density.

Objective: To determine if selected culture conditions enhance the expansion and redifferentiation of chondrocytes isolated from human osteoarthritic cartilage with yields appropriate for creation of constructs for treatment of joint-scale cartilage defects, damage, or osteoarthritis., Methods: Chondrocytes isolated from osteoarthritic cartilage were analyzed to determine the effects of medium supplement on cell expansion in monolayer and then cell redifferentiation in alginate beads. Expansion was assessed as cell number estimated from DNA, growth rate, and day of maximal growth. Redifferentiation was evaluated quantitatively from proteoglycan and collagen type II content, and qualitatively by histology and immunohistochemistry., Results: Using either serum or a growth factor cocktail (TFP: transforming growth factor beta1, fibroblast growth factor 2, and platelet-derived growth factor type bb), cell growth rate in monolayer was increased to 5.5x that of corresponding conditions without TFP, and cell number increased 100-fold within 17 days. In subsequent alginate bead culture with human serum or transforming growth factor beta1 and insulin-transferrin-selenium-linoleic acid-bovine serum albumin, redifferentiation was enhanced with increased proteoglycan and collagen type II production. Effects of human serum were dose dependent, and 5% or higher induced formation of chondron-like structures with abundant proteoglycan-rich matrix., Conclusion: Chondrocytes from osteoarthritic cartilage can be stimulated to undergo 100-fold expansion and then redifferentiation, suggesting that they may be useful as a cell source for joint-scale cartilage tissue engineering.

Background: Osteochondral grafts, used to treat chondral and osteochondral defects, require high insertional forces that may affect the viability of chondrocytes in the graft. The objectives of this study were to (1) measure the loading impact during insertion of osteochondral grafts, (2) evaluate the effect of insertional loading on chondrocyte viability, and (3) assess this effect on chondrocyte apoptosis and activation of caspase-3., Methods: The distal parts of twelve fresh femora from six adult human cadavers were harvested within seventy-two hours after the death of the donor. From each femur, four 15-mm-diameter cylindrical osteochondral grafts were isolated; two of these grafts (a total of twenty-four grafts in the study) were transplanted with standard impact insertion into recipient sockets in the other condyle of the ipsilateral femur. The other two grafts served as unloaded controls. Loads were measured during the insertion of ten of the twenty-four transplanted grafts. Full-thickness cartilage disks were then removed from the grafts, incubated for up to forty-eight hours, and analyzed for cell viability, TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling)-positive reactivity, and caspase-3 activation, each as a function of the depth from the articular surface., Results: The insertion of an osteochondral graft was characterized, on the average (and standard deviation), by 10 +/- 4 impacts, each generating 2.4 +/- 0.9 kN of load and 13.3 +/- 4.9 MPa of stress for a duration of 0.57 +/- 0.13 ms with a 0.62 +/- 0.25 N.s impulse. Impact insertion increased cell death in the superficial 500 mum to 21% at one hour (p < 0.001) and 47% at forty-eight hours (p < 0.001) and also increased cell death in deeper layers at forty-eight hours. Some cell death was due to apoptosis, as indicated by an increase in caspase-3 activation at eight hours (p < 0.01) and TUNEL-positive cells at forty-eight hours (p < 0.05) in the superficial 500 mum of impacted cartilage., Conclusions: Impact insertion of osteochondral grafts generates damaging loads that cause chondrocyte death, particularly in the superficial zone, mainly as a result of apoptosis mediated by the activation of caspases., Clinical Relevance: Chondrocyte death that occurs during impact insertion of osteochondral grafts may lead to compromised function. Understanding the mechanisms and consequences of such impact loading may provide insights into potential therapeutic interventions, or lead to changes in the insertion technique, to decrease the cell injury associated with impact loading.

