Electrospinning Machine | Point-of-care treatment of acute skin wound by portable in-situ electrospinning nanofiber dressings with rapid hemostasis, anti-infection, and angiogenesis effects

Acute trauma caused by traffic accidents and natural disasters is increasingly common, bringing multifaceted challenges such as irregular wound bleeding and susceptibility to microbial infection. Researchers from the Shanghai Institute of Ceramics, Chinese Academy of Sciences, and Shanghai Xuhui District Stomatological Hospital collaborated to prepare an in-situ electrospun zein/polyvinylpyrrolidone nanofiber bioactive dressing incorporated with tannic acid-based nano-copper (CTZP). CTZP exhibited rapid hemostatic performance in a rat tail amputation model. In vitro coagulation tests verified that CTZP could achieve coagulation within 1 minute. The study found that CTZP activates platelets via the PI3K-Akt signaling pathway through the expression of TBXAS1. Furthermore, in vitro tube formation experiments indicated that CTZP has pro-angiogenic effects. qPCR results showed that the zein/PVP (ZP) substrate could promote angiogenesis by enhancing VEGF generation. Moreover, the incorporation of copper-tannic acid nanoparticles (Cu@TA) further strengthened this VEGF promotion and synergistically up-regulated eNOS expression via the PI3K-Akt signaling pathway, which is the same pathway involved in platelet activation. Additionally, in vivo immunohistochemical results confirmed the upregulation of angiogenesis-related proteins VEGF and CD31.

Furthermore, the Cu@TA nanoparticles enable the CTZP dressing to possess strong antibacterial activity through hydroxyl radical generation via a Fenton-like reaction and copper ion release. Ultimately, in vivo experiments using a Staphylococcus aureus-infected rat wound model confirmed that CTZP has a significant wound healing effect. These findings promote the practical application of in-situ electrospinning technology in acute trauma care, providing theoretical and material insights for designing hemostatic, anti-infective, and angiogenic wound dressings. The related research results, entitled "Point-of-care treatment of acute skin wound by portable in-situ electrospinning nanofiber dressings with rapid hemostasis, anti-infection, and angiogenesis effects," were published in the journal Bioactive Materials.

Scheme 1. In-situ electrospun zein/PVP composite nanofiber wound dressing doped with tannic acid-based copper nanoparticles enhances wound healing through hemostasis, antibacterial, and angiogenesis effects.

Figure 1. Screening zein/PVP fibers with different component ratios. Hemostatic performance of various samples evaluated by in vitro coagulation tests, including blood clotting index (A), red blood cell attachment (B), and platelet attachment (C). Schematic diagram of the in vivo open bleeding rat tail amputation model (D) and corresponding representative photographs of different groups within 3 minutes (E). Quantitative results of hemostasis rate after 3 minutes for each group (F). SEM morphology of P1Z3 (G) fibrous membranes at different concentrations. Fiber diameter distribution of P1Z3 at 30 wt% (H) and 40 wt% (I). Quantitative record of blood loss in a rat severe liver injury model (J). Image of in-situ electrospun ZP nanofiber membrane in rat subcutaneous tissue (K).

Figure 2. Characterization of Cu@TA NPs, ZP, and CTZP. Morphology of Cu@TA in HAADF-STEM (A) and corresponding high-magnification EDS imaging (B). XRD patterns (C) and FTIR spectra (D) of Cu@TA, ZP, and CTZP. (E) SEM morphology and elemental mapping of ZP. (F) SEM morphology and corresponding elemental mapping of CTZP. (G) Ratio of Cu+/Cu2+ ions after Cu@TA incubation in 75% ethanol and acetate buffer at pH=4.5, respectively. Absorbance in the 550-750 nm wavelength range (H) and electron paramagnetic resonance for •OH detection (I) of Cu@TA NPs in TMB test at pH=4.5 vs. pH=7.4 acetate buffer. (J) Cumulative copper ion release from CTZP under different pH conditions. (K) Inverted photographs of rat whole blood after contact with ZP and CTZP nanofiber membranes for 1 min. (L) Representative optical photographs of freshly prepared and self-assembled precursor solutions.

