Combinatorial strategy for engineering cartilage and bone microtissues using microfluidic cell-laden microgels.

Abstract

Osteochondral defects refer to localized injuries affecting both the avascular cartilage and subchondral bone. Current treatments, such as transplantation or microfracture surgery, are hindered by limitations like donor availability and the formation of small, rigid fibrocartilage. Tissue engineering presents a promising alternative, yet challenges arise from limited oxygen and nutrient supply when fabricating human-scale tissue constructs. To address this, we propose assembling engineered micro-scale tissue constructs as building blocks for human-scale constructs. In this study, we aimed to develop bone and cartilage microtissues as building blocks for osteochondral tissue engineering. We fabricated placental stem cell (PSC)-laden microgels, inducing differentiation into osteogenic and chondrogenic microtissues. Utilizing a microfluidics chip platform, these microgels comprised a cell-laden core containing bone-specific and cartilage-specific growth factor-mimetic peptides, respectively, along with an acellular hydrogel shell. Additionally, we investigated the effect of culture conditions on microtissue formation, testing dynamic and static conditions. Results revealed over 85% cell viability within the microgels over 7 days of continuous growth. Under static conditions, approximately 60% of cells migrated from the core to the periphery, while dynamic conditions exhibited evenly distributed cells. Within 4 weeks of differentiation, growth factor-mimetic peptides accelerated PSC differentiation into bone and cartilage microtissues. These findings suggest the potential clinical applicability of our approach in treating osteochondral defects.