Hydrogels in Cutaneous Wound Healing: Insights into Characterization, Properties, Formulation and Therapeutic Potential

Abstract

Hydrogels are polymeric materials that possess a set of characteristics meeting various requirements of an ideal wound dressing, making them promising for wound care. These features include, among others, the ability to absorb and retain large amounts of water and the capacity to closely mimic native structures, such as the extracellular matrix, facilitating various cellular processes like proliferation and differentiation. The polymers used in hydrogel formulations exhibit a broad spectrum of properties, allowing them to be classified into two main categories: natural polymers like collagen and chitosan, and synthetic polymers such as polyurethane and polyethylene glycol. This review offers a comprehensive overview and critical analysis of the key polymers that can constitute hydrogels, beginning with a brief contextualization of the polymers. It delves into their function, origin, and chemical structure, highlighting key sources of extraction and obtaining. Additionally, this review encompasses the main intrinsic properties of these polymers and their roles in the wound healing process, accompanied, whenever available, by explanations of the underlying mechanisms of action. It also addresses limitations and describes some studies on the effectiveness of isolated polymers in promoting skin regeneration and wound healing. Subsequently, we briefly discuss some application strategies of hydrogels derived from their intrinsic potential to promote the wound healing process. This can be achieved due to their role in the stimulation of angiogenesis, for example, or through the incorporation of substances like growth factors or drugs, such as antimicrobials, imparting new properties to the hydrogels. In addition to substance incorporation, the potential of hydrogels is also related to their ability to serve as a three-dimensional matrix for cell culture, whether it involves loading cells into the hydrogel or recruiting cells to the wound site, where they proliferate on the scaffold to form new tissue. The latter strategy presupposes the incorporation of biosensors into the hydrogel for real-time monitoring of wound conditions, such as temperature and pH. Future prospects are then ultimately addressed. As far as we are aware, this manuscript represents the first comprehensive approach that brings together and critically analyzes fundamental aspects of both natural and synthetic polymers constituting hydrogels in the context of cutaneous wound healing. It will serve as a foundational point for future studies, aiming to contribute to the development of an effective and environmentally friendly dressing for wounds.

Keywords: critical analysis; critical attributes; hydrogels; natural polymers; synthetic polymers; wound healing.

Figure 1

Representation of the chemical structures of some natural polymers classified into proteins (collagen, gelatin, and silk fibroin) and polysaccharides (alginate, hyaluronic acid, cellulose, dextran, and chitosan).

Figure 2

Synthetic polymers and their respective chemical structures.

Figure 3

Representation of some of the applications of hydrogels as wound dressings: intrinsic capacity to stimulate healing; drug delivery systems or transporters of other substances; support for cell growth; real-time monitoring of the state of wounds through the incorporation of biosensors.

Figure 4

(A) Comparison of wound size over 21 days after treatment with hydrogels. (B) In vivo observation of burn wound healing over 21 days. (C) In vivo study on EGF delivery and wound healing promotion. (D) Schematic representation of EGF loaded in carboxymethyl chitosan and alginate hydrogel. (E) In vitro inhibition of S. aureus and P. aeruginosa growth after loading ciprofloxacin in SF hydrogel. (F) In vivo study on partial-thickness burns treatment with hydrogels loaded with keratinocytes and fibroblasts (* means significant difference (p < 0.05) between the groups) (G) Schematic representation of the operation of a hydrogel incorporated with poly (N-isopropyl acrylamide) stimuli-responsive particles. Adapted from: [8,109,276,277,278].