Figure 3. Antibacterial activity and cytocompatibility of ZP and CTZP. (A) Representative agar plate photographs of S. aureus colonies in Control, ZP, CTZP0.5, CTZP-1.0, and CTZP-1.5 groups, (B) Corresponding antibacterial rate against S. aureus. (C) Representative morphology of S. aureus co-cultured with or without CTZP-1.0. (D) Cell proliferation of HUVECs co-cultured with different samples for 24, 72, and 120 hours. (E) Live/dead cell staining fluorescence images of HUVECs co-cultured with ZP and CTZP-1.0 for 24 hours.

Figure 4. Evaluation of cell migration and angiogenesis properties. Cell migration images of L929 (A), and quantitative analysis of cell migration rate (B) for Control, ZP, and CTZP at 24 and 48 h. In vitro tube formation assay of HUVECs at 6 hours (C) for Control, ZP, and CTZP groups, and corresponding quantitative analysis of node numbers (D). Expression levels of angiogenesis-related genes, including endothelial nitric oxide synthase (eNOS) (E) and kinase insert domain receptor (KDR) (F).

Figure 5. CTZP promotes infected wound healing in vivo. (A) Schematic diagram of in vivo experiments and in-situ electrospinning of CTZP at the wound site. After S. aureus infection on day 1, nanofiber dressings were applied in-situ on day 0, then rat skin tissues were collected on days 1, 4, 7, and 14. (B) Wound photographs before and after in-situ electrospinning of CTZP. (C) Representative agar plate images of S. aureus on day 1 and day 4 for Control, ZP, and CTZP groups. Representative photographs of wound areas (D) and corresponding wound healing rates (E) for Control, ZP, and CTZP groups (n=4). Representative hematoxylin and eosin (H&E) staining images (F) of Control, ZP, and CTZP groups on days 1, 4, 7, and 14, and corresponding granuloma thickness on day 14 (G). Giemsa staining images (H) on day 1 and day 4, and Masson's trichrome staining images (I) on day 7 and day 14 for Control, ZP, and CTZP groups. Immunohistochemical staining images of VEGF and CD31 (J) on day 14 for Control, ZP, and CTZP groups, and corresponding quantitative analysis of CD31 (K) and VEGF (L).

Figure 6. Potential mechanism of action of CTZP. (A) Structural interactions among Cu@TA, Zein, and PVP within CTZP, and the possible tissue adhesion mechanism of CTZP. (B) Hypothesized mechanism by which CTZP accelerates wound healing through hemostasis, antibacterial action, re-epithelialization, and angiogenesis.

Conclusion
In summary, this paper presents an in-situ electrospun CTZP nanofiber dressing composed of zein/PVP and Cu@TA nanoparticles. Using medically disinfected alcohol as a green solvent eliminates the risks associated with organic solvents and simplifies the material preparation process, facilitating the practical application of portable electrospinning. The biocompatible CTZP nanofiber dressing activates platelets via highly expressed TBXAS1, exhibiting rapid hemostatic performance. Mechanistically, Cu@TA NPs, on one hand, promoted the intrinsic VEGF-promoting ability of ZP, and on the other hand, endowed eNOS regulatory activity, which could synergistically promote angiogenesis. Interestingly, both platelet activation and the VEGF signaling pathway are mediated by the highly expressed PI3K-Akt signaling pathway. Additionally, the incorporation of Cu@TA NPs imparted effective antibacterial activity and enhanced fibroblast activity. This study provides a theoretical and material basis for portable in-situ electrospun hemostatic, antibacterial, and pro-angiogenic dressings for point-of-care treatment of acute wounds.

Original link:https://doi.org/10.1016/j.bioactmat.2025.08.020