Historically, fresh human osteochondral allografts have been stored in lactated Ringer's solution at 4 degrees C and then transplanted as quickly as possible, generally within 2 to 5 days, to ensure delivery of a high level of viable chondrocytes. Recently, allograft distribution companies have begun to provide fresh osteochondral allografts that are stored in a proprietary culture medium usually for at least 2 weeks before delivery to the surgeon for implantation. The effects of such storage on human cartilage have not been well-defined. In the current study the effects of storage in lactated Ringer's solution and in culture media were assessed. After 7 days of storage in lactated Ringer's solution, a significant decline in chondrocyte viability and metabolic activity was seen. Culture media provided significantly better preservation of the cartilage with viability and metabolic activity remaining essentially unchanged from baseline for as many as 14 days. The biochemical and biomechanical properties of the extracellular matrix remained stable with storage in both solutions with time. These data suggest that osteochondral allografts stored under traditional conditions in lactated Ringer's solution should continue to be implanted as quickly as possible and certainly within 7 days of donor death. If kept in culture media, the storage duration may be extended to approximately 2 weeks.

Objective: To determine 1) the kinetics and strength of adhesion of human articular chondrocytes to a cut cartilage surface, and 2) the role of specific integrins in mediating such adhesion, using an in vitro model., Methods: Human articular chondrocytes isolated from cadaveric donors (mean +/- SD age 38 +/- 13 years) were cultured in high-density or low-density monolayer. Following release from culture with trypsin and a 2-2.5-hour recovery period, chondrocytes were analyzed either for adhesion to cartilage or for integrin expression by flow cytometry., Results: Following culture in monolayer, adhesion of chondrocytes to cartilage increased with time, from 6-16% at 10 minutes to a maximum of 59-82% at 80-320 minutes. After 80 minutes of adhesion, the resistance of cells to flow-induced shear stress (50% detachment) was approximately 21 Pa. Chondrocyte adhesion to cartilage decreased with pretreatment of cells with monoclonal antibodies that bound to and blocked certain integrins. After an 80-minute incubation time, adhesion of chondrocytes cultured in high-density monolayer decreased from the value of IgG1-treated controls (55%) with blocking of the beta1 integrin subunit (to 23%) or with blocking of alpha 5 beta 1 (to 36%). Following expansion of chondrocytes in low-density monolayer, the mechanisms of adhesion to cartilage were generally similar. After an 80-minute incubation time, adhesion of chondrocytes cultured in low-density monolayer decreased from the value of IgG1-treated controls (62%) with blocking of the beta1 integrin subunit (to 30%) or with blocking of alpha 5 beta 1 (to 44%). Additionally, adhesion of these cells decreased to 46% by blocking of alpha v beta 5, with a similar trend in effect for chondrocytes cultured in high-density monolayer. Blocking of the alpha 1 or alpha 3 integrin subunits or alpha v beta 3 had no detectable effect on adhesion, even though these receptors were detected by flow cytometry., Conclusion: Under the culture and seeding conditions studied, beta1, alpha 5 beta 1, and alpha v beta 5 integrins mediate human chondrocyte adhesion to cartilage. These chondrocyte integrins have a potential role in the initial adhesion and retention of chondrocytes at a cartilage defect site following clinical procedures of chondrocyte transplantation.

Fresh osteochondral allografts have a long clinical history and have demonstrated use in a wide spectrum of knee joint pathology. The allografting procedure takes advantage of the unique characteristics of osseous and chondral tissue components. Transplanted bone is readily incorporated by the host while the articular cartilage survives transplantation. Allografts have demonstrated >75% clinical success in the treatment of focal femoral condyle lesions due to trauma, chondral injury, osteochondral trauma, osteochondritis dissecans, avascular necrosis, and post-traumatic reconstruction. Fresh allografts also are finding an increasing role in the salvage of difficult cases that have failed other cartilage procedures, and particularly in individuals who are believed to be too young and active for joint arthroplasty. Further refinements in the technical aspects of the allografting procedure, as well as further understanding of the biology of osteochondral allografts, should lead to improved clinical outcomes.

