Biomimetic Mineralized Decellularized Adipose Tissue Accelerates Bone Repair by Immunomodulation and Dual Ossification

Biomimetic mineralization as a promising method offers a bottom-up strategy for creating new organic-inorganic hybrid materials for treating bone defects. However, it is insufficient for bone regeneration, a complex biological procedure involving an interaction between osteogenesis and microenvironment. Herein, a biomimetic mineralized scaffold derived from decellularized adipose tissue modified with polyphenol tannic acid (TA@mDAT) is developed, drawing inspiration from the regulation of the microenvironment and the biomimetic strategy. Besides its enhanced mechanical properties by mineralization, the shape-memory effect of the biomimetic mineralized decellularized adipose tissue (mDAT) is also improved, due to the crosslinking structure between decellularized adipose tissue (DAT) and tannic acid (TA). Besides, the TA@mDAT scaffold exhibits excellent biocompatibility and immunomodulation effect, high efficacy in guiding bone regeneration via intramembranous and endochondral ossification, and enhanced H-type vessel formation. Furthermore, the enhanced expression of Dll4 and Hey1 involving the Notch1 signaling pathway is detected in the regenerated bone, indicating that the Dll4-Notch1 signaling pathway may play an important role in bone regeneration. Thus, this work provides a promising method for bone regeneration by triggering periosteal osteogenesis and H-type vessel formation and revealing a potential mechanism in the osteogenic process.