Automated Electrospinning Equipment| FGF mimetic peptide-modified electrospun nanocomposite fibrousmembranes for accelerating infectious diabetic wound healing bysynergistic antibacterial and pro-angiogenesis effects

Chronic diabetic skin wounds have become a major global public health challenge due to healing impairments caused by bacterial infections and insufficient vascular regeneration. Biomimetic ultrafine composite fibers show great potential in promoting wound healing. Copper (Cu), as an essential trace element in humans, possesses both broad-spectrum antibacterial and pro-angiogenic effects, while fibroblast growth factor-mimetic peptide (FGFp) can effectively promote cell proliferation and migration. However, the development of highly efficient fiber membrane skin tissue engineering scaffolds loaded with active factors still faces significant challenges due to the rapid release behavior of these two active factors in ultrafine fibers.

Recently, Assistant Professor Fang Zhou and Professor Yingjun Xu from the College of Textiles and Clothing at Qingdao University published their latest research titled "FGF mimetic peptide-modified electrospun nanocomposite fibrous membranes for accelerating infectious diabetic wound healing by synergistic antibacterial and pro-angiogenesis effects" in the journal Materials Today Bio. The researchers combined FGFp with poly(L-lactide-co-ε-caprolactone) (PLCL) electrospun fiber membranes loaded with Cu/catechol-derived resin nanoparticles (CuCFR) through hydrothermal synthesis, electrospinning, and surface chemical modification processes to create an efficient composite fiber membrane material (CuCFR-FGFp). This membrane achieves sustained release of both active factors (FGFp and Cu2+) for up to 14 days through surface chemical grafting of FGFp and internal physical encapsulation of CuCFR nanoparticles, demonstrating excellent antibacterial infection resistance and lumen formation promotion capabilities. In a bacterial-infected diabetic mouse wound model, the synergistic effect of Cu2+ and FGFp in the fiber membrane significantly enhanced vascular marker expression and wound healing capacity. This study provides new insights for developing long-term, highly efficient drug-loaded composite fiber skin tissue engineering scaffolds.

Figure 1: Schematic diagram of the preparation of CuCFR nanoparticles and CuCFR-FGFp composite fiber membrane

Figure 2: Characterization of CuCFR nanoparticles and functionalized CuCFR-FGFp composite fiber membrane

Using a two-step strategy, CuCFR nanoparticles were prepared and encapsulated within the electrospun ultrafine fibers. Subsequently, FGFp was chemically conjugated to the fiber membrane surface via disulfide bond-mediated click chemistry, maintaining good porous ultrafine fiber morphology and excellent tensile properties (tensile strength of 6.2 MPa and elongation of 317%), which provided essential support for the sustained release and bioactivity of the two active factors.

Figure 3: Antibacterial properties of the prepared CuCFR-FGFp composite membrane

Thanks to the unique structure of CuCFR nanoparticles, the CuCFR-FGFp composite membrane could continuously release Cu2+ for 14 days. The released Cu2+ increased cell membrane permeability, causing the surfaces of Staphylococcus aureus and Escherichia coli to become rough, distorted, and collapsed, with bacterial contents leaking out, thereby effectively inhibiting their growth and reproduction (antibacterial rate >98%). The introduction of FGFp did not significantly affect the antibacterial activity.

Figure 4: Effects of the prepared CuCFR-FGFp composite membrane on fibroblast proliferation and endothelial cell tube formation

In vitro biosafety evaluation results showed that the CuCFR/FGFp composite membrane had a hemolysis rate below 1% and exhibited good cell viability after 24 and 72 hours of co-culture with skin fibroblasts and vascular endothelial cells. Benefiting from the synergistic effect of Cu2+ and FGFp, the CuCFR/FGFp fiber membrane more significantly promoted the proliferation and migration of fibroblasts and endothelial cells, as well as the tube-forming ability of endothelial cells.

Figure 5. Evaluation of the diabetic wound healing capacity of CuCFR-FGFp composite membrane in bacterial-infected wounds in vivo

In vivo study results demonstrated that in diabetic mice with infected wounds treated with the CuCFR/FGFp fiber membrane, the newly formed epidermis thickened to approximately 43.7 µm, collagen deposition increased significantly by 3.4 times, and skin appendages such as hair follicles increased markedly, effectively promoting wound healing. Additionally, the released Cu2+ played roles in resisting bacterial infection and promoting macrophage polarization in vivo (reduced CD86 expression and increased CD206 expression). Under the synergistic action of Cu2+ and FGFp, the composite membrane significantly enhanced the expression levels of vascular markers (CD31 and α-SMA) by approximately 3 times, effectively accelerating the healing of infected wounds in diabetic mice and demonstrating tremendous application potential in the treatment of chronic diabetic skin wounds.

Paper link: https://www.sciencedirect.com/science/article/pii/S2590006425004375?via%3Dihub