Articular cartilage is susceptible to impact injury. Impact may occur during events ranging from trauma to surgical insertion of an OsteoChondral Graft (OCG) into an OsteoChondral Recipient site (OCR). To evaluate energy density as a mediator of cartilage damage, a specialized drop tower apparatus was used to impact adult bovine samples while measuring contact force, cartilage surface displacement, and OCG advancement. When a single impact was applied to an isolated (non-inserted) OCG, force and surface displacement each rose monotonically and then declined. In each of five sequential impacts of increasing magnitude, applied to insert an OCG into an OCR, force rose rapidly to an initial peak, with minimal OCG advancement, and then to a second prolonged peak, with distinctive oscillations. Energy delivered to cartilage was confirmed to be higher with larger drop height and mass, and found to be lower with an interposed cushion or OCG insertion into an OCR. For both single and multiple impacts, the total energy density delivered to the articular cartilage correlated to damage, quantified as total crack length. The corresponding fracture toughness of the articular cartilage was 12.0 mJ/mm2. Thus, the biomechanics of OCG insertion exhibits distinctive features compared to OCG impact without insertion, with energy delivery to the articular cartilage being a factor highly correlated with damage.

Background: A major limitation of osteochondral allografts (OCA) is the deterioration of cartilage health associated with cell death during prolonged storage. However, little is known about the mechanisms that contribute to chondrocyte death during storage. Purpose/Hypothesis: This study aimed to determine whether bioactive lipid metabolites accumulate in the storage media of OCA and whether they are associated with a loss of chondrocyte viability during prolonged storage. It was hypothesized that free fatty acids (FFAs) would accumulate over time in the storage media of OCA and adversely affect cartilage health during storage. Study Design: Controlled laboratory study. Methods: A group of 21 (n = 6-8 OCA/treatment group) fresh human hemicondylar OCA tissues and media were analyzed after 7, 28, and 68 days of prolonged cold (4°C) storage. Targeted mass spectrometry analysis was used to quantify bioactive FFAs, as well as primary (lipid hydroperoxide [ROOH]) and secondary (malondialdehyde) lipid oxidation products. Chondrocyte viability was measured using a fluorescence-based live/dead assay and confocal microscopy. Results: The concentration of all targeted fatty acid metabolites in storage media was significantly increased with increased cold storage time (P <.05). ROOH was significantly higher on day 28 of cold storage. No difference in secondary ROOH products in storage media was observed. Chondrocyte viability significantly declined in both the en face and the vertical cross-sectional analysis with increased cold storage time and inversely correlated with fatty acid metabolites (P <.05). Conclusion: It is well established that elevated levels of certain FFAs and lipid oxidation products can alter cell function and cause cell death via lipotoxicity and other mechanisms. This work is the first to identify elevated levels of FFA metabolites and primary oxidation lipid products in the storage media from clinical OCA. The concentrations of FFA metabolites were measured at levels (>100 µM) known to induce cell death and were directly correlated with chondrocyte viability. Clinical Relevance: These findings provide important targets for understanding why cartilage health declines during cold storage, which can be used to optimize media formulations and improve graft health. [ABSTRACT FROM AUTHOR]

