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基于功能化壳聚糖的抗菌水凝胶密封剂,用于眼部损伤的同时感染消除和组织闭合。

Functionalized chitosan based antibacterial hydrogel sealant for simultaneous infection eradication and tissue closure in ocular injuries.

机构信息

Antimicrobial Research Laboratory, New Chemistry Unit, Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), Jakkur, Bengaluru 560064, Karnataka, India.

L V Prasad Eye Institute, Kallam Anji Reddy Campus, L V Prasad Marg, Banjara Hills, Telangana 500034, Hyderabad, India.

出版信息

Int J Biol Macromol. 2024 Jul;273(Pt 1):132838. doi: 10.1016/j.ijbiomac.2024.132838. Epub 2024 Jun 3.

Abstract

Management of infections at ocular injury often requires prolonged and high dose of antibiotic, which is associated with challenges of antibiotic resistance and bacterial biofilm formation. Tissue glues are commonly used for repairing ocular tissue defects and tissue regeneration, but they are ineffective in curing infection. There is a critical need for antibacterial ocular bio-adhesives capable of both curing infection and aiding wound closure. Herein, we present the development of an imine crosslinked N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC)‑silver chloride nanocomposites (QAm-Ag) and poly-dextran aldehyde (PDA) based bactericidal sealant (BacSeal). BacSeal exhibited potent bactericidal activity against a broad spectrum of bacteria including their planktonic and stationary phase within a short duration of 4 h. BacSeal effectively reduced biofilm-embedded MRSA and Pseudomonas aeruginosa by ∼99.99 %. In ex-vivo human cornea infection model, BacSeal displayed ∼99 % reduction of ocular infection. Furthermore, the hydrogel exhibited excellent sealing properties by maintaining ocular pressure up to 75 mm-Hg when applied to human corneal trauma. Cytotoxicity assessment and hydrogel-treated human cornea with a retained tissue structure, indicate its non-toxic nature. Collectively, BacSeal represents a promising candidate for the development of an ocular sealant that can effectively mitigate infections and may assist in tissue regeneration by sealing ocular wounds.

摘要

眼部创伤感染的管理通常需要长期和高剂量的抗生素,这与抗生素耐药性和细菌生物膜形成的挑战有关。组织胶常用于修复眼部组织缺陷和组织再生,但对感染无效。迫切需要能够治疗感染和促进伤口闭合的抗菌眼部生物黏合剂。在此,我们介绍了一种imine 交联的 N-(2-羟丙基)-3-三甲基氯化铵壳聚糖氯化物(HTCC)-氯化银纳米复合材料(QAm-Ag)和聚葡糖醛酸醛(PDA)基杀菌密封剂(BacSeal)的开发。BacSeal 在短时间内(4 小时内)对广谱细菌(包括其浮游和静止期)表现出强大的杀菌活性。BacSeal 有效地减少了生物膜嵌入的 MRSA 和铜绿假单胞菌的数量,减少了约 99.99%。在体外人角膜感染模型中,BacSeal 使眼部感染减少了约 99%。此外,当应用于人角膜创伤时,水凝胶通过将眼内压维持在 75mmHg 以上来显示出优异的密封性能。细胞毒性评估和保留组织结构的水凝胶处理人角膜表明其无毒性。总的来说,BacSeal 是一种很有前途的眼部密封剂候选物,它可以有效地减轻感染,并通过密封眼部伤口来帮助组织再生。

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