School of Biomedical Sciences, Hunan University, Changsha, 410082, China.
College of Biology, Hunan University, Changsha, 410082, China.
J Nanobiotechnology. 2022 Apr 26;20(1):201. doi: 10.1186/s12951-022-01390-0.
Chronic wounds represent a major challenge to the present healthcare system. In recent decades, many topical therapies have been investigated for the treatment of chronic wounds, including different types of wound dressings, antimicrobial agents, and cell therapy. Platelet-derived growth factor (PDGF) plays an important role in wound healing and has been approved for treatment of wounds related to diabetes mellitus. However, the high cost and short retention time of PDGF protein have limited its wide application. To overcome this challenge, we designed a PDGF-mimicking peptide by connecting PDGF epitope VRKIEIVRKK and self-assembling motif derived from β-amyloid peptide. The resultant peptide can self-assemble into a fibril-rich network and leads to supramolecular hydrogelation with good stability. The hydrophilic epitope can be exposed on the surface of nanofibrils, which might contribute to the binding and activation of PDGF receptors. The forming hydrogel is able to induce the growth and migration of vascular endothelial cells and promote the formation of vascular branches. In the full-thickness skin wounds of healthy mice, after the application of the hydrogel, the density of neovascularization marked by CD31 was greater than that in the control group on Day 3. Larger collagen deposition and a thicker epidermis were observed on Day 12. These results demonstrate that the hydrogel can stimulate collagen deposition and angiogenesis, enhance skin regeneration, and show an excellent therapeutic effect. Taken together, this work not only provides new insight into the design of bioactive peptides but also offers a promising biomaterial for wound healing.
慢性伤口是当前医疗体系面临的重大挑战。近几十年来,人们已经研究了许多局部治疗方法来治疗慢性伤口,包括不同类型的伤口敷料、抗菌剂和细胞治疗。血小板衍生生长因子 (PDGF) 在伤口愈合中起着重要作用,已被批准用于治疗与糖尿病相关的伤口。然而,PDGF 蛋白的高成本和短保留时间限制了其广泛应用。为了克服这一挑战,我们通过连接 PDGF 表位 VRKIEIVRKK 和源自β-淀粉样肽的自组装基序设计了一种 PDGF 模拟肽。所得肽可以自组装成富含纤维的网络,并导致具有良好稳定性的超分子水凝胶化。亲水性表位可以暴露在纳米纤维的表面上,这可能有助于 PDGF 受体的结合和激活。形成的水凝胶能够诱导血管内皮细胞的生长和迁移,并促进血管分支的形成。在健康小鼠的全层皮肤伤口中,水凝胶应用 3 天后,用 CD31 标记的新生血管密度大于对照组。第 12 天观察到更大的胶原蛋白沉积和更厚的表皮。这些结果表明,水凝胶可以刺激胶原蛋白沉积和血管生成,增强皮肤再生,并显示出优异的治疗效果。综上所述,这项工作不仅为生物活性肽的设计提供了新的思路,也为伤口愈合提供了一种有前途的生物材料。