Chitosan-Based Functional Materials for Skin Wound Repair: Mechanisms and Applications

Abstract

Skin wounds not only cause physical pain for patients but also are an economic burden for society. It is necessary to seek out an efficient approach to promote skin repair. Hydrogels are considered effective wound dressings. They possess many unique properties like biocompatibility, biodegradability, high water uptake and retention etc., so that they are promising candidate materials for wound healing. Chitosan is a polymeric biomaterial obtained by the deacetylation of chitin. With the properties of easy acquisition, antibacterial and hemostatic activity, and the ability to promote skin regeneration, hydrogel-like functional wound dressings (represented by chitosan and its derivatives) have received extensive attentions for their effectiveness and mechanisms in promoting skin wound repair. In this review, we extensively discussed the mechanisms with which chitosan-based functional materials promote hemostasis, anti-inflammation, proliferation of granulation in wound repair. We also provided the latest information about the applications of such materials in wound treatment. In addition, we summarized the methods to enhance the advantages and maintain the intrinsic nature of chitosan via incorporating other chemical components, active biomolecules and other substances into the hydrogels.

Keywords: chitosan; functional materials; hydrogels; mechanisms; wound repair.

FIGURE 1

Scheme of chitosan chemical structure [cited from literature (Abd El-Hack et al., 2020)].

FIGURE 2

The work flow of the whole article.

FIGURE 3

Schematic diagram to illustrate the mechanisms of chitosan-based hydrogels to promote wound healing. Remodeling will take place by skin tissue after the “Proliferation” stage. (A) Platelet plugs composed of platelets, leukocytes, insoluble fibrin, and erythrocytes prevent bleeding at the stage of Hemostasis. Chitosan hydrogel can help to stop hemorrhaging via promoting the aggregation of platelets and erythrocytes and inhibiting the dissolution of fibrin. (B) At “Inflammation” stage, chitosan hydrogels will assist inflammatory cells like macrophages to clear bacteria and necrotic tissue from the wound. (C) Epithelial cells proliferate and migrate to form epithelial tissue to cover the wound at the stage of “Proliferation”. Chitosan hydrogel promotes the growth of granulation tissue towards filling the tissue gap. (D) The final stage, remodeling takes place to finish the whole procedure of skin repair. Chitosan-based hydrogels take effects mainly in the first three stages.

FIGURE 4

Hemostatic effect of chitosan on skin wound which occurs at the first stage of wound healing. (A) Chitosan enhances the expression of GPIIb-IIIa from platelet. And, positively charged chitosan can interact with negatively charged molecules on the activated platelets, promoting platelet aggregation. (B) Erythrocytes aggregate via the interaction between positively charged chitosan and negatively charged molecules on erythrocyte surface. And, chitosan accelerates the formation of fibrin clots by forming a 3D network to capture erythrocytes (black arrows point chitosan). (C) Chitosan plays a hemostatic role by inhibiting fibrinolysis.

FIGURE 5

Antibacterial mechanisms of chitosan against Gram-negative (A) and Gram-positive bacteria (B). (a) Electrostatic interactions between chitosan and lipopolysaccharides (or teichoic -acid) disrupt the cell membrane, enabling chitosan to penetrate further into the cell membrane. (b) Divalent cations are chelated by chitosan, decreasing the stability of the outer membrane. (c) Chitosan inside the cell can inhibit synthesis of DNA/RNA and protein, further inhibit Gram-negative bacteria proliferation. (d) High-molecular-weight chitosan deposition on the surface of Gram-negative bacteria hinders bacterial metabolism.

FIGURE 6

Schematic illustration of light-responsive smart carboxymethyl chitosan-sodium alginate hydrogel which is composed of porphyrin photosensitizer DVDMS and PLGA-encapsulated bFGF nanospheres (Mai et al., 2020).

FIGURE 7

Schematic illustration of a typical example of self-healing hydrogel. (A) Hydrogel gelation formed from the Schiff base reaction between aminos of CMC and aldehydes of DACNC. (B) Dissolution on-demand. After adding amino acid, new Schiff-base linkages were formed from the aldehyde groups of DACNC and amino groups of amino acid, which leaded to removing of the hydrogel painlessly (Huang et al., 2018).