In Vivo Wound-Healing Efficacy of Insulin-Loaded Strontium-Cross-Linked Alginate-Based Hydrogels in Diabetic Rats.

The wound-healing effect of insulin is well studied and reported. However, prolonged topical application of insulin without compromising its biological activity is still a challenge. In this study, the effect of topically delivered insulin on promoting wound healing in diabetic animals was evaluated. Alginate diamine PEG-g-poly(PEGMA) (ADPM2S2) was the material used for the topical delivery of insulin. ADPM2S2 hydrogels release insulin and strontium ions, and they synergistically act to regulate different phases of wound healing. Insulin was released from the ADPM2S2 hydrogel for a period of 48 h, maintaining its structural stability and biological activity. In vitro studies were performed under high-glucose conditions to evaluate the wound-healing potential of insulin. Insulin-loaded ADPM2S2 hydrogels showed significant improvement in cell migration, proliferation, and collagen deposition, compared to control cells under high-glucose conditions. Immunostaining studies in L929 cells showed a reduction in phospho Akt expression under high-glucose conditions, and in the presence of insulin, the expression increased. The gene expression studies revealed that insulin plays an important role in regulating the inflammatory phase and macrophage polarization, which favors accelerated wound closure. In vivo experiments in diabetic rat excision wounds treated with insulin-loaded ADPM2S2 showed 95% wound closure within 14 days compared with 82% in control groups. Thus, both the in vitro and in vivo results signify the therapeutic potential of topically delivered insulin in wound management under high-glucose conditions.

Ascorbic acid-loaded gellan-g-poly(ethylene glycol) methacrylate matrix as a wound-healing material.

Ascorbic acid (AA) is one of the important biomolecules involved in all phases of wound healing. The aim of this study was to develop a new hydrogel system that offers topical delivery of ascorbic acid to wounds during wound care management. In this work, we grafted poly (ethylene glycol) methacrylate onto a renewable biopolymer gellan, and the graft copolymer (GPMA) formed was crosslinked covalently and ionically, and used as a matrix for delivering AA to the wounds. By the processes of grafting and crosslinking, the mechanical properties of the gellan increased several fold compared to mechanically weak native gellan. In vitro cytotoxicity evaluation showed that GPMA was non-cytotoxic to fibroblast cells. GPMA hydrogel matrix allowed the sustained release of AA. When AA was incorporated in GPMA, a significant improvement in wound closure was observed in scratch wound assay performed with keratinocytes. Since AA acts as a cofactor in collagen synthesis, the controlled delivery of AA to the wound microenvironment favors the up-regulation of colα1 gene expression. This study revealed that ascorbic acid, at a concentration of 150 µM, has a favorable impact on wound healing when tested in vitro. Overall results indicate that the GPMA matrix could be a promising material for wound healing applications.

Synthesis and evaluation of an alginate-methacrylate xerogel for insulin delivery towards wound healing applications.

Background: Alginate is one of the most widely used biopolymer for wound healing. But poor mechanical strength and degradability limits its application especially as a drug-delivery matrix. The aim of this study was to develop stable alginate based scaffold for insulin delivery toward wound care. Materials & methods: The xerogel alginate-g-poly (methacrylic acid; AGM2S) was characterized by various analytical techniques. Results: AGM2S xerogel showed improved physical stability, low degradation, good swelling and water vapour transmission rate (WVTR). About 70% of insulin was released from loaded xerogel over a period of 48 h and favorably modulated the healing response in in vitro scratch wound assay. Conclusion: Grafting improved the strength and stability of alginate xerogel and the results suggest the application of insulin loaded AGM2S xerogels as a potential wound healing material.