Oxidized hyaluronic acid/ε-polylysine/quaternized chitosan hydrogel with shear thinning injectability and self-healing properties for full-time and multipurpose wound healing

Huiyuan Zheng; Xiaofeng Zhang; Weijiang Wang; Huan Xin; Bin Yu; Lichen Wang; Huiqian Xie; Yage Zhang; Yang Song; Qingming Ma

doi:10.1016/j.ijbiomac.2024.139347

Oxidized hyaluronic acid/ε-polylysine/quaternized chitosan hydrogel with shear thinning injectability and self-healing properties for full-time and multipurpose wound healing

Int J Biol Macromol. 2025 Jan 2:293:139347. doi: 10.1016/j.ijbiomac.2024.139347. Online ahead of print.

Authors

Huiyuan Zheng¹, Xiaofeng Zhang², Weijiang Wang¹, Huan Xin¹, Bin Yu³, Lichen Wang³, Huiqian Xie⁴, Yage Zhang⁵, Yang Song⁶, Qingming Ma⁷

Affiliations

¹ School of Pharmacy, Qingdao University, Qingdao 266071, China.
² Shandong Qingdao Hospital of Integrated Traditional and Western Medicine, Qingdao 266002, China.
³ Guangdong Key Laboratory of Biomedical Measurements and Ultrasound School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, Guangdong 518055, China.
⁴ School of Letters and Science, University of California Santa Barbara, Santa Barbara, CA 93106, USA.
⁵ Guangdong Key Laboratory of Biomedical Measurements and Ultrasound School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, Guangdong 518055, China. Electronic address: zhangyage@szu.edu.cn.
⁶ State Key Laboratory of Metal Matrix Composites, School of Material Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: nanosurface@sjtu.edu.cn.
⁷ School of Pharmacy, Qingdao University, Qingdao 266071, China. Electronic address: qma@qdu.edu.cn.

PMID: 39755307
DOI: 10.1016/j.ijbiomac.2024.139347

Abstract

Complex wound closure scenarios necessitate the development of advanced wound dressings that can effectively address the challenges of filling irregularly shaped wounds and managing fatigue failures encountered in daily patient activities. To tackle these issues, we develop a multifunctional hydrogel from natural polysaccharides and polypeptides with injectability and self-healing properties for promoting full-time and multipurpose wound healing. Synthesized through dynamic Schiff base linkages between oxidized hyaluronic acid (OHA), ε-polylysine (ε-PL), and quaternized chitosan (QCS), the OHA/ε-PL/QCS hydrogel can gel rapidly within 50 s. It exhibits notable strong shear-thinning and self-healing behavior, allowing easy injection to fit various wound shapes while maintaining integrity. In rat models of liver and femoral artery injuries, the hydrogel shows significantly reduced bleeding and accelerated hemostasis. The hydrogel can enhance cell proliferation through cell migration and tube formation, stimulate angiogenesis, support collagen deposition, and reduce inflammation. Its superior biocompatibility also supports the safe encapsulation of epidermal growth factor (EGF). In infected full-thickness skin wound models, the OHA/ε-PL/QCS/EGF hydrogel achieves nearly complete wound closure within 10 days. Overall, this study highlights the outstanding therapeutic potentials of the injectable and self-healing OHA/ε-PL/QCS hydrogel as a promising solution for fulfilling the multi-purpose, sophisticated needs in complicated wound closure scenarios.

Keywords: Hydrogel; Injectability; Oxidized hyaluronic acid; Quaternized chitosan; Self-healing; Wound treatment.