Copper-Epigallocatechin Gallate Enhances Therapeutic Effects of 3D-Printed Dermal Scaffolds in Mitigating Diabetic Wound Scarring

• Published in: ACS applied materials & interfaces Vol. 15; no. 32; pp. 38230 - 38246
• Main Authors: Hu, Yanke, Xiong, Yahui, Zhu, Yongkang, Zhou, Fei, Liu, Xiaogang, Chen, Shuying, Li, Zhanpeng, Qi, Shaohai, Chen, Lei
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 16.08.2023
• Subjects: Biological and Medical Applications of Materials and Interfaces; in situ tissue regeneration; metal-polyphenol capsule; split-thickness skin graft; extracellular matrix; diabetic wound healing
• ISSN: 1944-8244; 1944-8252
• DOI: 10.1021/acsami.3c04733

Morbid dermal templates, microangiopathy, and abnormal inflammation are the three most critical reasons for the scarred healing and the high recurrence rate of diabetic wounds. In this present study, a combination of a methacrylated decellularized extracellular matrix (ECMMA, aka EM)-based hydrogel system loaded with copper-epigallocatechin gallate (Cu-EGCG) capsules is proposed to fabricate bio-printed dermal scaffolds for diabetic wound treatment. Copper ions act as a bioactive element for promoting angiogenesis, and EGCG can inhibit inflammation on the wound site. In addition to the above activities, EM/Cu-EGCG (E/C) dermal scaffolds can also provide optimized templates and nutrient exchange space for guiding the orderly deposition and remodeling of ECM. In vitro experiments have shown that the E/C hydrogel can promote angiogenesis and inhibit the polarization of macrophages to the M1 pro-inflammatory phenotype. In the full-thickness skin defect model of diabetic rats, the E/C dermal scaffold combined with split-thickness skin graft transplantation can alleviate pathological scarring via promoting angiogenesis and driving macrophage polarization to the anti-inflammatory M2 phenotype. These may be attributed to the scaffold-actuated expression of angiogenesis-related genes in the HIF-1α/vascular endothelial growth factor pathway and decreased expression of inflammation-related genes in the TNF-α/NF-κB/MMP9 pathway. The results of this study show that the E/C dermal scaffold could serve as a promising artificial dermal analogue for solving the problems of delayed wound healing and reulceration of diabetic wounds.