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.

Immunomodulatory hydrogels for skin wound healing: cellular targets and design strategy

“…When mixing POCG with chitosan and b-glycerophosphate, the prepared hydrogel demonstrated its effectiveness in promoting M2 macrophage polarization, reducing the expression of inflammatory factors, and regulating angiogenesis for defect wound healing. 146 4.1.4 Other hydrogels. In order to achieve a better antibacterial effect without delivering nanoparticles or drugs, Cheng et al developed a novel anti-bacterial cationic hydrogel (PHCI), which was achieved by a condensation reaction of trans-1,4-cyclohexanediamine with 1,3-dibromo-2propanol.…”

Biomaterial‐Based Therapeutic Approaches to Osteoarthritis and Cartilage Repair Through Macrophage Polarization

“…The macrophages stimulated vascularization and augmented skin repair and regeneration. [106] By targeting the polarization of macrophages for prevention and therapy in infectious diseases and cancers, the role of polymeric nanocarriers has been thoroughly reviewed. [107] It is also feasible to load peptides into polymeric scaffolds to modulate inflammation and angiogenic activity of the implant.…”

“…Citrate‐based biomaterial, poly(octanediol‐citrate‐polyglycol) regulated the polarization of macrophages towards the M2 state by downregulating TNF α, IL‐1β, andIL‐6. The macrophages stimulated vascularization and augmented skin repair and regeneration [106] . By targeting the polarization of macrophages for prevention and therapy in infectious diseases and cancers, the role of polymeric nanocarriers has been thoroughly reviewed [107] .…”

Multiple Coordination‐Derived Bioactive Hydrogel with Proangiogenic Hemostatic Capacity for Wound Repair

“…[1,2] proverbially investigated for the application in tissue regeneration because of their biomimetic elastomeric mechanical properties, good biocompatibility, degradability, and biological activities including anti-inflammation and angiogenesis. [31][32][33] In previous studies, our group has prepared poly (citrate-ethylene glycol) (PCG)-containing hybrid polymers and further confirmed their potential applications in gene delivery, wound repair, tumor therapy, and bone regeneration. [34][35][36] In this study, based on the good metal coordination capacity of SA and AL, the good bioactivity of PCG polymer as well as the multiple coordination of trivalent rare earth metal ions, we report a novel reversible dynamic multifunctional bioactive hydrogel with tailored anti-inflammation angiogenic activity for rapid hemostasis and wound repair (Figure 1).…”