Department of Fibre and Polymer Technology, KTH Royal Institute of Technology, Teknikringen 56-68, 100 44 Stockholm, Sweden.
J Am Chem Soc. 2024 Jun 26;146(25):17240-17249. doi: 10.1021/jacs.4c03673. Epub 2024 Jun 12.
Antibiotic-resistant pathogens have been declared by the WHO as one of the major public health threats facing humanity. For that reason, there is an urgent need for materials with inherent antibacterial activity able to replace the use of antibiotics, and in this context, hydrogels have emerged as a promising strategy. Herein, we introduce the next generation of cationic hydrogels with antibacterial activity and high versatility that can be cured on demand in less than 20 s using thiol-ene click chemistry (TEC) in aqueous conditions. The approach capitalizes on a two-component system: (i) telechelic polyester-based dendritic-linear-dendritic (DLDs) block copolymers of different generations heterofunctionalized with allyl and ammonium groups, as well as (ii) polyethylene glycol (PEG) cross-linkers functionalized with thiol groups. These hydrogels resulted in highly tunable materials where the antibacterial performance can be adjusted by modifying the cross-linking density. Off-stoichiometric hydrogels showed narrow antibacterial activity directed toward Gram-negative bacteria. The presence of pending allyls opens up many possibilities for functionalization with biologically interesting molecules. As a proof-of-concept, hydrophilic cysteamine hydrochloride as well as N-hexyl-4-mercaptobutanamide, as an example of a thiol with a hydrophobic alkyl chain, generated three-component networks. In the case of cysteamine derivatives, a broader antibacterial activity was noted than the two-component networks, inhibiting the growth of Gram-positive bacteria. Additionally, these systems presented high versatility, with storage modulus values ranging from 270 to 7024 Pa and different stability profiles ranging from 1 to 56 days in swelling experiments. Good biocompatibility toward skin cells as well as strong adhesion to multiple surfaces place these hydrogels as interesting alternatives to conventional antibiotics.
世界卫生组织已宣布,抗药性病原体是人类面临的主要公共卫生威胁之一。因此,迫切需要具有固有抗菌活性的材料来替代抗生素的使用,而在这方面,水凝胶已经成为一种很有前途的策略。在此,我们介绍了具有抗菌活性和高多功能性的下一代阳离子水凝胶,它可以在不到 20 秒的时间内使用硫醇-烯点击化学(TEC)在水相条件下按需固化。该方法利用了一个双组分系统:(i)具有不同代数的偕胺肟官能化的烯丙基和铵基的两亲性聚酯基树枝状线性树枝状(DLD)嵌段共聚物,以及(ii)具有巯基官能化的聚乙二醇(PEG)交联剂。这些水凝胶得到了高度可调的材料,其中通过改变交联密度可以调整抗菌性能。非化学计量的水凝胶表现出针对革兰氏阴性菌的窄抗菌活性。存在未反应的烯丙基为与生物上有趣的分子进行功能化提供了许多可能性。作为一个概念验证,亲水性半胱胺盐酸盐以及 N-己基-4-巯基丁酰胺,作为具有疏烷基链的硫醇的一个例子,生成了三组分网络。在半胱胺衍生物的情况下,观察到比双组分网络更广泛的抗菌活性,抑制了革兰氏阳性菌的生长。此外,这些系统具有很高的多功能性,储能模量值范围为 270 至 7024 Pa,在溶胀实验中具有不同的稳定性,从 1 至 56 天不等。对皮肤细胞具有良好的生物相容性以及对多种表面的强附着力使这些水凝胶成为传统抗生素的有趣替代品。