This study examines the effects of the addition of a scaffold to enhance cartilage healing during microfracture for the treatment of an isolated articular cartilage defect in the knee. The authors are to be commended on their excellent study design and multicenter (twenty-six international clinical sites), prospective, randomized, single-blinded, Level-I trial comparing microfracture alone with microfracture augmented with BST-CarGel scaffold.
BST-CarGel scaffold is hypothesized to stabilize the marrow-derived blood clot following penetration of the subchondral bone. Additionally, BST-CarGel is thought to reinforce clot formation by increasing adhesiveness and to prevent platelet-derived retraction. The authors hypothesized that microfracture augmented with BST-CarGel would result in improved cartilage repair with regards to defect fill, quantity, quality, and clinical outcomes as compared with microfracture alone. This study found significantly better defect percent fill (92.8% versus 85.2%; p = 0.011) and increased hyaline cartilage-like magnetic resonance imaging (MRI) findings (p = 0.033) at the time of the latest follow-up. There were no differences with regard to clinical outcome for the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Short Form-36 (SF-36) scores at twelve months. Subgroup analysis of male patients less than thirty-five years of age with a high activity level demonstrated significantly greater improvement as compared with microfracture with regard to pain (44%; p = 0.02) and function (56%; p = 0.02) on the WOMAC subscale scores.
The study design was well thought out with a strong randomization technique and adequate power based on a priori power analysis. Additionally, validated outcomes measures were used (WOMAC and SF-36) to assess clinical results. Attempts to reduce bias were made throughout the study via single-blinded evaluation of MRI to assess cartilage percent fill and quality. Selection and performance bias was reduced with the international multicenter study design. The biggest flaw is the reporting of relatively short follow-up (one year) and not reporting longer-term follow-up on these patients. This short follow-up did not allow assessment of articular cartilage repair site longevity or clinical correlation with durability and clinical outcome.
There are currently limited data in the literature on the outcomes of scaffold-augmented microfracture or autologous matrix-induced chondrogenesis for the treatment of isolated articular cartilage lesions. The use of several different augments has been reported, including platelet-rich plasma gel, collagen patch, polyglycolic acid patch treated with hyaluronic acid, and porcine collagen matrix, and results have been limited to case reports and case series1. The goals of these procedures are to replicate the benefits from autologous chondrocyte transplantation by promoting the migration of mesenchymal stem cells from the subchondral bone and to provide a protective scaffold to stabilize the blood clot in place, allowing for improved cartilage repair quality and quantity.
In a Level-IV study, Dhollander et al.2 reported the outcome in a small case series of five patients managed with microfracture augmented with a cell-free polymer-based matrix and found improvement in clinical outcomes scores (Knee Injury and Osteoarthritis Outcome Score[KOOS], Tegner, visual analog scale [VAS]) as well as MRI evaluation of cartilage quality and defect percent fill, with three of their five patients demonstrating complete or hypertrophic defect fill at the twenty-four-month follow-up. In a Level-IV study, Kusano et al.3 retrospectively reviewed the results of autologous matrix-induced chondrogenesis in thirty-eight patients and found significant improvements in clinical outcomes scores (International Knee Documentation Committee [IKDC], Lysholm, Tegner, and VAS), but inconsistent radiographic defect percent fill ranging from 18% having complete fill to 38% having <50% fill. Of note, only a subset (sixteen of thirty-six) of subjects underwent MRI evaluation because of metal implants limiting the validity of these results. In a Level-IV study, Siclari et al.4 retrospectively reviewed the results of fifty-two subjects who underwent microfracture enhanced with a polyglycolic acid-hyaluronan scaffold immersed with platelet-rich plasma. The authors found statistically and clinically significant improvements in KOOS pain (36 points; p < 0.001), symptoms (31 points; p < 0.001), activities of daily living (17 points; p < 0.001), sports and recreation function (34 points; p < 0.001), and knee-related quality of life (35 points; p < 0.001) subscales at the twelve-month follow-up. In addition, five subjects underwent biopsy and had hyaline-like cartilage tissue based on immunohistochemistry.
To my knowledge, this is the first prospective, randomized, multicenter Level-I study comparing microfracture with a one-stage autologous matrix-induced chondrogenesis technique.
The authors of the current study proposed that microfracture augmented with BST-CarGel resulted in greater lesion filling than microfracture alone and that this structural improvement may be predictive of long-term durability and sustained clinical outcome. Although this is a reasonable theory, on the basis of the results of this study, there are not enough data to support this hypothesis. Following the outcomes of these subjects for five to ten years may provide the evidence that is needed for these results to impact clinical practice. It would be of interest to learn how the percentage of defect fill and its correlation with the WOMAC score (or other validated outcomes scores) change over time. That being said, with the current state of health-care reform and cost containment, this technique may provide a reasonable alternative to the more expensive two-stage autologous chondrocyte implantation or matrix-assisted chondrocyte transplantation procedures. Future well-designed, prospective, randomized multicenter trials would be helpful to develop an evidence-based approach to guide treatment.