Biocompatible, antibacterial, anti-inflammatory, and tissue regenerative smart dressings are in urgent need for infected skin wound repair in clinics. Portable in situ 3D-electrospun technology has the great advantage of direct deposition of required smart dressing on wound surfaces. Here, we fabricated a copper peptide (GHK-Cu) and quaternium-73 (Pionin) dual-drug-loaded polyvinyl butyral (PVB)/polyvinylpyrrolidone (PVP) smart nanofibers dressing using in-situ electrospinning technology for skin wound repair. The physicochemical properties and biological activities of smart dressing were extensively analyzed. In vivo biocompatibility, anti-oxidant, anti-inflammatory, and antimicrobial activities of smart dressing were analyzed during wound healing. Stable and homogeneous PVB/PVP nanofiber smart dressing with uniformly distributed GHK-Cu and Pionin and anabolic biological activities was obtained. Biocompatible smart dressing gave a sustained release of GHK-Cu and Pionin, promoted the migration and adhesion of dermal fibroblasts and keratinocytes, and showed anti-oxidant and anti-apoptotic effects in vitro and in vivo. Smart dressing exerted anti-inflammatory properties via M1 to M2 macrophage phenotype switching and effectively promoted wound healing. Pionin released from smart dressing not only killed but also inhibited the expression and delivery of virulence factor expression and bacteria adhesion. During wound healing, smart dressing promoted the proliferation of cells in the epidermal tissue, epithelial tissue remodeling, granulation tissue growth, neovascularization, and M2 macrophage polarization. Moreover, this smart dressing scavenged excess reactive oxygen species, increased SOD3 and SIRT1 expression, and repaired peroxidized tissue, consequently promoting wound healing. In summary, our results indicate that GHK-Cu/Pionin-loaded in situ electrospun PVB/PVP smart dressing promotes wound healing via anti-oxidant, anti-inflammatory, antimicrobial, and tissue regenerative effects, suggesting clinical application of this smart dressing for complicated skin wound healing.

中文翻译：

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负载 GHK-Cu/Pionin 的原位静电纺丝 PVB/PVP 智能敷料通过抗氧化、抗炎、抗菌和组织再生作用促进伤口愈合


临床上感染皮肤伤口修复急需生物相容、抗菌、抗炎、组织再生的智能敷料。便携式原位 3D 静电纺丝技术具有将所需智能敷料直接沉积在伤口表面的巨大优势。在这里，我们利用原位静电纺丝技术制造了铜肽（GHK-Cu）和季铵盐73（Pionin）双载药聚乙烯醇缩丁醛（PVB）/聚乙烯吡咯烷酮（PVP）智能纳米纤维敷料，用于皮肤伤口修复。对智能敷料的理化特性和生物活性进行了广泛的分析。分析伤口愈合过程中智能敷料的体内生物相容性、抗氧化、抗炎和抗菌活性。获得稳定均质的PVB/PVP纳米纤维智能敷料，其GHK-Cu和Pionin分布均匀，具有合成代谢生物活性。生物相容性智能敷料能够持续释放GHK-Cu和Pionin，促进真皮成纤维细胞和角质形成细胞的迁移和粘附，并在体外和体内表现出抗氧化和抗凋亡作用。智能敷料通过M1到M2巨噬细胞表型转换发挥抗炎特性，有效促进伤口愈合。智能敷料释放的Pionin不仅可以杀死细菌，还可以抑制毒力因子表达和细菌粘附的表达和传递。在伤口愈合过程中，智能敷料促进表皮组织细胞增殖、上皮组织重塑、肉芽组织生长、新生血管形成和M2巨噬细胞极化。 此外，这种智能敷料还能清除多余的活性氧，增加SOD3和SIRT1的表达，修复过氧化组织，从而促进伤口愈合。总之，我们的结果表明，GHK-Cu/Pionin原位静电纺PVB/PVP智能敷料通过抗氧化、抗炎、抗菌和组织再生作用促进伤口愈合，提示这种智能敷料在复杂情况下的临床应用皮肤伤口愈合。