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

Abstract

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 copperepigallocatechin 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 proinflammatory 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.

Green Starch-Based Hydrogels with Excellent Injectability, Self-Healing, Adhesion, Photothermal Effect, and Antibacterial Activity for Promoting Wound Healing

“…Thereupon, the photothermal conversion efficiency (η) of CG NSs was calculated to be 40.83% (Figure S3f), which was significantly higher than most common photothermal agents including amino-functionalized molybdenum disulfide nanosheets (NMNSs) (37.9%), Au nanoshells (13.0%), Au nanorods (21.0%), DSPN5 (30.8%), and so forth. Additionally, studies have reported that the combination of gallic acid and Cu ions exhibits antibacterial, antioxidant, and anti-inflammatory properties. , These results manifested the great potential of using such CG NSs as a PTT material for killing bacteria and accelerating wound healing under NIR laser irradiation. CA, a plant-based compound, is usually regarded as a natural antibacterial agent, which can effectively inhibit bacterial growth by inhibiting bacterial efflux pumps, reducing biofilm formation, inhibiting microbial ATPase, and inhibiting microbial activity .…”

“…Additionally, studies have reported that the combination of gallic acid and Cu ions exhibits antibacterial, antioxidant, and anti-inflammatory properties. 36,37 These results manifested the great potential of using such CG NSs as a PTT material for killing bacteria and accelerating wound healing under NIR laser irradiation. CA, a plant-based compound, is usually regarded as a natural antibacterial agent, which can effectively inhibit bacterial growth by inhibiting bacterial efflux pumps, reducing biofilm formation, inhibiting microbial ATPase, and inhibiting microbial activity.…”

Recent advances in fabrication of dECM-based composite materials for skin tissue engineering

“…Moreover, the composite scaffold demonstrated excellent hemostatic effect and hemocompatibility, thus showing an essential potential in skin engineering. Hu et al reported a multifunctional dECM-MA-based 3D printing hydrogel scaffold embedded with copper epigallocatechin gallate nano-capsules for diabetic wound management ( Hu et al, 2023 ). The cellular experiments indicated that the multifunctional 3D platform showed favorable anti-inflammatory capacity and good biocompatibility, which could accelerate vascularization and promote cell migration and invasion.…”