Size dependent regeneration capacity of functionalized Capra ear-derived micro-tissue scaffolds for treatment of cartilage defects

Abstract

Regeneration of cartilage still possesses considerable challenge in orthopedic treatment owing to avascular nature and lack of self-healing ability of the tissue. In this context, cartilage defect recovery via engineered functional micro tissue delivery is an emerging trend in musculoskeletal therapeutics. This work explores the efficacy of Capra ear-derived functionalized micro-tissues (FMTs) for regeneration of cartilage defects. For this study, a novel and inexpensive NaOH-based decellularization method was developed and optimized to obtain complete removal of cells without deteriorating the matrix structure of Capra ear cartilage. The decellularized matrix was then processed to generate micro-scaffolds (MSs) with different size distributions. It was established that among those size groups, MSs having 100 µm average size were most effective for adherence, cell proliferation and differentiation. It was assessed that the loose fibrous structure of smaller scaffolds was able to induce chondrogenic differentiation. Further, a frugal system was devised for performing hanging culture on the MSs with adipose tissue derived mesenchymal stem cells (ADMSCs) to generate functionalized micro tissues (FMTs). Finally, FMTs were implanted in rabbit auricular cartilage defects to evaluate their healing efficacy. Histology, FTIR and microCT studies revealed that the implanted FMTs were able to regenerate the defect within 60 days. Thus, this work establishes that the functionalized micro tissues derived from decellularized capra ear cartilage can potentially be used for cartilage regeneration, and the efficacy of regeneration depends on the size along with the fibrous structure of the scaffolds.