Li Xia, Zhang Kai-Wen, Zhang Zheng-Yu, Wu Jun-Jie, Yuan Zheng-Dong, Yuan Feng-Lai, Chen Jinghua
Institute of Integrated Chinese and Western Medicine, The Hospital Affiliated to Jiangnan University, Wuxi, Jiangsu 214041, China.
Institute of Integrated Chinese and Western Medicine, The Hospital Affiliated to Jiangnan University, Wuxi, Jiangsu 214041, China.
Int J Biol Macromol. 2024 Dec;282(Pt 6):137525. doi: 10.1016/j.ijbiomac.2024.137525. Epub 2024 Nov 12.
Wound regeneration with integral function and cutaneous appendages remains challenging in wound dressing applications. Cellulose nanofibers (CNF) exhibit remarkable characteristics in wound dressing applications; however, their utility in the wound healing process is limited by insufficient scar inhibition and regenerative healing. Herein, inspired by fibroblast heterogeneity mediating wound healing and skin regeneration, we developed a CNF scaffold designed to block Dipeptidyl Peptidase 4 positive (DPP4) fibroblasts for regenerative healing. CNF encapsulated sitagliptin (SITA) and zinc sulfide nanoparticles (NZnS), namely CNF@SITA@NZnS, to fabricate a novel biomaterial for scar reduction and regenerative healing. The scaffold promoted scarless healing and hair follicle regeneration in rats. In vivo experiments, the wounds in the scaffold showed less skin fibrosis, a better collagen ratio and more new hair follicles. In vitro experiments showed that the scaffold material promoted scarless healing, possibly by inhibiting the secretion of extracellular matrix and fibroblast-to-myofibroblast conversion. The promotion of hair follicle regeneration by the scaffold material may be due to promotion of the migration and proliferation of human hair follicle papilla cells. RNA sequencing is performed to explore the underlying mechanisms, which can activate ECM-receptor interaction pathway in favor of the wound healing process. The inhibiting effect of CNF@SITA@NZnS scaffold on DPP4 fibroblasts can be a potential target to reduce scarring and promote skin regeneration.
在伤口敷料应用中，实现具有完整功能和皮肤附属器的伤口再生仍然具有挑战性。纤维素纳米纤维（CNF）在伤口敷料应用中表现出显著特性；然而，它们在伤口愈合过程中的效用受到疤痕抑制不足和再生愈合的限制。在此，受介导伤口愈合和皮肤再生的成纤维细胞异质性启发，我们开发了一种旨在阻断二肽基肽酶4阳性（DPP4）成纤维细胞以实现再生愈合的CNF支架。CNF包裹西他列汀（SITA）和硫化锌纳米颗粒（NZnS），即CNF@SITA@NZnS，以制备一种用于减少疤痕和再生愈合的新型生物材料。该支架促进了大鼠的无疤痕愈合和毛囊再生。在体内实验中，支架中的伤口显示出较少的皮肤纤维化、更好的胶原蛋白比例和更多的新毛囊。体外实验表明，该支架材料可能通过抑制细胞外基质的分泌和成纤维细胞向肌成纤维细胞的转化来促进无疤痕愈合。该支架材料对毛囊再生的促进作用可能归因于促进人毛囊乳头细胞的迁移和增殖。进行RNA测序以探索潜在机制，其可激活有利于伤口愈合过程的ECM-受体相互作用途径。CNF@SITA@NZnS支架对DPP4成纤维细胞的抑制作用可能是减少疤痕和促进皮肤再生的潜在靶点。
