Nanofiber Aerogels with Precision Macrochannels and LL‐37‐Mimic Peptides Synergistically Promote Diabetic Wound Healing

Abstract

Fast healing of diabetic wounds remains a major clinical challenge. Herein, this study reports a strategy to combine nanofiber aerogels containing precision macrochannels and the LL‐37‐mimic peptide W379 for rapid diabetic wound healing. Nanofiber aerogels consisting of poly(glycolide‐co‐lactide) (PGLA 90:10)/gelatin and poly‐p‐dioxanone (PDO)/gelatin short electrospun fiber segments are prepared by partially anisotropic freeze‐drying, cross‐linking, and sacrificial templating with 3D printed meshes, exhibiting nanofibrous architecture and precision micro‐/macrochannels. Like human cathelicidin LL‐37, W379 peptide at a concentration of 3 µg mL−1 enhances the migration and proliferation of keratinocytes and dermal fibroblasts in a cell scratch assay and a proliferation assay. In vivo studies show that nanofiber aerogels with precision macrochannels can greatly promote cell penetration compared to aerogels without macrochannels. Relative to control and aerogels with and without macrochannels, adding W379 peptides to aerogels with precision macrochannels shows the best efficacy in healing diabetic wounds in mice in terms of cell infiltration, neovascularization, and re‐epithelialization. The fast re‐epithelization could be due to the upregulation of phospho‐extracellular signal‐regulated kinase (p38 mitogen‐activated protein kinase) after treatment with W379. Together, the approach developed in this study could be promising for the treatment of diabetic wounds and other chronic wounds.

Copper–Cystine Biohybrid-Embedded Nanofiber Aerogels Show Antibacterial and Angiogenic Properties

“…The efficacy of similar aerogel types has been demonstrated in prior studies. 58,69 However, the present study delves into the effect of the gradual release of Cu 2+ from CuHARS embedded within the aerogels. This investigation explores their roles in fostering angiogenesis and delivering a short-term burst of antibacterial effect.…”

A Self-Healing Multifunctional Hydrogel System Accelerates Diabetic Wound Healing through Orchestrating Immunoinflammatory Microenvironment

“…42 Previous studies also have indicated that the anti-inflammatory ability of LL-37 prevents exaggerated response to damage the infected tissues, since LL-37 also enhances the acute protective activation of innate immune system to promote the early control and clearance of infection through leukocyte recruitment and chemokines production (IL-1β, GRO-α, and IL-8). 43,44 The capacity that LL-37 helps to orchestrate the immune response to infection is essential for the diabetic wound healing. In this study, the delivery of LL-37 in the PACDFe@LL-37 hydrogel system could markedly induce macrophage polarization toward the M2 phenotype, inhibit pro-inflammatory cytokines, and provide a local anti-inflammatory microenvironment for wound healing.…”

Electrospinning Nanofibers as a Dressing to Treat Diabetic Wounds

“…In a study by John et al, a PLGA/GEL fiber aerogel containing the LL-37-mimic peptide W379 enhanced proliferation and migration of keratinocytes and fibroblasts, while the introduction of macrochannels within the aerogel improved cell penetration. Moreover, the patterned macrochannels together with the incorporation of W379 greatly increased the healing time of diabetic wounds through re-epithelization by upregulating p38 mitogen-activated protein kinase expression [48]. Membranes from living cells have attracted attention as a new way of improving the bioactivity of living materials.…”