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一种用于预防黑色素瘤复发和感染性伤口管理的具有募集树突状细胞功能的抗菌血液凝胶

A dendritic cell-recruiting, antimicrobial blood clot hydrogel for melanoma recurrence prevention and infected wound management.

机构信息

Department of Dermatology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, People's Republic of China; School of Pharmacy, Henan University, Kaifeng, 475004, People's Republic of China.

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai, 200433, People's Republic of China.

出版信息

Biomaterials. 2025 Feb;313:122776. doi: 10.1016/j.biomaterials.2024.122776. Epub 2024 Aug 30.

DOI:10.1016/j.biomaterials.2024.122776
PMID:39236629
Abstract

Surgical resection, the mainstay for melanoma treatment, faces challenges due to high tumor recurrence rates and complex postoperative wound healing. Chronic inflammation from residual disease and the risk of secondary infections impede healing. We introduce an innovative, injectable hydrogel system that integrates a multifaceted therapeutic approach. The hydrogel, crosslinked by calcium ions with sodium alginate, encapsulates a blood clot rich in dendritic cells (DCs) chemoattractants and melanoma cell-derived nanovesicles (NVs), functioning as a potent immunostimulant. This in situ recruitment strategy overcomes the limitations of subcutaneous tumor vaccine injections and more effectively achieves antitumor immunity. Additionally, the hydrogel incorporates Chlorella extracts, enhancing its antimicrobial properties to prevent wound infections and promote healing. One of the key findings of our research is the dual functionality of Chlorella extracts; they not only expedite the healing process of infected wounds but also increase the hydrogel's ability to stimulate an antitumor immune response. Given the patient-specific nature of the blood clot and NVs, our hydrogel system offers customizable solutions for individual postoperative requirements. This personalized approach is highlighted by our study, which demonstrates the synergistic impact of the composite hydrogel on preventing melanoma recurrence and hastening wound healing, potentially transforming postsurgical melanoma management.

摘要

手术切除是治疗黑色素瘤的主要方法,但由于肿瘤复发率高和术后伤口愈合复杂等问题,面临挑战。残留疾病引起的慢性炎症和二次感染的风险阻碍了愈合。我们引入了一种创新的、可注射的水凝胶系统,该系统集成了一种多方面的治疗方法。该水凝胶由钙离子交联的海藻酸钠交联而成,封装了富含树突状细胞(DCs)趋化因子和黑色素瘤细胞衍生的纳米囊泡(NVs)的血凝块,作为一种有效的免疫刺激剂。这种原位招募策略克服了皮下肿瘤疫苗注射的局限性,更有效地实现了抗肿瘤免疫。此外,水凝胶中还包含了小球藻提取物,增强了其抗菌性能,以防止伤口感染并促进愈合。我们研究的一个关键发现是小球藻提取物的双重功能;它们不仅加速了感染伤口的愈合过程,还提高了水凝胶刺激抗肿瘤免疫反应的能力。鉴于血凝块和 NVs 的患者特异性,我们的水凝胶系统为每个患者的术后需求提供了定制化的解决方案。我们的研究强调了这种个性化方法的重要性,该研究表明复合水凝胶在预防黑色素瘤复发和加速伤口愈合方面具有协同作用,可能会改变黑色素瘤术后的管理方式。

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