BackgroundOsteochondral allograft (OCA) transplantation is an effective treatment for defects in the medial femoral condyle (MFC), but the procedure is limited by a shortage of grafts. Lateral femoral condyles (LFCs) differ in geometry from MFCs but may be a suitable graft source. The difference between articular surface locations of the knee can be evaluated with micro-computed tomography imaging and 3-dimensional image analysis.HypothesisLFC OCAs inserted into MFC lesions can provide a cartilage surface match comparable with those provided by MFC allografts.Study designControlled laboratory study.MethodsTwenty MFCs and 10 LFCs were divided into 3 groups: 10 MFC recipients (MFCr), 10 MFC donors (MFCd), and 10 LFC donors (LFCd). A 20-mm defect was created in the weightbearing portion of the MFCr. Two grafts, 1 MFCd and 1 LFCd, were implanted sequentially into each MFCr. Micro-computed tomography (μCT) images of the MFCr were acquired and analyzed to compare the topography of the original recipient site with the MFCd- and LFCd-repaired sites. Three-dimensional transformations were defined to register the defect site in the 3 scans of each MFCr. Vertical deviations from each voxel of the graft cartilage surface, relative to the intact recipient cartilage surface, were calculated and assessed as root mean square deviation and percentage graft area that was proud, sunk, and within the "acceptable" distance (±1.00 mm). The effect of repair (with MFC vs with LFC) on each of the surface match parameters is presented as mean ± SD and was assessed by t test: height deviation over area (root mean square, mm), graft area acceptable (%), area unacceptably proud (%), area unacceptably sunk (%), step-off height over circumference (root mean square, mm), graft circumference acceptable (%), circumference unacceptably proud (%), and circumference unacceptably sunk (%). Percentage data were arcsin transformed before statistical testing. An alpha level of 0.05 was used to conclude if variations were statistically significant.ResultsMFCr defects were filled with both orthotopic MFCd and nonorthotopic LFCd. Registered μCT images of the MFCr illustrate the cartilage surface contour in the sagittal and coronal planes, in the original intact condyle, as well as after OCA repairs. Specimen-specific surface color maps for the MFCr after implant of the MFCd and after implant of LFCd were generally similar, with some deviation near the edges. On average, the MFCr site exhibited a typical contour, and the MFCd and LFCd were slightly elevated. Both types of OCA-MFCd and LFCd-matched well, showing overall height deviations of 0.63 mm for area and 0.47 mm for step-off, with no significant difference between MFCd and LFCd (P = .92 and .57, respectively) and acceptable deviation based on area (87.6% overall) and step-off (96.7% overall), with no significant difference between MFCd and LFCd (P = .87 and .22, respectively). A small portion of the implant was proud (12.1% of area and 2.6% of circumference step-off height), with no significant difference between MFCd and LFCd (P = .26 and .27, respectively). A very small portion of the implant area and edge was sunk (0.3% of area and 0.6% of circumference), with no significant difference between MFCd and LFCd (P = .29 and .86, respectively).Conclusion/clinical relevanceThe achievement of excellent OCA surface match with an MFCd or LFCd graft into the common MFCr site suggests that nonorthotopic LFC OCAs are acceptable graft options for MFC defects.

Background: Focal cartilage defects are often debilitating, possess limited potential for regeneration, are associated with increased risk of osteoarthritis, and are predictive for total knee arthroplasty. Cartilage repair studies typically focus on the outcome in younger patients, but a high proportion of treated patients are 40 to 60 years of age (ie, middle-aged). The reality of current clinical practice is that the ideal patient for cartilage repair is not the typical patient. Specific attention to cartilage repair outcomes in middle-aged patients is warranted. Purpose: To systematically review available literature on knee cartilage repair in middle-aged patients and include studies comparing results across different age groups. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic search was performed in EMBASE, MEDLINE, and the Cochrane Library database. Articles were screened for relevance and appraised for quality. Results: A total of 21 articles (mean Coleman Methodology Score, 64 points) were included. Two out of 3 bone marrow stimulation (BMS) studies, including 1 using the microfracture technique, revealed inferior clinical outcomes in middle-aged patients in comparison with younger patients. Nine cell-based studies were included showing inconsistent comparisons of results across age groups for autologous chondrocyte implantation (ACI). Bone marrow aspirate concentrate showed age-independent results at up to 8 years of follow-up. A negative effect of middle age was reported in 1 study for both ACI and BMS. Four out of 5 studies on bone-based resurfacing therapies (allografting and focal knee resurfacing implants [FKRIs]) showed age-independent results up to 5 years. One study in only middle-aged patients reported better clinical outcomes for FKRIs when compared with biological repairs. Conclusion: Included studies were heterogeneous and had low methodological quality. BMS in middle-aged patients seems to only result in short-term improvements. More research is warranted to elucidate the ameliorating effects of cell-based therapies on the aging joint homeostasis. Bone-based therapies seem to be relatively insensitive to aging and may potentially result in effective joint preservation. Age subanalyses in cohort studies, randomized clinical trials, and international registries should generate more evidence for the large but underrepresented (in terms of cartilage repair) middle-aged population in the literature. [ABSTRACT FROM AUTHOR]

