Magnesium-doped biomimetic intrafibrillar mineralized decellularized extracellular matrix cryogel with oriented microchannel for vascularized bone regeneration.

Despite the significant advancements in the development of biomimetic materials for bone repair, accurately replicating the complex characteristics of natural bone tissue across multiple scales remains a challenge. Inspired by the intrinsic hierarchical structure of bone tissue, a multi-dimensional biomimetic strategy was developed by restoring the component composition, simulating biomineralization processes, mimicking hierarchical structures, and imparting essential biological functions to improve bone regeneration efficiency. Specifically, directional freezing technology followed by photopolymerization of a precursor solution containing methacrylated hyaluronic acid and decellularized extracellular matrix was utilized to fabricate construct with oriented microchannels, and subsequent magnesium-doped polymer induced liquid precursor mineralization to successfully fabricate scaffolds (Mg-MCG) that closely mimicked the natural bone tissue composition and structure. Studies revealed that the scaffold was fabricated with amenable mineral content (50-60%), matrix stiffness, and hierarchical structure similar to bone tissue, which in turn facilitated rapid and directed cell infiltration to create an oriented and parallel cell distribution. In vitro and in vivo studies further demonstrated the ability of the scaffold to regulate H-type vessels regeneration and promoting vascularized bone regeneration in addition to its excellent biodegradability. Based on an in-depth understanding of bone hierarchical characteristics, this strategy achieved collaborative biomimicry across compositional components, structural features, and functional attributes, significantly enhancing the adaptive regeneration between the biomimetic scaffold and bone tissue.