Fabrication of Bio-Based Gelatin Sponge for Potential Use as A Functional Acellular Skin Substitute

Abstract

Gelatin possesses biological properties that resemble native skin and can potentially be fabricated as a skin substitute for full-thickness wound treatment. The native property of gelatin, whereby it is easily melted and degraded at body temperature, could prevent its biofunctionality for various applications. This study aimed to fabricate and characterise buffalo gelatin (Infanca halal certified) crosslinked with chemical type crosslinker (genipin and genipin fortified with EDC) and physicaly crosslink using the dihydrothermal (DHT) method. A porous gelatin sponge (GS) was fabricated by a freeze-drying process followed by a complete crosslinking via chemical—natural and synthetic—or physical intervention using genipin (GNP), 1-ethyl-3-(3-dimethylaminopropyl) (EDC) and dihydrothermal (DHT) methods, respectively. The physicochemical, biomechanical, cellular biocompatibility and cell-biomaterial interaction of GS towards human epidermal keratinocytes (HEK) and dermal fibroblasts (HDF) were evaluated. Results showed that GS had a uniform porous structure with pore size ranging between 60 and 200 µm with high porosity (>78.6 ± 4.1%), high wettability (<72.2 ± 7.0°), high tensile strain (>13.65 ± 1.10%) and 14 h of degradation rate. An increase in the concentration and double-crosslinking approach demonstrated an increment in the crosslinking degree, enzymatic hydrolysis resistance, thermal stability, porosity, wettability and mechanical strength. The GS can be tuned differently from the control by approaching the GS via a different crosslinking strategy. However, a decreasing trend was observed in the pore size, water retention and water absorption ability. Crosslinking with DHT resulted in large pore sizes (85–300 µm) and low water retention (236.9 ± 18.7 g/m2·day) and a comparable swelling ratio with the control (89.6 ± 7.1%). Moreover no changes in the chemical content and amorphous phase identification were observed. The HEK and HDF revealed slight toxicity with double crosslinking. HEK and HDF attachment and proliferation remain similar to each crosslinking approach. Immunogenicity was observed to be higher in the double-crosslinking compared to the single-crosslinking intervention. The fabricated GS demonstrated a dynamic potential to be tailored according to wound types by manipulating the crosslinking intervention.

Characterisation of Rapid In Situ Forming Gelipin Hydrogel for Future Use in Irregular Deep Cutaneous Wound Healing

“…An X-ray diffractogram has shown a broad peak for both NC_GH and GNP_GH which indicated their amorphous nature characteristic [ 58 ]. Those findings suggested that GNP modification did not significantly alter gelatin’s natural conformation and was consistent with previous results that have been demonstrated by Arif et al [ 55 ].…”

“…Nevertheless, GH is usually featured by low gel strength without any modifications [ 48 , 52 ]. Hence, GNP crosslinking is an essential approach to improve the mechanical strength by creating an intermolecular bridge between gelatin molecules through the covalent bond [ 24 , 55 ]. Thus, they also have demonstrated reasonable resilient and adhesive force properties.…”

Wound Healing with Electrical Stimulation Technologies: A Review

“…In pressure ulcers, amazing recovery was seen in HVMPC [84][85][86]103]. The outcome of ES was comparable to the negative pressure wound therapy (NPWT) in a study of pressure ulcers [104].…”

Synergistic Effect of Biomaterial and Stem Cell for Skin Tissue Engineering in Cutaneous Wound Healing: A Concise Review

“…Gelatin is a partially hydrolyzed version of collagen and retains most collagen chemical functionality [ 78 ]. It is composed of triple amino acids of glycine proline and hydroxyproline and has been added to various biomaterials to enhance cell scaffold interactions through its Arginine-Glycine-Aspartic acid sequences, which are easily recognized by integrin receptors of cell membranes [ 81 ]. Gelatin nanofibers, along with several scaffolds like gelatin alginate sponges, gelatin-containing EGF, and gelatin films, showed possible applications in the treatment of burnt skin healing and regeneration [ 78 ].…”