Standard microfracture is a first-line, widely used and cost-effective surgical technique for repairing damaged articular cartilage, but, it is limited by decreased long-term efficacy and limited applicability in larger lesions. This leads to a burgeoning economic burden associated with primary and follow-up treatment costs, estimated at more than 40 billion dollars annually in the U.S. alone. It follows that any therapy that improves surgical outcomes for cartilage defects and reduces overall treatment costs will have significant clinical and economical impact. Therefore, the overall goal of this study is to evaluat an implantable, cell-free reinforcing and chondroinductive scaffold for enhancing repair of large, full-thickness cartilage lesions in a large animal model (ovine) treated with standard microfracture. This scaffold is based on a three-dimensional (3D) woven fiber scaffold made from poly(caprolactone) that we have previously demonstrated to promote and support the synthesis of a robust cartilaginous extracellular matrix rich in proteoglycans and type II collagen all while maintaining appropriate biomimetic mechanical properties, largely owing to the slow degradation of PCL (~5% after 2 years). We have also demonstrated the ability of this cell-free implant to remain in a critically-sized defect without the need for additional anchoring. In this study, 24 adult sheep will receive, large (~80mm2), unilateral chondral defects on right medial femoral condyles. In 12 sheep, defects will be treated with standard microfracture and then covered with custom-fit 3D-woven PCL implants. The remaining 12 sheep will be treated with standard microfracture only. Sheep will be sacrificed at 12 (n=6 for each group) or 24 (n=6 for each group) weeks post-procedure. All operated joints will be radiographed immediately postoperatively, at 1 week, 2 weeks, 6 weeks, and 12 weeks in the live animals, and at the 12 and 24-week sacrifice dates. Following necropsy joints will be evaluated by CT and gross and histological semi- quantitative scoring. In addition, mechanical properties of repair tissue, the surrounding cartilage, and native cartilage from contralateral limb condyles will be analyzed via indentation testing. Data are expected to be instructive in determining if our product is able to enhance cartilage regeneration in a large osteochondral defect in terms of its gross and histological appearance as well as mechanical properties in relation to native hyaline cartilage. We have significant preliminary data to support our taking this logical next step toward evaluating the commercial potential of this approach, and we believe this study will enable us to assess the efficacy of our technology for enhancing repair and increasing the patient population for microfracture surgery, towards the goal of delaying or eliminating the need for follow-up procedures.
Standard microfracture is a first-line, widely used and cost-effective surgical technique for repairing damaged articular cartilage, but is limited by decreased long-term efficacy and limited applicability in larger lesions. We will evaluate the use of an advanced three-dimensional weaving technology to produce a cell-free, reinforcing and chondroinductive implant for improving the quality and longevity of repaired focal cartilage defects in a sheep model following standard microfracture. Successful outcomes would move this technology closer to a clinical reality, potentially broadening the applicability of microfracure to patients with larger lesions that currently show limited repair.