Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208.
Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
Proc Natl Acad Sci U S A. 2018 Jun 26;115(26):6816-6821. doi: 10.1073/pnas.1804262115. Epub 2018 Jun 11.
The successful treatment of chronic dermal wounds, such as diabetic foot ulcers (DFU), depends on the development of safe, effective, and affordable regenerative tools that the surgeon can rely on to promote wound closure. Although promising, strategies that involve cell-based therapies and the local release of exogenous growth factors are costly, require very long development times, and result in modest improvements in patient outcome. We describe the development of an antioxidant shape-conforming regenerative wound dressing that uses the laminin-derived dodecapeptide A5G81 as a potent tethered cell adhesion-, proliferation-, and haptokinesis-inducing ligand to locally promote wound closure. A5G81 immobilized within a thermoresponsive citrate-based hydrogel facilitates integrin-mediated spreading, migration, and proliferation of dermal and epidermal cells, resulting in faster tissue regeneration in diabetic wounds. This peptide-hydrogel system represents a paradigm shift in dermoconductive and dermoinductive strategies for treating DFU without the need for soluble biological or pharmacological factors.
慢性皮肤伤口（如糖尿病足溃疡）的成功治疗取决于安全、有效且负担得起的再生工具的开发，外科医生可以依靠这些工具来促进伤口闭合。尽管有希望，但涉及细胞疗法和局部释放外源性生长因子的策略成本高昂，需要非常长的开发时间，并且只能适度改善患者的预后。我们描述了一种抗氧化形状适应性再生伤口敷料的开发，该敷料使用层粘连蛋白衍生的十二肽 A5G81 作为一种有效的连接细胞粘附、增殖和趋化诱导配体，局部促进伤口闭合。固定在热响应性柠檬酸盐基水凝胶中的 A5G81 促进真皮和表皮细胞的整合素介导的扩散、迁移和增殖，从而使糖尿病伤口更快地组织再生。这种肽-水凝胶系统代表了治疗糖尿病足溃疡的真皮传导和真皮诱导策略的范式转变，而无需使用可溶性生物或药理因素。
