The Challenge of Cartilage Integration: Understanding a Major Barrier to Chondral Repair

Articular cartilage defects caused by injury frequently lead to osteoarthritis, a painful and costly disease. Despite widely used surgical methods to treat articular cartilage defects and a plethora of research into regenerative strategies as treatments, long-term clinical outcomes are not satisfactory. Failure to integrate repair tissue with native cartilage is a recurring issue in surgical and tissue-engineered strategies, seeing eventual degradation of the regenerated or surrounding tissue. This review delves into the current understanding of why continuous and robust integration with native cartilage is so difficult to achieve. Both the intrinsic limitations of chondrocytes to remodel injured cartilage, and the significant challenges posed by a compromised biomechanical environment are described. Recent scaffold and cell-based techniques to repair cartilage are also discussed, and limitations of existing methods to evaluate integrative repair. In particular, the importance of evaluating the mechanical integrity of the interface between native and repair tissue is highlighted as a meaningful assessment of any strategy to repair this load-bearing tissue. The failure to integrate grafts or biomaterials with native cartilage is a major barrier to cartilage repair. An in-depth understanding of the reasons cartilage integration remains a challenge is required to inform cartilage repair strategies. In particular, this review highlights that integration of cartilage repair strategies is frequently assessed in terms of the continuity of tissue, but not the mechanical integrity. Given the load-bearing nature of cartilage, evaluating integration in terms of interfacial strength is essential to assessing the potential success of cartilage repair methods.