Adhesivity-tuned bioactive gelatin/gellan hybrid gels drive efficient wound healing.

Gelatin-based hydrogels have been widely used for wound healing applications. However, increase in ligand density and reduction in pore size with increasing gelatin concentration may delay wound healing by limiting cell infiltration. In this study, we address this shortcoming by combining gelatin with gellan-which is super hydrophilic and non-adhesive to cells. We show that UV crosslinked hybrid gels composed of methacrylated gelatin (GelMA) and methacrylated gellan gum (mGG), possess considerably larger pores and improved mechanical properties compared to GelMA gels. Reduced spreading and reduced formation of focal adhesions on hybrid gels combined with lower contractility and faster detachment upon trypsin-induced de-adhesion suggests that hybrid gels are less adhesive than GelMA gels. Gradual release of fibroblast growth factor (FGF) and silver nanoparticles (AgNPs) incorporated in hybrid gels not only boosts cell migration, but also confers anti-bacterial activity against gram-positive and gram-negative bacteria at concentrations nontoxic to cells. Full thickness wound healing in Wistar rats revealed increased granulation tissue formation in hybrid gels, fastest epithelialization and highest collagen deposition in rats treated with FGF entrapped hybrid gels. Together, our results demonstrate how adhesive tuning and incorporation of bioactive factors can be synergistically combined for achieving complete wound healing.

Dehydrated Human Amnion/Chorion Membrane Allografts as an Adjunct Wound Healing Therapy in Diabetic Rats.

Chronic, non-healing wounds pose a serious public health issue and the need for new treatment methods is paramount. Dehydrated human amnion/chorion membrane has potential wound healing properties, due to the enrichment of growth factors and anti-inflammatory properties. However, its auxiliary advantage on diabetic wounds with demonstrated safety and efficacy in animal models has not been extensively documented. This study aimed at evincing the wound-healing property of dehydrated human amnion chorion membrane in diabetic and non-diabetic rats. An excisional wound model was developed in 36 male Sprague-Dawley rats that were randomly classified into six groups for two experiments. The non-diabetic rat group included non-diabetic control (G1), dHACM treatment (G2), and dHACM dressing + saline-treatment (G3); (n = 6). Similarly, the diabetic group included diabetic control (G4), dHACM treatment (G5), and dHACM dressing + saline-treatment (G6); (n = 6). The results of wound contractility rate, re-epithelialization, grading of granulation tissue, and collagen deposition from histopathological observation demonstrated that in comparison with the other groups (G1, G2, G4, and G5), the animal groups treated with dHACM dressing + saline-treatment (G3 and G6) had superior regenerative effects in excisional wound model. Also, in the animals of G5 and G6 of the diabetic group, there was no statistically significant difference (P > 0.05) in the levels of glucose, urea, creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphate (ALP), when compared to G4 animals during the experiment. It is evident from this study that dHACM could be applied as a potential wound healing biomaterial, especially in diabetic conditions.

High ligand density drives extensive spreading and motility on soft GelMA gels.

In comparison to synthetic hydrogels where ligand density and stiffness can be independently tuned, cell responses are expected to deviate on native biopolymer networks where ligand density and stiffness are coupled. Here we probe the tensional homeostasis of fibroblasts on methacrylated gelatin (GelMA) gels, which are widely used in tissue engineering applications. On 5%-15% GelMA gels which are very soft (10-100's of Pa's in stiffness), fibroblasts were found to spread extensively and assemble prominent stress fibers and focal adhesions. Probing of contractile mechanics using trypsin-induced detachment revealed adhesive drag, but not contractility, was sensitive to GelMA concentration. Contractility-altering drugs blebbistatin and nocodazole, which exhibited opposite effects on focal adhesion size, both led to reduction in adhesive drag and cell rounding. However, cell motility was impacted only in nocodazole-treated cells. Collectively, our experiments suggest that on soft GelMA gels, contractility-independent adhesion clustering mediated by high ligand density can drive cell spreading and motility.