Engineering Nanotrap Hydrogel for Immune Modulation in Wound Healing.
Engineering Nanotrap Hydrogel for Immune Modulation in Wound Healing.
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工程纳米陷阱水凝胶用于伤口愈合中的免疫调节。
DOI：
10.1002/marc.202300322
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发表时间：
2023
影响因子：
4.6
通讯作者：
Luo,Juntao
中科院分区：
文献类型：
--
作者：
Yang,Xiguang;Guo,Dandan;Ji,Xiaotian;Shi,Changying;Luo,Juntao
不平衡的免疫调节导致异常的伤口愈合过程，例如，慢性不愈合伤口或增生性瘢痕形成。因此，抑制炎症因子的溢出是维持机体免疫调节的有效途径，有助于伤口的正常愈合。TD NT在尺寸排他的生物相容性水凝胶树脂中的缀合允许局部应用以清除细胞因子。微调水凝胶树脂中的TD NT密度/价态可控制树脂溶胀，优化分子扩散，并改善细胞因子捕获，以实现有效的免疫调节。由于TD NT纳米组装的屏障降低，具有降低的TD NT密度的水凝胶允许具有更快动力学的更高蛋白质/细胞因子吸附能力。带正电荷的TD NT水凝胶表现出从脂多糖（LPS，一种有效的内毒素）引发的免疫细胞培养基中去除带负电荷的促炎细胞因子的上级效果。带负电荷的TD NT水凝胶有效地从细胞培养基中去除带正电荷的抗炎细胞因子。TD NT水凝胶可有效抑制小鼠皮下注射LPS诱导的局部炎症反应。这些结果表明工程化的TD NT水凝胶作为局部免疫调节治疗以减轻局部炎症的巨大潜在应用。
Imbalanced immune regulation leads to the abnormal wound healing process, e.g., chronic unhealing wound or hypertrophic scar formation. Thus, the attenuation of the overflowing inflammatory factors is a viable approach to maintain the homeostatic immune regulation to facilitate normal wound healing. A versatile telodendrimer (TD) nanotrap (NT) platform is developed for efficient biomolecular protein binding. The conjugation of TD NT in size‐exclusive biocompatible hydrogel resin allows for topical application for cytokine scavenging. Fine‐tuning the TD NT density/valency in hydrogel resin controls resin swelling, optimizes molecular diffusion, and improves cytokine capture for effective immune modulation. The hydrogel with reduced TD NT density allows for higher protein/cytokine adsorption capacity with faster kinetics, due to the reduced barrier of TD NT nano‐assembly. The positively charged TD NT hydrogel exhibits superior removal of negatively charged proinflammatory cytokines from the lipopolysaccharide (LPS, a potent endotoxin) primed immune cell culture medium. The negatively charged TD NT hydrogel removes positively charged anti‐inflammatory cytokines efficiently from cell culture medium. TD NT hydrogel effectively constrains the local inflammation induced by subcutaneous LPS injection in mice. These results indicate the great potential applications of the engineered TD NT hydrogel as topical immune modulatory treatments to attenuate local inflammation.