Chondral and osteochondral lesions due to injury or other pathology commonly result in the development of osteoarthritis, eventually leading to progressive total joint destruction. Although current progress suggests that biologic agents can delay the advancement of deterioration, such drugs are incapable of promoting tissue restoration. The limited ability of articular cartilage to regenerate renders joint arthroplasty an unavoidable surgical intervention. This Review describes current, widely used clinical repair techniques for resurfacing articular cartilage defects; short-term and long-term clinical outcomes of these techniques are discussed. Also reviewed is a developmental pipeline of acellular and cellular regenerative products and techniques that could revolutionize joint care over the next decade by promoting the development of functional articular cartilage. Acellular products typically consist of collagen or hyaluronic-acid-based materials, whereas cellular techniques use either primary cells or stem cells, with or without scaffolds. Central to these efforts is the prominent role that tissue engineering has in translating biological technology into clinical products; therefore, concomitant regulatory processes are also discussed.

https://escholarship.org/content/qt76m4g3q5/qt76m4g3q5.pdf?t=oe66jy

Repair and tissue engineering techniques for articular cartilage

Background Despite the popularity of microfracture as a first-line treatment for articular cartilage defects in the knee, systematic information on its clinical efficacy for articular cartilage repair and long-term improvement of knee function is not available. Hypothesis Systematic analysis of the existing clinical literature of microfracture in the knee can improve the understanding of the advantages and limitations of this cartilage repair technique and can help to optimize its indications and clinical outcomes. Study design Systematic review. Methods A comprehensive literature search was performed using established search engines (MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials) to identify original human studies of articular cartilage repair with microfracture. Modified Coleman Methodology Scores were used to analyze the quality of the existing studies. Clinical efficacy of articular cartilage repair was evaluated by systematic analysis of short- and long-term functional outcome scores, macroscopic and microscopic repair cartilage quality, and findings of postoperative magnetic resonance imaging. Results Twenty-eight studies describing 3122 patients were included in the review. The average follow-up was 41 months, with only 5 studies reporting follow-up of 5 years or more. Six studies were randomized controlled trials and the mean Coleman Methodology Score was 58 (range, 22-97). Microfracture effectively improved knee function in all studies during the first 24 months after microfracture, but the reports on durability of the initial functional improvement were conflicting. Several factors were identified that affected clinical outcome. Defect fill on magnetic resonance imaging was highly variable and correlated with functional outcome. Macroscopic repair cartilage quality positively affected long-term failure rate, while the influence of histologic repair tissue quality remained inconclusive. Conclusion This systematic analysis shows that microfracture provides effective short-term functional improvement of knee function but insufficient data are available on its long-term results. Shortcomings of the technique include limited hyaline repair tissue, variable repair cartilage volume, and possible functional deterioration. The quality of the currently available data on micro-fracture is still limited by the variability of results and study designs. Further well-designed studies are needed to determine the long-term efficacy of microfracture and to define its specific clinical indications compared to other cartilage repair techniques.

Clinical Efficacy of the Microfracture Technique for Articular Cartilage Repair in the Knee An Evidence-Based Systematic Analysis

Background: Damaged articular cartilage has limited capacity for self-repair. Autologous chondrocyte implantation using a characterized cell therapy product results in significantly better early structural repair as compared with microfracture in patients with symptomatic joint surface defects of the femoral condyles of the knee.Purpose: To evaluate clinical outcome at 36 months after characterized chondrocyte implantation (CCI) versus microfracture (MF).Study Design: Randomized controlled trial; Level of evidence, 1.Methods: Patients aged 18 to 50 years with single International Cartilage Repair Society (ICRS) grade III/IV symptomatic cartilage defects of the femoral condyles were randomized to CCI (n = 57) or MF (n = 61). Clinical outcome was measured over 36 months by the Knee injury and Osteoarthritis Outcome Score (KOOS). Serial magnetic resonance imaging (MRI) scans were scored using the Magnetic resonance Observation of Cartilage Repair Tissue (MOCART) system and 9 additional items. Gene expression...

Treatment of Symptomatic Cartilage Defects of the Knee Characterized Chondrocyte Implantation Results in Better Clinical Outcome at 36 Months in a Randomized Trial Compared to Microfracture

This chapter provides criteria for evaluating permanent impairment of the visual system as it affects an individual’s ability to perform activities of daily living. The visual system consists of the eyes and supporting structures, the neural pathways, and the visual cortex of the brain. The visual system is unique in that it combines the input from two separate eyes into a single visual perception.

Guides to the Evaluation of Permanent Impairment

MSC exosome as a cell-free MSC therapy for cartilage regeneration: Implications for osteoarthritis treatment.

