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用于持续药物递送和促进伤口愈合的去细胞外基质衍生湿粘合剂的开发。

Development of a decellularized extracellular matrix-derived wet adhesive for sustained drug delivery and enhanced wound healing.

作者信息

Wang Xinming, Zhang Haonan, Xie Weichang, Qian Bei, Huang Shixing, Zhao Qiang, Ye Xiaofeng

机构信息

Department of Cardiovascular Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

出版信息

Mater Today Bio. 2025 Apr 5;32:101734. doi: 10.1016/j.mtbio.2025.101734. eCollection 2025 Jun.

Abstract

Complete tissue recovery following traumatic injury remains a major clinical challenge. While tissue adhesives show promise for managing traumatic injuries, developing materials with robust wet adhesion and high biocompatibility remains difficult. Decellularized extracellular matrix (ECM)-derived materials are widely utilized in tissue engineering due to their superior biocompatibility and bioactivity. In this study, a wet adhesive is developed by functionalizing ECM with dopamine. The resulting ECM-dopamine exhibits strong wet adhesion and excellent biocompatibility. Furthermore, ECM-dopamine can be engineered into a drug delivery platform for small agents and macromolecules. Solid lipid nanoparticles (SLNs) are incorporated into ECM-dopamine to enable sustained release of small molecules. The ECM-dopamine-SLN system ensures sustained drug release for at least one week upon adhesion to target tissues. ECM-dopamine-SLN loaded with antimicrobials accelerates wound healing and promotes angiogenesis by modulating the inflammatory response in a mouse skin excision model. Additionally, ECM-dopamine can deliver bioactive macromolecules to injured tissue. ECM-dopamine loaded with insulin-like growth factor-1 promotes skeletal muscle regeneration in a mouse volumetric muscle loss model, likely through the modulation of M2-like macrophage polarization. The dual functionality of ECM-dopamine as both a wet adhesive and a drug delivery platform offers significant potential for regenerative medicine applications.

摘要

创伤损伤后的完全组织恢复仍然是一个重大的临床挑战。虽然组织粘合剂在处理创伤损伤方面显示出前景,但开发具有强大湿粘性和高生物相容性的材料仍然很困难。脱细胞细胞外基质(ECM)衍生材料因其卓越的生物相容性和生物活性而被广泛应用于组织工程。在本研究中,通过用多巴胺对ECM进行功能化来开发一种湿粘合剂。所得的ECM-多巴胺表现出强大的湿粘性和优异的生物相容性。此外,ECM-多巴胺可以被设计成用于小分子和大分子的药物递送平台。将固体脂质纳米粒(SLNs)掺入ECM-多巴胺中以实现小分子的持续释放。ECM-多巴胺-SLN系统在粘附到靶组织后可确保药物持续释放至少一周。负载抗菌剂的ECM-多巴胺-SLN在小鼠皮肤切除模型中通过调节炎症反应来加速伤口愈合并促进血管生成。此外,ECM-多巴胺可以将生物活性大分子递送到受伤组织。负载胰岛素样生长因子-1的ECM-多巴胺在小鼠体积性肌肉损失模型中促进骨骼肌再生,可能是通过调节M2样巨噬细胞极化实现的。ECM-多巴胺作为湿粘合剂和药物递送平台的双重功能为再生医学应用提供了巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e706/12008594/f3917c4a341e/ga1.jpg

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