Infected Diabetic Wound Regeneration Using Peptide-Modified Chiral Dressing to Target Revascularization

Abstract

Revascularization plays a critical role in the healing of diabetic wounds. Accumulation of advanced glycation end products (AGEs) and refractory multidrug resistant bacterial infection are the two major barriers to revascularization, directly leading to impaired healing of diabetic wounds. Here, an artfully designed chiral gel dressing is fabricated (named as HA-LM2-RMR), which consists of L-phenylalanine and cationic hexapeptide coassembled helical nanofibers cross-linked with hyaluronic acid via hydrogen bonding. This chiral gel possesses abundant chiral and cationic sites, not only effectively reducing AGEs via stereoselective interaction but also specifically killing multidrug resistant bacteria rather than host cells since cationic hexapeptides selectively interact with negatively charged microbial membrane. Surprisingly, the HA-LM2-RMR fibers present an attractive ability to activate sprouted angiogenesis of Human Umbilical Vein Endothelial Cells by upregulating VEGF and OPA1 expression. In comparison with clinical Prontosan Wound Gel, the HA-LM2-RMR gel presents superior healing efficiency in the infected diabetic wound with respect to angiogenesis and re-epithelialization, shortening the healing period from 21 days to 14 days. These findings for chiral wound dressing provide insights for the design and construction of diabetic wound dressings that target revascularization, which holds great potential to be utilized in tissue regenerative medicine.

Ultrasmall calcium-enriched Prussian blue nanozymes promote chronic wound healing by remodeling the wound microenvironment

“…It is well known that angiogenesis plays a key role in wound proliferation and remodeling by providing progenitor cells, oxygen and nutrients. 29 Enzyme-linked immunosorbent assay (ELISA) and immunofluorescence technologies were applied for monitoring the status of angiogenesis, respectively. It was found that the expression of VEGF was up-regulated in the CaPB NP-treated wound in comparison with that in the control group, and the level in the CaPB NP-treated group was increased by 2 times compared with that in the control group (Fig.…”

Double Cross-Linked Hydrogel Dressings Based on Triblock Copolymers Bearing Antifreezing, Antidrying, and Inherent Antibacterial Properties

“…Meanwhile, the death of bacteria after hydrogel treatment was further verified by selecting the PNVBA-4 group with the highest bacterial survival rate as the target for laser confocal dead–live staining (Figure S3). The excellent antibacterial properties of the PNVBA hydrogels stem from their positively charged cations, − which can attract negatively charged bacteria through electrostatic interactions, and combine with the cell membrane of the bacteria to destroy the integrity of the membrane. This results in the leakage of intracellular material and the inactivation of bacterial enzymes, eventually killing the bacteria .…”

Stimuli-responsive peptide hydrogels for biomedical applications

“…Xing et al designed a chiral non-covalently crosslinked hydrogel dressing (HA-LM2-RMR) composed of l-phenylalanine and cationic hexapeptide co-assembled helical nanofibers cross-linked with hyaluronic acid via hydrogen bonding. 148 This hydrogel dressing contains abundant chiral and cationic sites that can selectively interact with the negatively charged microbial membrane. Notably, HA-LM2-RMR promotes angiogenesis of human umbilical vein endothelial cells by upregulating the expression of vascular endothelial growth factor (VEGF) and optic atrophy 1 (OPA1).…”