# Multi-Responsive and Antibacterial Dynamic Covalent Hydrogels Cross-Linked by Amphiphilic Copolymer Micelles

**Authors:** Yuyao Wang, Dou Jin, Zichen Huang, Fan Chen, Kun Liu, Xiacong Zhang

PMC · DOI: 10.3390/gels12010027 · 2025-12-28

## TL;DR

This paper introduces a new type of hydrogel that responds to multiple stimuli and has antibacterial properties, suitable for wound healing and drug delivery.

## Contribution

A novel dynamic covalent hydrogel platform is developed using amphiphilic copolymer micelles with tunable responsiveness and antibacterial activity.

## Key findings

- The hydrogel degrades under acidic, alkaline, glucose, or H2O2 conditions.
- The Gel showed strong antibacterial activity against S. aureus.
- The material has a porous structure that allows efficient drug encapsulation and release.

## Abstract

Dynamic covalent hydrogels exhibiting multi-responsive and antibacterial properties offer significant potential for biomedical applications, including smart wound dressings and controlled drug delivery. Herein, a series of amphiphilic quaternized copolymers (Q-C8PEG-n) with tunable quaternization degrees was synthesized from C8PEG via iodomethane addition and characterized by 1H NMR, COSY, FTIR, UV-vis spectroscopy, DLS, TEM, and zeta potential analyses, confirming successful quaternization and micelle formation. These copolymers displayed thermosensitive behavior, with cloud point temperatures increasing due to enhanced hydrophilicity. Q-C8PEG-3 micelles, incorporating diethanolamine units, were crosslinked with phenylboronic acid-grafted hyaluronic acid (HA-PBA) to yield dynamic covalent hydrogels (Gel) through reversible boronic ester bonds stabilized by B-N coordination. The Gel exhibited multi-responsiveness, undergoing degradation in acidic or alkaline conditions and exposure to glucose or H2O2. SEM confirmed a porous microstructure, enabling efficient drug encapsulation, as demonstrated by the release of Nile red (NR). In vitro antibacterial tests revealed enhanced post-quaternization efficacy, with the Gel showing strong activity against S. aureus. This micelle-crosslinked platform synergistically combines tunable stimuli-responsiveness with inherent antibacterial properties, holding promise for applications in wound healing and tissue engineering.

## Linked entities

- **Chemicals:** Nile red (PubChem CID 65182), diethanolamine (PubChem CID 8113), phenylboronic acid (PubChem CID 66827), iodomethane (PubChem CID 6328), doxorubicin (PubChem CID 31703)

## Full-text entities

- **Chemicals:** H2O2 (MESH:D006861), hyaluronic acid (MESH:D006820), iodomethane (MESH:C014055), diethanolamine (MESH:C020283), NR (MESH:C044808), phenylboronic acid (MESH:C010686), B (MESH:D001895), 1H (-), glucose (MESH:D005947)

## Figures

11 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12841037/full.md

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Source: https://tomesphere.com/paper/PMC12841037