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Despite the interaction between bone marrow mesenchymal stem cells (BMSCs) and macrophages has been found to play a critical role in repairing bone defects, it remains a challenge to develop a desirable tissue engineering scaffold for synchronous regulation of osteogenic differentiation and macrophage polarization. Herein, this study proposed a novel strategy to treat bone defects based on three-dimensional Gelatin Methacryloyl Inverted Colloidal Crystal (3D GelMA ICC) scaffold and an active 15-hydroxyprostaglandin dehydrogenase (15-PGDH) inhibitor SW033291. Specifically, the 3D GelMA ICC scaffolds were firstly prepared by colloidal templating method, which displayed good cell attachment and promoted intercellular interaction among macrophage and BMSCs due to its uniform pore interconnectivity. By combined use of SW033291, the release of Prostaglandin E2 (PGE2) from BMSCs on the GelMA ICC scaffold was significantly upregulated and macrophages M2 polarization was markedly increased. In turn, BMSCs proliferation and osteogenic differentiation was further enhanced by paracrine regulation of M2 macrophage, and thus finally caused more in vivo new bone formation by shaping up a pro-regenerative local immune microenvironment surrounding GelMA ICC scaffold. Our findings demonstrate the potential of 3D GelMA ICC scaffolds combined with SW033291 to become an effective tissue engineering strategy for bone regeneration.

3D GelMA ICC Scaffolds Combined with SW033291 for Bone Regeneration by Modulating Macrophage Polarization