Himatanthus bracteatus-Composed In Situ Polymerizable Hydrogel for Wound Healing

Abstract

The Himatanthus genus presents anti-inflammatory, antioxidant activities, suggesting potential wound-healing properties. This study aimed to develop and analyze the wound-healing properties of a photopolymerizable gelatin-based hydrogel (GelMA) containing an ethanolic extract of Himatanthus bracteatus in a murine model. The extract was obtained under high pressure conditions, incorporated (2%) into the GelMA (GelMA-HB), and physically characterized. The anti-inflammatory activity of the extract was assessed using a carrageenan-induced pleurisy model and the GelMA-HB scarring properties in a wound-healing assay. The extract reduced IL-1β and TNF-α levels (48.5 ± 6.7 and 64.1 ± 4.9 pg/mL) compared to the vehicle (94.4 ± 2.3 pg/mL and 106.3 ± 5.7 pg/mL; p < 0.001). GelMA-HB depicted significantly lower swelling and increased resistance to mechanical compression compared to GelMA (p < 0.05). GelMA-HB accelerated wound closure over the time course of the experiment (p < 0.05) and promoted a significantly greater peak of myofibroblast differentiation (36.1 ± 6.6 cells) and microvascular density (23.1 ± 0.7 microvessels) on day 7 in comparison to GelMA (31.9 ± 5.3 cells and 20.2 ± 0.6 microvessels) and the control (25.8 ± 4.6 cells and 17.5 ± 0.5 microvessels) (p < 0.05). In conclusion, GelMA-HB improved wound healing in rodents, probably by modulating the inflammatory response and myofibroblastic and microvascular differentiation.

UV-polymerizable methacrylated gelatin (GelMA)-based hydrogel containing tannic acids for wound healing

“…Type III collagen forms thin fibers consisting of delicate fibrils, loosely arranged showing a weak greenish and yellow-green birefringence, whereas type I collagen forms fibers of variable thickness, arranged parallel or intertwined, with golden and reddish birefringence [ 72 ]. As observed in our study, the scarce deposition of type III collagen fibrils in the earliest stages of wound healing, which are further degraded and replaced by compact bundles (with less interfibrillar spaces) of type I collagen in the later stages, has already been reported in other studies [ 12 , 21 , 66 ]. This is because thin and delicate type III collagen fibrils are initially deposited in order to provide a three-dimensional scaffold that guides endothelial migration during the early stages of granulation tissue development.…”

“…The main advantages of the system used herein are as follows: (i) it encompasses the basic components of the healing process including angiogenesis, inflammation, fibroplasia, and epithelialization and differentiation and (ii) it is highly specific and standardized, while it is easily reproducible [ 30 ]. The very same system has already been successfully used in previous studies of wound healing in rodents [ 12 , 21 , 66 ]. The improvement of the histological grading of wound healing observed in all the groups whose skin wounds were filled with the gelatin-based biomaterials (GelMA, GPG, GGA, and GEA), in comparison to unfilled wounds (CTR), is possibly related to the bioconductive properties of the hydrogel, whose 3D-polymeric structure works as a scaffold for cell adhesion, proliferation, and migration, thus facilitating the earlier formation of granulation tissue and further reconstitution of the dermal lost tissue [ 9 – 12 ].…”

“…The very same system has already been successfully used in previous studies of wound healing in rodents [ 12 , 21 , 66 ]. The improvement of the histological grading of wound healing observed in all the groups whose skin wounds were filled with the gelatin-based biomaterials (GelMA, GPG, GGA, and GEA), in comparison to unfilled wounds (CTR), is possibly related to the bioconductive properties of the hydrogel, whose 3D-polymeric structure works as a scaffold for cell adhesion, proliferation, and migration, thus facilitating the earlier formation of granulation tissue and further reconstitution of the dermal lost tissue [ 9 – 12 ]. However, since GPG and GGA presented significantly better histological gradings over the time-course of the experiment, gallic acid released into the wound bed could likely be triggering additional pathophysiological, biochemical, or molecular scarring mechanisms, in addition to those promoted by GelMA, providing even better healing outcomes.…”

“…Hydrogels based on methacrylated gelatin (GelMA) obtained by ultraviolet (UV) photoreticulation have been reported as an excellent biomaterial for wound dressings because they allow for proper cell adhesion, are highly permeable to nutrients, proteins, and oxygen, and can be easily degraded by enzymes [ 9 , 10 ]. GelMA is also reported to be an effective biopolymer to load and deliver bioactive compounds and other drugs to improve wound healing [ 11 , 12 ].…”

A Dual-Crosslinked Hydrogel Based on Gelatin Methacryloyl and Sulfhydrylated Chitosan for Promoting Wound Healing

“…Here, we report a dual-crosslinked hydrogel comprising photocrosslinkable gelatin methacryloyl (GelMA) and CS-SH for wound dressing. Recent advances indicate that GelMA-based hydrogels are a suitable platform for developing wound dressing biomaterials [20][21][22]. In this study, GelMA and CS-SH were crosslinked through both light-induced polymerization and the Thiol-ene reaction.…”