<br>工程纳米陷阱水凝胶用于伤口愈合中的免疫调节,Macromolecular Rapid Communications

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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
Macromolecular Rapid Communications ( IF 4.2 ) Pub Date : 2023-08-02 , DOI: 10.1002/marc.202300322
Xiguang Yang ₁ , Dandan Guo ₁ , Xiaotian Ji ₁ , Changying Shi ₁ , Juntao Luo _{1,

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Affiliation

免疫调节失衡会导致伤口愈合过程异常，例如伤口慢性不愈合或增生性疤痕形成。因此，减弱溢出的炎症因子是维持稳态免疫调节以促进正常伤口愈合的可行方法。开发了一种多功能末端树枝状聚合物 (TD) 纳米陷阱 (NT) 平台，用于有效的生物分子蛋白质结合。 TD NT 在尺寸专有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/价态可控制树脂膨胀、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 纳米组装势垒降低，TD NT 密度降低的水凝胶可实现更高的蛋白质/细胞因子吸附能力和更快的动力学。带正电荷的 TD NT 水凝胶能够出色地去除脂多糖（LPS，一种强效内毒素）免疫细胞培养基中带负电荷的促炎细胞因子。带负电荷的 TD NT 水凝胶可有效去除细胞培养基中带正电荷的抗炎细胞因子。 TD NT水凝胶有效抑制小鼠皮下注射LPS引起的局部炎症。这些结果表明工程 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。

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Engineering Nanotrap Hydrogel for Immune Modulation in Wound Healing

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.

更新日期：2023-08-02

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