In-situ Enzymatic Reaction Generates Magnesium-Based Mineralized Microspheres with Superior Bioactivity for Enhanced Bone Regeneration.

Bone is a naturally mineralized tissue with a remarkable hierarchical structure, and the treatment of bone defects remains challenging. Microspheres with facile features of controllable size, diverse morphologies, and specific functions, display amazing potentials for bone regeneration. Herein, inspired by natural biomineralization, w e report a novel enzyme-catalyzed reaction to prepare magnesium-based mineralized microspheres. First, silk fibroin methacryloyl (SilMA) microspheres w ere prepared using a combination of microfluidics and photocrosslinking. Then, the alkaline phosphatase (ALP)-catalyzed hydrolysis of adenosine triphosphate (ATP) w as successfully used to induce the formation of spherical magnesium phosphate (MgP) in the SilMA microspheres. These SilMA@MgP microspheres displayed uniform size, rough surface structure, good degradability, and sustained Mg2+ release properties. Moreover, the in vitro studies demonstrated the high bioactivities of SilMA@MgP microspehres in promoting the tube formation of HUVECs, and proliferation, migration and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Transcriptomic analysis showed that the osteoinductivity of SilMA@MgP microspheres might be related to the activation of the PI3K/Akt signaling pathway. Finally, the bone regeneration enhancement units (BREUs) w ere designed and constructed by inoculating BMSCs onto SilMA@MgP microspheres, efficiently promoting in vivo bone regeneration. In summary, w e created a novel cell-microsphere complex with superior bioactivity for bone regeneration and demonstrated a new biomineralization strategy for designing biomimetic materials with defined structures and combination functions. This article is protected by copyright. All rights reserved.