Genipin-Crosslinking Effects on Biomatrix Development for Cutaneous Wound Healing: A Concise Review

Abstract

Split skin graft (SSG), a standard gold treatment for wound healing, has numerous limitations such as lack of fresh skin to be applied, tedious process, severe scarring, and keloid formation followed by higher risks of infection. Thus, there is a gap in producing polymeric scaffolds as an alternative for wound care management. Bioscaffold is the main component in tissue engineering technology that provides porous three-dimensional (3D) microarchitecture for cells to survive. Upon skin tissue reconstruction, the 3D-porous structure ensures sufficient nutrients and gaseous diffusion and cell penetration that improves cell proliferation and vascularization for tissue regeneration. Hence, it is highly considered a promising candidate for various skin wound healing applications. To date, natural-based crosslinking agents have been extensively used to tailor the physicochemical and mechanical properties of the skin biomatrix. Genipin (GNP) is preferable to other plant-based crosslinkers due to its biological activities, such as antiinflammatory and antioxidant, which are key players to boost skin wound healing. In addition, it has shown a noncytotoxic effect and is biocompatible with human skin cells. This review validated the effects of GNP in biomatrix fabrication for skin wound healing from the last 7 years of established research articles and stipulated the biomaterial development-scale point of view. Lastly, the possible role of GNP in the skin wound healing cascade is also discussed. Through the literature output, it can be concluded that GNP has the capability to increase the stability of biomatrix and maintain the skin cells viability, which will contribute in accelerating wound healing.

Keywords: antioxidants; biomatrix; crosslinking; genipin; skin tissue engineering; wound healing.

FIGURE 1

Wound healing performance. The closure of wound occurs in four overlap steps: hemostasis, inflammation, proliferation, and remodeling.

FIGURE 2

Chronic wound. In the late-healing wound, there are excessive levels of bacteria, cytokines, and free radicals.

FIGURE 3

Type of crosslinking approaches. Generally, there are four categories of crosslinking methods: physical, chemical, enzymatical, and natural.

FIGURE 4

GNP production through geniposide hydrolysis. Crosslinking reaction between GNP and polymers leads to the formation of dark blue pigments.

FIGURE 5

Functions of GNP in scaffold fabrication. The addition of GNP into the scaffolds will produce porous scaffolds with superior mechanical strength that causes shape-retaining scaffolds.

FIGURE 6

Mechanism of the crosslinking reaction. GNP will bind to the amine groups from polymer chains and then act as a polymer connector. The connection bridge between two polymer chains will lead to stability improvement.

FIGURE 7

No toxicity of GNP-crosslinked scaffolds. Several studies have proven the survival of human skin cells in the culture during GNP-crosslinked intervention.

FIGURE 8

Effects of GNP in cytokine secretion. GNP decreased the production of cytokines which represented its antiinflammatory activity. This figure is reproduced from Szymanski et al. (2020).

FIGURE 9

GNP-crosslinked scaffolds as an alternative treatment for skin wounds. Antiinflammatory and antioxidant properties from GNP will accelerate the healing process.