A "Mesoporous Oxygen Chamber" Scaffold with Antibacterial and Early Immunomodulatory Effect for Promoting Bone Regeneration.

Abstract

Regeneration of bone defects are frequently hindered by severe inflammation, immunogenicity after bone repairing material implantation, and microbial infections. Oxygen therapy is reported to downregulate the levels of pro-inflammatory cytokines and proteases, alleviating inflammation and promoting regeneration. Mesoporous bioactive glass (MBG) is marked by its osteoinductivity and mesoporous structure for drug delivery. In this study, an oxygen-loaded and antimicrobial peptide (AP)-functionalized scaffold (MBGAPO) is synthesized and proven with sufficient oxygen-delivery capacity of mesopores, promising antibacterial ability against E.coli and MRSA, multiplex-immunomodulatory effects, and potent osteoinductivity both in vitro and in vivo. In cranial defect models of mouse and rat, MBGAPO created a mild immune microenvironment that accelerated inflammation alleviation and facilitated immune cells transformation toward anti-inflammatory phenotypes in the initial stage of bone regeneration, and exhibited a superior immune modulatory effect than Bio-oss (an FDA-approved bone substitute). In vivo results indicated that oxygen delivery promoted bone regeneration within the scaffold, and AP functionalization facilitated the bridging of surrounding tissue in the defect area. In summary, mesoporosity-based oxygen delivery is first proven as a promising osteoimmunology therapeutic strategy, and its combination with antimicrobial peptides can be extended to more regenerative and disease treatment applications that may arouse broader interests of researchers.