<br/>Diabetes Mellitus is a common metabolic disorder, representing a significant health problem and economic issue. Approximately 15% of diabetic patients develop chronic wounds in their lower extremities due to complicating symptoms. Wounds in diabetic patients exhibit delayed wound closure, prolonged inflammation, and are often infected with bacteria. The gold standard of treatment for chronic wounds consists of debridement of the wound, infection control, and offloading of weight. Despite these efforts, chronic wounds frequently lead to amputation, an outcome that strongly motivates the development of new treatments. One approach to address these issues is to load cells, growth factors, or other biomolecules into scaffold materials to control release kinetics and achieve treatment localization. The difficulty here is the complex interplay between delivery material, diffusing soluble agents, and loaded cells. The wound healing process consists of a sequential cascade of cell types and growth factors, and deviation from the proper sequence can adversely affect wound healing. A more attractive solution would be to create a single component hydrogel to initiate a healing response without the aforementioned complexity. We utilize a self-assembling peptide hydrogel, termed multidomain peptide (MDP). MDPs contain a core of alternating hydrophilic and hydrophobic amino acids flanked by charged amino acids. This primary sequence results in the formation of nanofibers with a bilayer of β-sheets. The addition of multivalent salts allows nanofiber elongation and cross-linking to form a viscoelastic hydrogel. MDPs have shown significant promise for tissue engineering applications due to their customizable chemical design and desirable biocompatibility. MDP hydrogels are made from amino acids, have predictable degradation in vivo, and can be easily delivered by a syringe. With compositional and structural similarity to the native extracellular matrix, MDP hydrogels are readily infiltrated by cells, vascularized, and innervated. Because of these excellent biomaterial properties, we investigate the effect of the MDP hydrogel on the healing of full-thickness dermal wounds in genetically diabetic mice. We find wound healing is substantially accelerated with the use of this MDP hydrogel compared to a buffer-only control. The work presented herein shows the MDP hydrogel supports cells present in the wound healing process and thereby accelerates the healing of diabetic wounds.

Multidomain peptide hydrogel accelerates healing of full-thickness wounds in diabetic mice

2019 Fall National Meeting

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