Shanghai Institute for Advanced Immunochemical Studies (SIAIS), ShanghaiTech University, Shanghai 201210, China.
Shanghai Clinical Research and Trial Center, ShanghaiTech University, Shanghai 201210, China.
Int J Mol Sci. 2024 Sep 15;25(18):9948. doi: 10.3390/ijms25189948.
Severe burns are one of the most devastating injuries, in which sustained inflammation and ischemia often delay the healing process. Pro-angiogenic growth factors such as vascular endothelial growth factor (VEGF) have been widely studied for promoting wound healing. However, the short half-life and instability of VEGF limit its clinical applications. In this study, we develop a photo-crosslinked hydrogel wound dressing from methacrylate hyaluronic acid (MeHA) bonded with a pro-angiogenic prominin-1-binding peptide (PR1P). The materials were extruded in wound bed and in situ formed a wound dressing via exposure to short-time ultraviolet radiation. The study shows that the PR1P-bonded hydrogel significantly improves VEGF recruitment, tubular formation, and cell migration in vitro. Swelling, Scanning Electron Microscope, and mechanical tests indicate the peptide does not affect the overall mechanical and physical properties of the hydrogels. For in vivo studies, the PR1P-bonded hydrogel dressing enhances neovascularization and accelerates wound closure in both deep second-degree burn and full-thickness excisional wound models. The Western blot assay shows such benefits can be related to the activation of the VEGF-Akt signaling pathway. These results suggest this photo-crosslinked hydrogel dressing efficiently promotes VEGF recruitment and angiogenesis in skin regeneration, indicating its potential for clinical applications in wound healing.
严重烧伤是最具破坏性的损伤之一，其中持续的炎症和缺血常常延迟愈合过程。血管内皮生长因子（VEGF）等促血管生成生长因子已被广泛研究用于促进伤口愈合。然而，VEGF 的半衰期短和不稳定性限制了其临床应用。在这项研究中，我们开发了一种由甲丙烯酸透明质酸（MeHA）与促血管生成 Prominin-1 结合肽（PR1P）结合而成的光交联水凝胶伤口敷料。这些材料通过短时间的紫外线辐射挤出到伤口床中，并原位形成伤口敷料。研究表明，PR1P 结合的水凝胶显著提高了体外 VEGF 募集、管状形成和细胞迁移。溶胀、扫描电子显微镜和机械测试表明，该肽不会影响水凝胶的整体机械和物理性能。在体内研究中，PR1P 结合的水凝胶敷料促进了深二度烧伤和全层切除创面模型中的新生血管形成并加速了伤口闭合。Western blot 分析表明，这些益处可能与 VEGF-Akt 信号通路的激活有关。这些结果表明，这种光交联水凝胶敷料可有效促进皮肤再生中 VEGF 的募集和血管生成，表明其在伤口愈合中的临床应用潜力。
