Highly porous cryogel composed of bone matrix derived dECM and laponite for vascularized bone regeneration

Abstract Regenerating injured bone tissue remains a critical challenge, necessitating the development of functional scaffolds to support the intricate process of neo-bone growth. Various natural and synthetic materials combined with bioactive factors have been explored, but decellularized extracellular matrices (dECM) continue to stand out as excellent scaffolding materials due to their intrinsic bioactivity. In this study, we fabricated cryogel-type scaffolds with interconnected pores from decellularized bone ECM (DBM) after mineral removal. To enhance their angiogenic and osteogenic properties, we incorporated laponite (LAP), which is a kind of lithium magnesium silicate. For improved mechanical strength, the DBM was modified with methacrylic anhydride to enable chemical crosslinking among collagen macromolecules. The addition of LAP further contributed to mechanical reinforcement. The resulting composite cryogel demonstrated exceptional cyclic compressive stability, maintaining structural integrity and mechanical strength under repetitive loading. In vitro assays revealed its significant promotion of vascularization and osteogenic differentiation. In vivo studies using a rat cranial defect model confirmed substantial new bone formation and enhanced regeneration of vascularized bone tissue. These findings highlight the potential of bone-derived dECM materials for effective in situ bone regeneration.