Modular Microgel‐Based Bioassembly Scaffold Induced Chondrogenic and Osteogenic Differentiation of BMSCs

Bioactive scaffolds capable of simultaneously repairing osteochondral defects remain a big challenge due to the heterogeneity of bone and cartilage. Currently modular microgel-based bioassembly scaffolds are emerged as potential solution to this challenge. Here, microgels based on methacrylic anhydride (MA) and dopamine modified gelatin (GelMA-DA) are loaded with chondroitin sulfate (CS) (the obtained microgel named GC Ms) or bioactive glass (BG) (the obtained microgel named GB Ms), respectively. GC Ms and GB Ms show good biocompatibility with BMSCs, which suggested by the adhesion and proliferation of BMSCs on their surfaces. Specially, GC Ms promote chondrogenic differentiation of BMSCs, while GB Ms promote osteogenic differentiation. Furthermore, the injectable GC Ms and GB Ms are assembled integrally by bottom-up in situ cross-linking to obtain modular microgel-based bioassembly scaffold (GC-GB/HM), which show a distinct bilayer structure and good porous properties and swelling properties. Particularly, the results of in vivo and in vitro experiments show that GC-GB/HM can simultaneously regulate the expression levels of chondrogenic- and osteogenesis-related genes and proteins. Therefore, modular microgel-based assembly scaffold in this work with the ability to promote bidirectional differentiation of BMSCs and has great potential for application in the minimally invasive treatment of osteochondral tissue defects.