College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China.
Laboratory Animal Center of Sichuan University, Chengdu 610041, China.
Carbohydr Polym. 2023 Nov 15;320:121238. doi: 10.1016/j.carbpol.2023.121238. Epub 2023 Jul 27.
The healing of wounds in diabetic patients is a huge challenge issue in clinical medicine due to the disordered immune. Recruiting endogenous cells to play a role in the early stage and timely reducing inflammation to promote healing in the middle or late of injuring are both prerequisites for effective treatment. Here, inspired by natural extracellular matrix, three-dimensional porous polyurethane-hyaluronic acid hybrid hydrogel scaffolds (PUHA) were prepared to repair diabetic wound through activate cell immunity by moderate foreign body reaction, provide cell adhesion growth extracellular matrix of hyaluronic acid (HA) and exhibit anti-inflammatory effect of polyurethane (PU). The interaction between PU and HA alters the compact PU hydrogel into macroporous PUHA hydrogel scaffolds with super-swelling, elastic mechanical properties, and controllable degradation, which are suitable for endogenous cells infiltration, growth and immune activation. Additionally, incorporating with RGD, PUHA hydrogel scaffolds with bioactive physicochemical features can evidently reduce the inflammation and modulate the polarization of macrophage apparently both in vitro and in vivo, mainly through downregulation of cytokine-cytokine receptor interaction genes, leading to reprogramming immune-microenvironment and rapid diabetic wound healing. This method of gathering cells initially and intervening immune-microenvironment in time provides an expected way to design biomaterials for chronic wound healing.
糖尿病患者的伤口愈合是临床医学中的一个巨大挑战，因为其免疫系统紊乱。在受伤的早期阶段，招募内源性细胞发挥作用，并及时减少炎症以促进愈合，这两者都是有效治疗的前提。在这里，受天然细胞外基质的启发，制备了三维多孔聚氨酯-透明质酸杂化水凝胶支架（PUHA），通过适度的异物反应激活细胞免疫，为细胞提供透明质酸（HA）的粘附生长细胞外基质，并展示出聚氨酯（PU）的抗炎作用，从而修复糖尿病伤口。PU 和 HA 之间的相互作用将致密的 PU 水凝胶转变为具有超大溶胀性、弹性机械性能和可控降解性的大孔 PUHA 水凝胶支架，适合内源性细胞的浸润、生长和免疫激活。此外，与 RGD 结合后，具有生物活性物理化学特性的 PUHA 水凝胶支架可以明显减少炎症，并明显调节体外和体内巨噬细胞的极化，主要是通过下调细胞因子-细胞因子受体相互作用基因，从而重新编程免疫微环境并实现糖尿病伤口的快速愈合。这种聚集细胞并及时干预免疫微环境的方法为设计用于慢性伤口愈合的生物材料提供了一种有前景的途径。