The technique of osteochondral allograft (OCA) transplantation has been used to treat a wide spectrum of cartilage deficiencies in the knee. Its use has been supported by basic science and clinical studies that show it is a safe and effective treatment option. What sets fresh OCA transplantation apart from other cartilage procedures in the knee, is the ability to treat large defects with mature hyaline cartilage. Studies looking at transplantation of fresh OCAs in the general population have shown reliable pain relief and return to activities of daily living. Reports of cartilage injuries in athletes have risen over the years and more research is needed in evaluating the successfulness of OCA transplantation in the athletic population. [ABSTRACT FROM AUTHOR]

Background: Osteochondral allografts are an increasingly popular treatment for the repair of articular cartilage lesions. Current tissue bank protocols require bacteriological testing that takes from 21 to 28 days to process. During this time, tumor necrosis factor–alpha (TNF-α, a proapoptotic cytokine) is upregulated, resulting in loss of chondrocyte viability. To date, etanercept (a cytokine inhibitor) has not been studied in the current storage paradigm with the intention of preserving cell viability.Purpose: This study was undertaken to assess whether the addition of etanercept can improve the chondrocyte viability ofosteochondral allograft during storage.Study Design: Controlled laboratory study.Methods: Osteochondral allografts were harvested from 8 Boer goat femurs and placed into storage media and stored at 4°C for 28 days. The experimental group was supplemented with 10 µg/mL of etanercept. After storage, cell viability was assessed by live/dead staining and confocal microscopy. Specimens were also analyzed histologically and underwent histomorphologic analysis. TNF-α expression was measured with semiquantitative polymerase chain reaction.Results: At 28 days, the percentage viability of the superficial zone in etanercept-treated allografts was maintained at significantly higher levels than those measured in the untreated group (69.3 ± 9.4 compared with 47.8 ± 19.1, P = .01). No difference was found histologically between the etanercept and the untreated group (ie, safranin O staining for glycosaminoglycan expression). Histomorphologic assessment showed no difference in indentation stiffness or roughness between groups. TNF-α expression was significantly decreased in the etanercept group compared to the untreated group.Conclusion: Etanercept was able to maintain cell viability of osteochondral allografts significantly better than the current storage paradigm after 28 days of storage.Clinical Relevance: Maintaining the viability of the superficial zone will benefit outcomes by facilitating joint articulation via improved lubrication. Additionally, maintaining the cellular viability for increased periods of time may allow a greater window of time in which a suitable recipient may be found. [ABSTRACT FROM AUTHOR]

Background: Fresh human osteochondral allografting is a biological cartilage replacement technique used to treat articular and osteoarticular defects in the knee. A small number of grafts fail, and we analyzed every retrieved graft during a 4-year period in order to learn more about the potential causes of failure. Hypothesis: A large percentage of chondrocytes still remain viable many years after fresh osteochondral allografting. Study Design: Descriptive laboratory study. Methods: Retrieval specimens were obtained at the time of revision surgery and immediately analyzed. Chondrocyte viability and viable cell density were determined using a live/dead staining technique followed by confocal microscopy. Glycosaminoglycan content was a measure of the cartilage matrix. Radiolabeled sulfate uptake served as a biochemical marker of chondrocyte metabolic activity. Cartilage and subchondral bone were examined histologically. Results: Fourteen patients yielded a total of 26 retrieval specimens that had been originally implanted as individual fresh osteochondral allografts. Average graft survival was 42 months. Chondrocyte viability was 82% ± 17%, and chondrocyte viable cell density was 15 590 ± 5900 viable cells/mm3. Retrieved tissue demonstrated radiolabeled sulfate uptake of 437 ± 270 counts per minute and 3.5% ± 0.8% hexosamine per dry weight. Histologically, all specimens showed some degree of cartilage fibrillation. There was evidence of bone allograft incorporation in most specimens, as well as pannus formation in 4 specimens, but no evidence of immune rejection. Conclusion: A small percentage of fresh osteochondral allografts fail, but the precise cause is unknown. The main theories for failure investigated here include immunologic rejection, failure of bony incorporation, and chondrocyte death causing breakdown of the cartilage matrix. We show that chondrocytes remain viable many years after transplantation, allograft bone incorporates, and immune rejection does not seem to play a primary role in failure. Clinical Relevance: Fresh osteochondral allografting is becoming more common in the treatment of articular cartilage defects in the knee. Our findings support the paradigm of fresh osteochondral allografting, the transplantation of hyaline cartilage with biological incorporation of the underlying bone scaffold. The reasons for failure of a small percentage of grafts remain unclear. [ABSTRACT FROM AUTHOR]

