In Situ Enzymatic Reaction Generates Magnesium‐Based Mineralized Microspheres with Superior Bioactivity for Enhanced Bone Regeneration

Abstract

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, a novel enzyme‐catalyzed reaction is reported to prepare magnesium‐based mineralized microspheres. First, silk fibroin methacryloyl (SilMA) microspheres are prepared using a combination of microfluidics and photo‐crosslinking. Then, the alkaline phosphatase (ALP)‐catalyzed hydrolysis of adenosine triphosphate (ATP) is successfully used to induce the formation of spherical magnesium phosphate (MgP) in the SilMA microspheres. These SilMA@MgP microspheres display uniform size, rough surface structure, good degradability, and sustained Mg2+ release properties. Moreover, the in vitro studies demonstrate the high bioactivities of SilMA@MgP microspehres in promoting the proliferation, migration, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Transcriptomic analysis shows that the osteoinductivity of SilMA@MgP microspheres may be related to the activation of the PI3K/Akt signaling pathway. Finally, the bone regeneration enhancement units (BREUs) are designed and constructed by inoculating BMSCs onto SilMA@MgP microspheres. In summary, this study demonstrates a new biomineralization strategy for designing biomimetic bone repair materials with defined structures and combination functions.

Boosting cartilage repair with silk fibroin-DNA hydrogel-based cartilage organoid precursor

“…In bone tissue engineering, Ouyang et al utilized hydrogel microspheres to construct osteo-callus organoids, achieving rapid bone defect repair within one month [ 49 ]. Additionally, Zhou et al created bone regeneration enhancement units using BMSC-loaded microspheres, facilitating swift bone defect healing [ 50 ]. In follicle tissue engineering, Hu et al employed gelatin methacryloyl microspheres loaded with mesenchymal and epithelial cells for rapid, large-scale hair regeneration [ 51 ].…”

Nanofibrous Microspheres: A Biomimetic Platform for Bone Tissue Regeneration

“…Temperature-responsive NFMS can be characterized by studying changes in polymer conformation, sol–gel transition temperatures, or mechanical properties as a function of temperature . Enzyme-responsive NFMS are typically characterized by monitoring enzymatic degradation kinetics or release profiles of bioactive molecules in the presence of relevant enzymes. , …”

“… 138 Enzyme-responsive NFMS are typically characterized by monitoring enzymatic degradation kinetics or release profiles of bioactive molecules in the presence of relevant enzymes. 139 , 140 …”