Engineering Tissues That Mimic the Zonal Nature of Articular Cartilage Using Decellularized Cartilage Explants Seeded with Adult Stem Cells.

Abstract

Articular cartilage (AC) possesses uniquely complex mechanical properties; for example its stiffness increases with depth through the tissue and it softens when compressed. These properties are integral to the function of AC and can be attributed to the tissue's collagen network and how it interacts with negatively charged proteoglycans. In this study, scaffolds containing arrays of channels were produced from decellularized AC explants derived from skeletally immature and mature pigs. These scaffolds were then repopulated with human infrapatellar fat pad derived stem cells (FPSCs). After 4 weeks in culture, FPSCs filled channels within the decellularized explants with a matrix rich in proteoglycans and collagen. Cellular and neo-matrix alignment within these scaffolds appeared to be influenced by the underlying collagen architecture of the decellularized cartilage. Repopulating scaffolds derived from decellularized skeletally mature cartilage with FPSCs led to the development of engineered cartilage with depth-dependent mechanical properties mimicking aspects of native tissue. Furthermore, these constructs displayed the characteristic strain softening behavior of AC. These findings highlight the importance of the collagen network to engineering mechanically functional cartilage grafts.