Development of Biocompatible HA Hydrogels Embedded with a New Synthetic Peptide Promoting Cellular Migration for Advanced Wound Care Management

Abstract

In the past few years, there have been many efforts underway to develop effective wound healing treatments for traumatic injuries. In particular, wound‐healing peptides (WHPs) and peptide‐grafted dressings hold great promise for novel therapeutic strategies for wound management. This study reports a topical formulation of a new synthetic WHP (REGRT, REG) embedded in a hyaluronic acid (HA)‐based hydrogel dressing for the enhancement of acute excisional wound repair. The copper‐free click chemistry is utilized to form biocompatible HA hydrogels by cross‐linking dibenzocyclooctyl‐functionalized HA with 4‐arm poly(ethylene glycol) (PEG) azide. The HA hydrogels are grafted with the REG peptide, a functional derivative of erythroid differentiation regulator1, displaying potent cell motility‐stimulating ability, thus sustainably releasing physiologically active peptides for a prolonged period. Combined with the traditional wound healing benefits of HA, the HA hydrogel embedded REG (REG‐HAgel) accelerates re‐epithelialization in skin wound healing, particularly by promoting migration of fibroblasts, keratinocytes, and endothelial cells. REG‐HAgels improve not only rate, but quality of wound healing with higher collagen deposition and more microvascular formation while being nontoxic. The peptide‐grafted HA hydrogel system can be considered as a promising new wound dressing formulation strategy for the treatment of different types of wounds with combinations of various natural and synthetic WHPs.

Functional Hydrogels as Wound Dressing to Enhance Wound Healing

“…On the other hand, the strength of the repaired tissue mainly depends on the orientation of the regenerated collagen. Therefore, a large number of reports suggest that more collagen deposition ,− during the proliferative phase, and a more consistent collagen trend in the remodeling phase indicates better wound healing efficiency.…”

“…The larger material-tissue contact area makes it possible to obtain cells, tissues, RNA, exudate, and tissue specimens from larger cross-sectional area and volume, which is more conducive to the detection of some further biochemical and histological parameters. Specifically, various parameters such as wound closure rate, inflammation cell (not caused by bacteria), granulation tissue formation, re-epithelialization, collagen deposition, angiogenesis, hair follicle formation, and a series of healing-related cells ,,, and cytokines were used to evaluate the healing process of excisional wounds. Figure B shows an example of the preparation of nanocomposite adhesive conductive self-healing antibacterial anti-oxidation multifunctional hydrogel based on the enzyme-catalyzed polymerization of dopamine between hyaluronic acid grafted dopamine and GO coated dopamine.…”

Recent trends on wound management: New therapeutic choices based on polymeric carriers

“…Histological examination showed that the HA dressing accelerates re-epithelization in skin wound healing, particularly by promoting migration of fibroblasts, keratinocytes and endothelial cells. The peptide-grafted HA hydrogel system can be considered as state of the art technology for wound repair [92] .…”

Insights into the angiogenic effects of nanomaterials: mechanisms involved and potential applications

“…VEGF activates the ERK and Akt signalling pathways, leading to metalloproteinase secretion, which degrades the basement membrane. This activation and subsequent degradation are followed by cytoskeletal remodelling with F-actin polymerization and filopodia extension, allowing endothelial cells to migrate into the wound area [118].…”