Gradient Mineralized and Porous Double-Network Hydrogel Effectively Induce the Differentiation of BMSCs into Osteochondral Tissue In Vitro for Potential Application in Cartilage Repair.

At present, it is a considerable challenge to mimic the complex architecture of osteochondral (OC) tissue. In this study, a porous and gradient mineralized double-network hydrogel is synthesized and used to induce bone marrow mesenchymal stem cells (BMSCs) to differentiate into the desired OC tissue depending only on the material and mechanical properties. Physical and chemical characterizations show that hydroxyapatite nanoparticles grow and fill into the pores of the hydrogel, and their content presents a gradient change in different layers of hydrogel. The synthesized hydrogel has excellent mechanical properties and the compression strength with different mineralization degrees varies from 27 to 380 kPa, which fully meets the needs of increased mechanical strength of articular cartilage from the surface to the deep layer. Besides, the synthesized hydrogel has good biocompatibility that can promote the proliferation and growth of BMSCs. More importantly, the results of histochemistry, immunohistochemistry, and real time polymerase chain reaction show that gradient mineralized hydrogel can induce BMSCs to differentiate into the desired chondrocytes and osteoblasts in different layers of hydrogels, indicating that OC tissues can be successfully constructed through a simple induction differentiation of gradient mineralized hydrogel.