Regenerative peptide therapy to accelerate pressure ulcer healing

Abstract Adrenomedullin (ADM) and CGRP family peptides play pivotal roles in regulating angiogenesis, vasculogenesis, and tissue regeneration. Although wild-type ADM and CGRP improve wound healing in a variety of injury models, they are poor drug candidates for the chronic treatment of different disorders. Our recent study of super-agonistic ADM analogs, which self-assemble to form liquid nanogels in situ, suggested these analogs are ideal candidates for mitigating tissue damage and accelerating wound healing in patients with bed sores or nonhealing pressure ulcers. Notably, the self-assembled analog gel has a 100% loading capacity and allows localized treatment via its multi-faceted regenerative actions. Ideally, the proposed analog gel therapy would be administered weekly or biweekly subcutaneously in the wound area to improve local blood circulation and accelerate wound healing. The Specific Aims of this Phase I study include identifying an ideal analog gel formulation and dose range that promotes vascular bed circulation but avoids an effect on systemic hemodynamics in aging diabetic mice (Aim 1). Once the ideal analog gel is identified, we will evaluate whether the analog gel treatment correlates with enhanced healing functions in aging mice with hindlimb ischemia injury or pressure-induced skin ulcers. We will also compare the analog gel with PDGF, the only FDA-approved growth factor for wound care, thereby completing the lead optimization process.