PDF(Pubmed)
Abstract：
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.
摘要：
抗生素抗性病原体已被世界卫生组织宣布为人类面临的主要公共卫生威胁之一。出于这个原因,迫切需要具有固有抗菌活性的材料能够替代抗生素的使用，在这种情况下，水凝胶已经成为一种有前途的策略。在这里，我们介绍了下一代具有抗菌活性和高通用性的阳离子水凝胶，可以在水性条件下使用硫醇-烯点击化学（TEC）在不到20s内按需固化。该方法利用了两组分系统：（i）不同世代的基于远爪聚酯的树枝状线性树枝状（DLDs）嵌段共聚物，用烯丙基和铵基进行杂官能化，以及(ii)用硫醇基团官能化的聚乙二醇(PEG)交联剂。这些水凝胶产生高度可调的材料,其中抗菌性能可以通过改变交联密度来调节。非化学计量的水凝胶显示出针对革兰氏阴性细菌的窄抗菌活性。待定烯丙基的存在为生物学上感兴趣的分子的官能化开辟了许多可能性。作为一个概念证明,亲水性半胱胺盐酸盐以及N-己基-4-巯基丁酰胺，作为具有疏水性烷基链的硫醇的例子，生成的三组分网络。在半胱胺衍生物的情况下，注意到比双组分网络更广泛的抗菌活性，抑制革兰氏阳性菌的生长。此外,这些系统具有很高的通用性，在溶胀实验中,储能模量值在270至7024Pa的范围内,并且不同的稳定性曲线在1至56天的范围内。对皮肤细胞的良好生物相容性以及对多个表面的强粘附性使这些水凝胶成为常规抗生素的有趣替代品。
