Heydari Parisa, Kharaziha Mahshid, Varshosaz Jaleh, Kharazi Anousheh Zargar, Javanmard Shaghayegh Haghjooy
Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111, Iran; Applied Physiology Research Center, Isfahan, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran.
Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111, Iran.
Biomater Adv. 2024 Apr;158:213762. doi: 10.1016/j.bioadv.2024.213762. Epub 2024 Jan 11.
Recently, insufficient angiogenesis and prolonged inflammation are crucial challenges of chronic skin wound healing. The sustained release of L-Arginine (L-Arg) and nitric oxide (NO) production can control immune responses, improve angiogenesis, enhance re-epithelialization, and accelerate wound healing. Here, we aim to improve wound healing via the controlled release of NO and L-Arg from poly (β-amino ester) (PβAE). In this regard, PβAE is functionalized with methacrylate poly-L-Arg (PAMA), and the role of PAMA content (50, 66, and 75 wt%) on the adhesive properties, L-Arg, and NO release, as well as collagen deposition, inflammatory responses, and angiogenesis, is investigated in vitro and in vivo. Results show that the PAMA/ PβAE could provide suitable adhesive strength (25 kPa) for wound healing application. In addition, increasing the PAMA content from 50 to 75 wt% results in an increased release of L-Arg (approximately 1.4-1.7 times) and enhanced NO production (approximately 2 times), promoting skin cell proliferation and migration. The in vitro studies also show that compared to PβAE hydrogel, incorporation of 66 wt% PAMA (PAMA 66 sample) reveals superior collagen I synthesis ( 3-4 times) of fibroblasts, controlled pro-inflammatory and improved anti-inflammatory cytokines secretion of macrophages, and accelerated angiogenesis (1.5-2 times). In vivo studies in a rat model with a full-thickness skin defect also demonstrate the PAMA66 sample could accelerate wound healing (98 %) and angiogenesis, compared to control (untreated wound) and Tegaderm™ commercial wound dressing. In summary, the engineered multifunctional PAMA functionalized PβAE hydrogel with desired NO and L-Arg release, and adhesive properties can potentially reprogram macrophages and accelerate skin healing for chronic wound healing.
最近，血管生成不足和炎症持续时间延长是慢性皮肤伤口愈合面临的关键挑战。L-精氨酸（L-Arg）的持续释放和一氧化氮（NO）的产生可以控制免疫反应、改善血管生成、促进再上皮化并加速伤口愈合。在此，我们旨在通过聚（β-氨基酯）（PβAE）控制释放NO和L-Arg来改善伤口愈合。在这方面，PβAE用甲基丙烯酸酯聚-L-精氨酸（PAMA）进行功能化，并研究了PAMA含量（50、66和75 wt%）对粘附性能、L-Arg和NO释放以及胶原蛋白沉积、炎症反应和血管生成的影响，进行了体外和体内实验。结果表明，PAMA/PβAE可为伤口愈合应用提供合适的粘附强度（约25 kPa）。此外，将PAMA含量从50 wt%增加到75 wt%会导致L-Arg释放增加（约1.4 - 1.7倍）和NO产生增强（约2倍），促进皮肤细胞增殖和迁移。体外研究还表明，与PβAE水凝胶相比，掺入66 wt% PAMA（PAMA 66样品）显示成纤维细胞的I型胶原蛋白合成能力更强（约3 - 4倍），巨噬细胞的促炎细胞因子分泌得到控制且抗炎细胞因子分泌得到改善，血管生成加速（约1.5 - 2倍）。在大鼠全层皮肤缺损模型中的体内研究也表明，与对照（未处理伤口）和Tegaderm™商用伤口敷料相比，PAMA66样品可加速伤口愈合（约98%）和血管生成。总之，具有所需NO和L-Arg释放以及粘附性能的工程化多功能PAMA功能化PβAE水凝胶可能会重新编程巨噬细胞并加速慢性伤口愈合的皮肤修复。
