Differential Chondrogenic Potential of Human and Bovine Mesenchymal Stem Cells in Agarose and Photocrosslinked Hyaluronic Acid Hydrogels

Abstract

Articular cartilage has a limited regenerative capacity, and there exist no methodologies to restore structure and function after damage or degeneration. This has focused intense work on cell-based therapies for cartilage repair, with considerable literature demonstrating that chondrocytes in vitro and in vivo can generate cartilage-like tissue replacements. However, use of primary cells is limited by the amount and quality of autologous donor cells and tissue. Multipotential mesenchymal stem cells (MSCs) derived from bone marrow offer an alternative cell source for cartilage tissue engineering. MSCs are easily accessible and expandable in culture, and differentiate towards a chondrocyte-like phenotype with exposure to TGF-β [1]. For example, we have shown that bovine MSCs undergo chondrogenic differentiation and mechanical maturation in agarose, self-assembling peptide, and photocrosslinkable hyaluronic acid (HA) hydrogels [2]. HA hydrogels are particularly advantageous as they are biologically relevant and easily modified to generate a range of hydrogel properties [3]. Indeed, bovine MSCs show a strong dependence of functional outcomes on the macromer density of the HA gel [4]. To further the clinical application of this material, the purpose of this study was to investigate functional chondrogenesis of human MSCs in HA compared to agarose hydrogels. To carry out this study, juvenile bovine and human MSCs were encapsulated and cultured in vitro in HA and agarose hydrogels, and cell viability, biochemical, biomechanical, and histological properties were evaluated over 4 weeks of culture.