BackgroundAutologous chondrocyte implantation (ACI) has become an accepted option for the treatment of chondral defects in carefully selected patients. Current recommendations limit this procedure to younger patients, as insufficient data are available to conclusively evaluate outcomes in patients older than 45 years.HypothesisCartilage repair with ACI in patients older than 45 years results in substantially different outcomes than those previously reported for younger age groups.Study DesignCase series; Level of evidence, 4.MethodsThis prospective cohort study reviewed patients 45 years of age at the time of treatment with ACI. The clinical evaluation included a patient satisfaction questionnaire and four validated rating scales: Short Form-36, Modified Cincinnati Rating Scale, WOMAC (Western Ontario and McMaster Universities) Osteoarthritis Index, and the Knee Society Score.ResultsA total of 56 patients 45 years of age were treated with ACI. The average patient age at index surgery was 48.6 years (ran...

Repair of Large Chondral Defects of the Knee With Autologous Chondrocyte Implantation in Patients 45 Years or Older

Young patients with early osteoarthritis wishing to remain functionally active have limited treatment options. Existing studies examining the use of autologous chondrocyte implantation (ACI) have included patients with early degenerative changes; however, none specifically investigated the outcome of ACI with this challenging problem. We prospectively followed 153 patients (155 knees) for up to 11 years after treatment with ACI for early-stage osteoarthritis. Patient pain and function was assessed using WOMAC, modified Cincinnati, SF-36, Knee Society score, and a satisfaction questionnaire. Mean patient age was 38.3 years. On average, 2.1 defects were treated per knee; the mean defect size was 4.9 cm2 and total area per knee was 10.4 cm2. Eight percent of joints were considered treatment failures that went on to arthroplasty and the remaining patients experienced 50% to 75% improvement in WOMAC subscales. Our data suggest that ACI in patients with early osteoarthritis results in clinically relevant reductions in pain and improvement in function. At 5 years postoperatively, 92% of patients were functioning well and were able to delay the need for joint replacement. Given the limited number of treatment options for this subset of patients, autologous chondrocyte implantation may offer improved quality of life for young osteoarthritic patients.

/pdf/autologous-chondrocyte-implantation-for-joint-preservation-wbb7pfahqe.pdf

Autologous Chondrocyte Implantation for Joint Preservation in Patients with Early Osteoarthritis

BackgroundMarrow stimulation techniques such as drilling or microfracture are first-line treatment options for symptomatic cartilage defects. Common knowledge holds that these treatments do not compromise subsequent cartilage repair procedures with autologous chondrocyte implantation.HypothesisCartilage defects pretreated with marrow stimulation techniques will have an increased failure rate.Study DesignCohort study; Level of evidence, 2.MethodsThe first 321 consecutive patients treated at one institution with autologous chondrocyte implantation for full-thickness cartilage defects that reached more than 2 years of follow-up were evaluated by prospectively collected data. Patients were grouped based on whether they had undergone prior treatment with a marrow stimulation technique. Outcomes were classified as complete failure if more than 25% of a grafted defect area had to be removed in later procedures because of persistent symptoms.ResultsThere were 522 defects in 321 patients (325 joints) treated with ...

Increased Failure Rate of Autologous Chondrocyte Implantation After Previous Treatment With Marrow Stimulation Techniques

Hypothesis Cartilage defects pretreated with marrow stimulation techniques will have an increased failure rate. The first 321 consecutive patients treated at one institution with autologous chondrocyte implantation for full-thickness cartilage defects that reached more than two years of follow-up were evaluated by prospectively collected data. Patients were grouped based on whether they had undergone prior treatment with a marrow stimulation technique. Outcomes were classified as complete failure if more than 25% of a grafted defect area had to be removed in later procedures because of persistent symptoms. Results There were 522 defects in 321 patients (325 joints) treated with autologous chondrocyte implantation. On average, there were 1.7 lesions per patient. Of these joints, 111 had previously undergone surgery that penetrated the subchondral bone; 214 joints had no prior treatment that affected the subchondral bone and served as controls. Within the marrow stimulation group, there were 29 (26%) failures, compared with 17 (8%) failures in the control group. Conclusion Defects that had prior treatment affecting the subchondral bone failed at a rate three times that of nontreated defects. The failure rates for drilling (28%), abrasion arthroplasty (27%), and microfracture (20%) were not significantly different—possibly because of the lower number of microfracture patients in this cohort (25 of 110 marrow-stimulation procedures). The data demonstrate that marrow stimulation techniques have a strong negative effect on subsequent cartilage repair with autologous chondrocyte implantation and, therefore, should be used judiciously in larger cartilage defects that could require future treatment with autologous chondrocyte implantation. Unlike coventional wisdom, MSTs do ‘burn bridges’.

Increased failure rate of autologous chondrocyte implantation after previous treatment with marrow stimulation techniques

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Repair of Large Chondral Defects of the Knee With Autologous Chondrocyte Implantation in Patients 45 Years or Older

Autologous Chondrocyte Implantation for Joint Preservation in Patients with Early Osteoarthritis

Increased Failure Rate of Autologous Chondrocyte Implantation After Previous Treatment With Marrow Stimulation Techniques

Increased failure rate of autologous chondrocyte implantation after previous treatment with marrow stimulation techniques