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Abstract:
The human skin is highly susceptible to bacterial infections and inflammation when its integrity is disrupted. Treatment of infected wounds is a big challenge in modern medicine, and rising antibiotic resistance motivates the development of antibiotic-free therapies. Here, we present a stimuli-responsive wound dressing that integrates carboxylated eggshell membrane (ESM) with electrosprayed tannic acid/iron (TAFe) particles trapped between electrospun Poly-L-lactide-caprolactone (PLCL) layers and precisely laser-structured to increase porosity and fit the wound size. The TAFe exhibits stable photothermal conversion and antioxidant activity, eradicating more than 99.5% of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), while maintaining high biocompatibility in vitro. In an infected rat model, the sandwich-like ESMmod/PLCL/TAFe dressing accelerated closure and achieved near-complete healing, with residual wound area <1% by day 14. Analysis shows that the material promotes M2-mediated reparative microenvironment, which, in consequence, suppresses TNFα and IL-6, a pro-inflammatory cytokines, and enhances angiogenesis through increased CD31 and VEGF levels. Moreover, a more organized collagen structure and less scarring were found in the wound bed. Importantly, the material is partially derived from waste, aligning with circular economy principles and reducing resource burden. The versatile composite offers an antibiotic-free strategy that disinfects, modulates inflammation, and promotes regeneration of infected wounds.

Keywords:
circular economy, immunomodulated wound healing, laser-engineered microenvironment, macrophage polarization orchestration, photothermal anti-bacterial activity

Abstract:
The disruption of homeostasis in the tissue microenvironment following skin injury necessitates the provision of a supportive niche for cells to facilitate the restoration of functional tissue. A meticulously engineered cell-scaffold biointerface is essential for eliciting the desired cellular responses that underpin therapeutic efficacy. To address this, we fabricated an electrospun poly-(L-lactide) (PLLA) cell scaffold enriched with graphene oxide (GO) and gold nanoparticles (AuNPs). Comprehensive characterization assessed the scaffolds’ microstructural, elemental, thermal, and mechanical properties. In vitro investigations evaluated the biocompatibility, adhesive and regenerative capabilities of the scaffolds utilizing human keratinocytes (HEKa), fibroblasts (HFFF2), and reconstructed epidermis (EpiDerm™) models. The results demonstrated that the incorporation of the GO-Au composite substantially altered the nanotopography and mechanical properties of the PLLA fibers. Cells effectively colonized the PLLA + GO-Au scaffold while preserving their structural morphology. Furthermore, PLLA + GO-Au treatment resulted in increased epidermal thickness and reduced tissue porosity. The scaffold exerted a significant influence on actin cytoskeleton architecture, facilitating cell adhesion through the upregulation of integrins, E-cadherin, and β-catenin. Keratinocytes exhibited enhanced secretion of growth factors (AREG, bFGF, EGF, EGF R), while fibroblast secretion remained stable. These findings endorse the scaffold’s potential for regulating cellular fate and preventing hypertrophic tissue formation in skin tissue engineering.

Keywords:
Wound healing,Electrospun fibers,Graphene oxide,Gold nanoparticles,Proregenerative cell scaffold