Developmentally Inspired Approach to Cartilage Tissue Engineering

Abstract

Structural organization of articular cartilage is rooted in the arrangement of mesenchymal stem cells (MSCs) into morphologically distinct zones during embryogenesis as a result of spatiotemporal gradients in biochemical, mechanical, and cellular factors that direct the formation of stratified structure of articular cartilage. These gradients are central to the function of cartilage as an articulating surface. Strategies that mimic zonal organization of articular cartilage are more likely to create an engineered tissue with more effective clinical outcome. The objective of this work was to measure the expression of human MSCs encapsulated in engineered gels that simulate stiffness of the superficial, middle and calcified zones of articular cartilage supplemented with zone specific growth factors. Size of the encapsulated cells increased from the gel simulating superficial zone to those simulating middle and calcified zones. Glycosaminoglycans (GAG) content progressively increased from the gel simulating superficial zone to those simulating middle and calcified zones. Human MSCs in the gel simulating the superficial zone showed up-regulation of Sox-9 and SZP whereas those in the calcified gel showed up-regulation of ALP. Results demonstrate that a developmental approach can potentially regenerate the zonal structure of articular cartilage.