Peptide-Modified Chitosan Hydrogels Accelerate Skin Wound Healing by Promoting Fibroblast Proliferation, Migration, and Secretion

Abstract

Skin wound healing is a complicated process that involves a variety of cells and cytokines. Fibroblasts play an important role in this process and participate in transformation into myofibroblasts, the synthesis of extracellular matrix (ECM) and fibers, and the secretion of a variety of growth factors. This study assessed the effects of peptide Ser-Ile-Lys-Val-Ala-Val (SIKVAV)--modified chitosan hydrogels on skin wound healing. We investigated the capability of peptide SIKVAV to promote cell proliferation and migration, the synthesis of collagen, and the secretion of a variety of growth factors using fibroblasts in vitro. We also treated skin wounds established in mice using peptide SIKVAV-modified chitosan hydrogels. Hematoxylin and eosin staining showed that peptide-modified chitosan hydrogels enhanced the reepithelialization of wounds compared with negative and positive controls. Masson’s trichrome staining demonstrated that more collagen fibers were deposited in the wounds treated with peptide-modified chitosan hydrogels compared with the negative and positive controls. Immunohistochemistry revealed that the peptide-modified chitosan hydrogels promoted angiogenesis in the skin wound. Taken together, these results suggest that peptide SIKVAV-modified chitosan hydrogels may be useful in wound dressing and the treatment of skin wounds.

Nanosystems for the Encapsulation of Natural Products: The Case of Chitosan Biopolymer as a Matrix

“…Chitosan can form hydrogels with no additives due to its polycationic nature and the charge density of hydrogels could be controlled by modification of the ionic strength and pH. The chitosan-based hydrogels are a promising matrix for tissue engineering and regenerative medicine [ 71 , 72 ].…”

Progress in the Development of Chitosan-Based Biomaterials for Tissue Engineering and Regenerative Medicine

“…Polycaprolactone nanofibers loaded with CS NPs containing GM-CSF also showed accelerated wound closure [51]. Modification of CS with peptides also promotes wound closure, for example, CS hydrogels made from Ser-Ile-Lys-Val-Ala-Val-chitosan macromers [52] when applied in vivo induces collagen expression, angiogenesis, expression of TGF-β1, and inhibits the expression of TNF-α, IL-1β, and IL-6 mRNA in a mouse skin wound model [53]. CS could be further modified to increase affinity for the growth factors.…”

“…In a hydrated state, CS scaffolds lack mechanical stability and therefore require extra modifications [58]. CS induces apatite deposition [59][60][61] and this phenomenon of the polymer has been used to enhance biomineralization of composite materials because CS favors calcium/phosphate ion accumulation and enhances the biomineralization potential of poly(ethylene glycol) diacrylate/CS-based hydrogel [52].…”

Hydrogels based on chitosan in tissue regeneration: How do they work? A mini review

“…that the hydrogels made of chitosan, poly(ethylene glycol) and polyvinylpyrrolidone could work as antimicrobial and scar preventive dressings. Moreover, chitosan‐based hydrogels are regarded as carriers to deliver the therapeutic drugs topically, such as vancomycin, peptide Ser‐Ile‐Lys‐Val‐Ala‐Val, melatonin, tigecycline, bFGF, and honey bee . These drugs have at least one of following functions: (1) antibacterial; (2) anti‐inflammatory; (3) angiogenesis; and (4) the promotion of fibroblast proliferation, thus, facilitating to skin repair.…”