Background: The treatment of osteochondritis dissecans in the adult knee can be challenging. As part of our comprehensive treatment program, fresh osteochondral allografts have been used in the surgical management of osteochondritis dissecans of the femoral condyle. Hypothesis: Fresh osteochondral allograft transplantation will provide a successful surgical treatment for osteochondritis dissecans of the femoral condyle. Study Design: Case series; Level of evidence, 4. Methods: Sixty-six knees in 64 patients underwent fresh osteochondral allografting for the treatment of osteochondritis dissecans. Each patient was evaluated both preoperatively and postoperatively using an 18-point modified D'Aubigné and Postel scale. Subjective assessment was performed using a patient questionnaire. Radiographs were evaluated preoperatively and postoperatively. Results: Mean follow-up was 7.7 years (range, 2–22 years). There were 45 men and 19 women with a mean age of 28.6 years (range, 15–54 years). All patients had undergone previous surgery. Forty-one lesions involved the medial femoral condyle, and 25 involved the lateral femoral condyle. All were osteochondritis dissecans type 3 or 4. The mean allograft size was 7.5 cm². One knee was lost to follow-up. Of the remaining 65 knees, 47 (72%) were rated good/excellent, 7 (11%) were rated fair, and 1 (2%) was rated poor. Ten patients (15%) underwent reoperation. The mean clinical score improved from 13.0 preoperatively to 16.4 postoperatively (P < .01). Fifty-nine of 64 patients completed questionnaires. Subjective knee function improved from a mean of 3.4 to 8.4 on a 10-point scale (P < .01). Conclusion: With greater than 70% good or excellent results, fresh osteochondral allograft transplantation is a successful surgical treatment for osteochondritis dissecans of the femoral condyle. [ABSTRACT FROM AUTHOR]

Background: Osteochondral allografts are currently stored at 4°C for 2 to 6 weeks before implantation. At 4°C, chondrocyte viability, especially in the superficial zone, deteriorates starting at 2 weeks. Alternative storage conditions could maintain chondrocyte viability beyond 2 weeks, and thereby facilitate increased graft availability and enhanced graft quality.Purpose: The objective of the study was to determine the effects of prolonged 37°C storage compared with traditional 4°C storage on chondrocyte viability and cartilage matrix content.Study Design: Controlled laboratory study.Methods: Osteochondral samples from humeral heads of adult goats were analyzed (i) fresh, or after storage in medium for (ii) 14 days at 4°C including 10% fetal bovine serum, (iii) 28 days at 4°C including 10% fetal bovine serum, (iv) 28 days at 37°C without fetal bovine serum, (v) 28 days at 37°C including 2% fetal bovine serum, or (vi) 28 days at 37°C including 10% fetal bovine serum. Portions of samples were analyzed by microscopy after LIVE/DEAD staining to determine chondrocyte viability and density, both en face (to visualize the articular surface) and vertically (overall and in superficial, middle, and deep zones). The remaining cartilage was analyzed for sulfated glycosaminoglycan and collagen.Results: The 37°C storage maintained high chondrocyte viability compared with 4°C storage. Viability of samples after 28 days at 37°C was ˜80% at the cartilage surface en face, ˜65% in the superficial zone, and ˜70% in the middle zone, which was much higher than ˜45%, ˜20%, and ˜35%, respectively, in 4°C samples after 28 days, and slightly decreased from ˜100%, ˜85%, and ˜95%, respectively, in fresh controls. Cartilage thickness, glycosaminoglycan content, and collagen content were maintained for 37°C and 4°C samples compared with fresh controls.Conclusion: The 37°C storage of osteochondral grafts supports long-term chondrocyte viability, especially at the vulnerable surface and superficial zone of cartilage.Clinical Relevance: Storage of allografts at a physiologic temperature of 37°C may prolong storage duration, improve graft availability, and improve treatment outcomes. [ABSTRACT FROM PUBLISHER]