Bioactive Poly(octanediol‐citrate‐polyglycol) Accelerates Skin Regeneration through M2 Polarization Immunomodulating and Early Angiogenesis

Abstract The inhibition of inflammation and the promotion of early angiogenesis are paid much attention in skin tissue engineering. Citric acid‐based biomaterials are widely used in tissue engineering due to their bioactive structure and biocompatibility, but there are few studies on investigating their role and mechanism in wound repair and skin regeneration. Herein, the potential anti‐inflammation mechanism of poly(octanediol‐citrate‐polyglycol) (POCG) copolymer is reported in regulating skin wound repair. It is found that POCG can modulate macrophages phenotype through downregulating the expression of proinflammatory cytokines (tumor necrosis facor‐α ( Tnf‐α ), Interleukin‐1β ( IL‐1β ), and Interleukin‐6 ( IL‐6 ) and polarizing macrophages to anti‐inflammatory (M2) phenotype. POCG can promote endothelial cell vascularization by increasing the expression of angiogenesis factors (vascular endothelial growth factor ( Vegf ) and cluster of differentiation 31CD31) mediated by the macrophage polarization. The in vivo study shows that POCG can accelerate skin wound repair through suppressing the acute inflammation and inducing early angiogenesis through the polarization modulation. Furthermore, the POCG polymer has good biocompatibility for both immune cells and tissue cells. This study may provide the important theoretical support on the bioactivity of citrate‐based biomaterials and expanding their applications in tissue engineering.