Antibacterial Hydrogel Adhesives based on Bifunctional Telechelic Dendritic-Linear-Dendritic Block Copolymers

Antibiotic resistant pathogens have been declared by 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 twenty seconds by using Thiolene 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) crosslinkers functionalized with thiol groups. These hydrogels resulted in highly tunable materials where the antibacterial performance can be adjusted by modifying the crosslinking density. Off-stoichiometric hydrogels showed narrow antibacterial activity directed towards 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 also 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 towards 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（WHO）已将耐药病原菌列为人类面临的主要公共健康威胁之一。有鉴于此，迫切需要具备固有抗菌活性的材料以替代抗生素的使用，在此背景下水凝胶已成为极具前景的研究策略。本文介绍了新一代兼具抗菌活性与高通用性的阳离子水凝胶，其可在水性条件下通过巯基-烯点击化学（Thiolene Click Chemistry, TEC）实现按需固化，固化时长不足二十秒。该方法采用双组分体系：其一为经烯丙基与铵基杂化功能化的、不同代数的遥爪聚酯基树枝状-线性-树枝状（Dendritic-Linear-Dendritic, DLDs）嵌段共聚物，其二为经巯基功能化的聚乙二醇（Polyethylene Glycol, PEG）交联剂。所得水凝胶为高度可调的材料，其抗菌性能可通过改变交联密度进行调控。非化学计量比水凝胶对革兰氏阴性菌（Gram-negative bacteria）展现出窄谱抗菌活性。侧链悬垂的烯丙基基团为与具有生物活性的分子进行功能化修饰提供了广阔的可能性。作为概念验证，研究选用亲水性试剂半胱胺盐酸盐，以及带有疏水烷基链的巯基试剂N-己基-4-巯基丁酰胺为例，构建了三组分网络。半胱胺衍生物体系的抗菌谱较双组分网络更广，还可抑制革兰氏阳性菌（Gram-positive bacteria）的生长。此外，该体系展现出优异的通用性，其储能模量范围为270至7024 Pa，溶胀实验中的稳定性周期为1至56天不等。该类水凝胶对皮肤细胞具备良好的生物相容性，且对多种表面具有强粘附性，使其成为替代传统抗生素的极具潜力的候选材料。