Spatiotemporally Programming Microenvironment to Recapitulate Endochondral Ossification via Greenhouse-Inspired...

Various biomaterials have been developed to address challenging critical-sized bone defects. However, most of them focus on intramembranous ossification (IMO) rather than endochondral ossification (ECO), often resulting in suboptimal therapeutic outcomes. Drawing inspiration from the functionality of the greenhouse ecosystem, herein a bionic niche is innovatively crafted to recapitulate the ECO process. This niche consists of three hierarchical components: an embedded microchannel network that facilitates cell infiltration and matter exchange, a polydopamine surface modification layer with immunomodulatory functions, and an ECO-targeted delivery system based on mesoporous silica nanoparticles. Through spatiotemporally programming of the microenvironment, the bionic niche effectively recapitulates the key stages of ECO. Notably, even in the rat calvaria, a region well-known for IMO, the bionic niche is capable of initiating ECO, evident by cartilage template formation, leading to efficient bone regeneration. Taken together, this study introduces prospective concepts for designing next-generation ECO-driven biomaterials for bone tissue engineering.