Antibacterial Conductive Polysaccharide-Based Hydrogel Microneedle Patches Accelerate Infected Diabetic Wound Healing through Anti-Inflammatory and Pro-Angiogenesis

伤口愈合 透明质酸 材料科学 活性氧 血管生成 再生(生物学) 生物医学工程 慢性伤口 抗菌活性 皮肤修复 自愈水凝胶 血管内皮生长因子 巨噬细胞 巨噬细胞极化 免疫系统 细胞毒性 癌症研究 成纤维细胞 炎症 伤口闭合 药理学 组织粘连 新生血管 细胞内 疤痕 光敏剂 生物材料 真皮成纤维细胞 表皮葡萄球菌 糖尿病 成纤维细胞生长因子
作者
Zhiyang Gan,Xiaxi Pan,Yongbin Xu,Qingsu Cheng,Liming Ge,Zhonglang Yu,Changdao Mu,Zhilang Xu,Defu Li
出处
期刊:ACS Applied Materials & Interfaces [American Chemical Society]
卷期号:18 (15): 21682-21699
标识
DOI:10.1021/acsami.6c01009
摘要

Diabetic ulcers (DUs) are a main category of nonhealing chronic wounds that tend to be vulnerable and prone to recurrence, posing a significant clinical challenge for DUs healing. DUs are frequently plagued by bacterial infections, oxidative stress, persistent inflammation, suppressed angiogenesis, and reduced growth factor expression, ultimately leading to persistent barriers to tissue regeneration and even amputation. Herein, we developed a multifunctional polysaccharide-based conductive hydrogel microneedle patch (MN-EP) integrating hyaluronic acid (HA) needle shafts, carboxymethyl chitosan-oxidized HA (CMCS–OHA) hydrogel backing, and oregano essential oil (OEO)-loaded polypyrrole (PPy) nanoparticles (EP NPs). MN-EP exhibited sufficient mechanical strength to penetrate stratum corneum, favorable conductivity matching skin tissue due to EP NPs, broad-spectrum antibacterial activity (nearly 100% against Staphylococcus aureus and Escherichia coli ), and potent antioxidant capacity. It was demonstrated that MN-EP can scavenge intracellular reactive oxygen species (ROS), induce macrophage polarization toward the anti-inflammatory M2 phenotype, and promote fibroblast migration. In diabetic rats with infected full-thickness wounds, the electroactive MN-EP effectively eliminated harmful microorganisms at the wound site and modulated the immune microenvironment, thereby accelerating the resolution of inflammation, enhancing collagen deposition, and upregulating angiogenesis markers (CD31, VEGF), which promoted vascular and tissue regeneration and accelerated wound closure (98.28% by day 14). Overall, the multifunctional conductive hydrogel microneedle platform with antibacterial, anti-inflammatory, and pro-angiogenic properties represents a promising strategy for infected chronic diabetic wound healing.
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