Novel Fibronectin-derived Peptides To Support Optimal Fibroblast Adhesion, Migrat

描述（由申请人提供）：长期目标：开发并提供新型纤维连接蛋白（FN）衍生的生物活性肽作为寡肽阵列，用于急性伤口和慢性皮肤溃疡，以加速愈合。据估计，在美国，每年有超过3500万例需要重大治疗干预的严重皮肤脱落病例，其中500万例成为慢性溃疡。伤口护理的直接费用为97亿美元/年，占所有皮肤病年度费用的三分之一。尽管我们对伤口病理生物学的理解进展迅速，但急慢性皮肤伤口护理的变革发展一直难以捉摸，部分原因是大多数组织工程皮肤替代品含有细胞，这使得质量控制困难，环境条件下的保质期短，用户界面不够友好。在这里，我们提出了设计一种商业上可行的无细胞结构来再生皮肤的第一步，这种结构相对便宜，具有生物相容性，诱导生物反应并通过监管（FDA）的限制。我们实验室之前的研究表明，在猪模型中，三个功能性纤维连接蛋白重组结构域与透明质酸水凝胶结合可以增强成人结缔组织细胞迁移和切除伤口愈合。为了开发商业上可行的组织工程结构，重组结构域必须被小的寡肽取代：保留结构域的活性；可大规模合成，成本效益高；并且抵抗酶降解。该提案将重点关注新型纤维连接蛋白细胞和生长因子结合肽，这些肽将用于粘附三肽RGD，并测试其支持细胞粘附、扩散和运动的能力。

DESCRIPTION (provided by applicant): 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.