Injectable Alginate-Based Hydrogels Encapsulating Engineered Endothelial Extracellular Vesicles for the Treatment of Critical Limb Ischemia

IF 5.5 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Biomacromolecules Pub Date : 2024-09-12 DOI:10.1021/acs.biomac.4c00845

Fei Fang, Hanqiao Yang, Chunli Li, Jie Ren, Xinyi Lin, Jing Xie, Xiaoheng Liu

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Abstract

Critical limb ischemia (CLI) is a peripheral arterial disease resulting from chronic inflammation of vascular systems. Recent studies have shown that inhibiting macrophage inflammation has the potential to treat CLI, and extracellular vesicles (EVs) from endothelial cells can inhibit macrophage activation. However, the limited cell-targeting capabilities and rapid clearance of EVs from the injection site limit the in vivo application of the EVs. Here, we modified endothelial EVs with platelet membranes (pM/EVs) to boost the inhibition effects on macrophage inflammation and developed an injectable alginate-based collagen composite (ACC) hydrogel for localized delivery of pM/EVs (pM/EVs@ACC) for CLI treatment. We found that pM/EVs can effectively inhibit macrophage inflammation in vitro. Furthermore, pM/EVs@ACC treatment significantly promotes the recovery of limb functions, restoring the feet’ blood supply and relieving inflammation. Our findings provide compelling evidence that the pM/EVs@ACC injectable system mediating delivery of pM/EVs is a promising strategy for CLI treatment.

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可注射的藻酸盐基水凝胶包裹的工程化内皮细胞外囊泡用于治疗重度肢体缺血

严重肢体缺血（CLI）是一种由血管系统慢性炎症引起的外周动脉疾病。最近的研究表明，抑制巨噬细胞炎症有可能治疗重症肢体缺血，而来自内皮细胞的细胞外囊泡 (EV) 可以抑制巨噬细胞的活化。然而，EVs的细胞靶向能力有限，而且会从注射部位迅速清除，这限制了EVs在体内的应用。在这里，我们用血小板膜（pM/EVs）修饰了内皮细胞的EVs，以增强其抑制巨噬细胞炎症的效果，并开发了一种可注射的藻酸盐基胶原复合材料（ACC）水凝胶，用于局部递送pM/EVs（pM/EVs@ACC）以治疗CLI。我们发现，pM/EVs 在体外能有效抑制巨噬细胞的炎症反应。此外，pM/EVs@ACC 治疗能显著促进肢体功能的恢复，恢复足部血液供应并缓解炎症。我们的研究结果提供了令人信服的证据，证明pM/EVs@ACC注射系统介导的pM/EVs递送是治疗CLI的一种前景广阔的策略。

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来源期刊

Biomacromolecules 化学-高分子科学

CiteScore

10.60

自引率

4.80%

发文量

417

审稿时长

1.6 months

期刊介绍： Biomacromolecules is a leading forum for the dissemination of cutting-edge research at the interface of polymer science and biology. Submissions to Biomacromolecules should contain strong elements of innovation in terms of macromolecular design, synthesis and characterization, or in the application of polymer materials to biology and medicine. Topics covered by Biomacromolecules include, but are not exclusively limited to: sustainable polymers, polymers based on natural and renewable resources, degradable polymers, polymer conjugates, polymeric drugs, polymers in biocatalysis, biomacromolecular assembly, biomimetic polymers, polymer-biomineral hybrids, biomimetic-polymer processing, polymer recycling, bioactive polymer surfaces, original polymer design for biomedical applications such as immunotherapy, drug delivery, gene delivery, antimicrobial applications, diagnostic imaging and biosensing, polymers in tissue engineering and regenerative medicine, polymeric scaffolds and hydrogels for cell culture and delivery.