Long-term goal: to develop and deliver novel fibronectin (FN)-derived, bioactive peptides as oligopeptide arrays to acute wounds and chronic skin ulcers to hasten healing Proposed goal: to develop novel FN-derived oligopeptide arrays that support optimal adult human dermal fibroblast adhesion and migration It is estimated that there are greater than 35 million cases of significant skin loss that require major therapeutic intervention in the US per year, 5 million of which become chronic ulcers. Direct cost for wound care is $9.7 billion/year or one-third of all yearly costs for skin disease. Despite rapid progressin our understanding of wound pathobiology, transformative developments in the care of acute and chronic cutaneous wounds have been elusive, partially because most tissue-engineered skin replacements contain cells, which makes quality control difficult, shelf-life under ambient conditions short, and user interface less than friendly. Here we propose the first steps in the design of a commercially viable, acellular construct to regenerate skin that would be relatively inexpensive, biocompatible, induce a biological response and pass regulatory (FDA) constraints. Previous research in our lab demonstrated that three functional fibronectin recombinant domains tethered to a hyaluronan hydrogel enhanced adult human connective tissue cell migration and excisional wound healing in a swine model. To develop a commercially viable tissue-engineered construct, recombinant domains must be replaced by small oligopeptides that: retain activity of domains;can be synthesized on large scale in a cost- effective manner;and resist enzymatic degradation. This proposal will focus on novel fibronectin cell- and growth factor-binding peptides that will be used in the context of the adhesion tri-peptide RGD and tested for their ability to support cell adhesion, spreading and motility.
Common causes of significant skin loss are trauma, especially thermal injury, and chronic ulcerations secondary to diabetes mellitus, pressure and venous stasis. Recent estimates have put the number of patients suffering from chronic ulcers at 5 million/year and the direct costs for wound care at $9.7 billion/year in the US. The purpose of this proposal is to test novel bioactive peptides for their potential as a therapy to repair and regenerate skin after acute trauma or in the setting of chronic ulcers.
