An injectable self-healing coordinative hydrogel with antibacterial and angiogenic properties for diabetic skin wound repair

Hao Chen,Guoqing Pan,Lei Liu,Yonghai Feng,Yufei Yan,Ruoyu Cheng,Lianfu Deng,Wenguo Cui,Xin Zhao,Haokai Shen,Allison Tam,Jin Qi,Yu Shrike Zhang,Yuhui Zhang

doi:10.1038/s41427-018-0103-9

Abstract

We report here an injectable, self-healing coordinative hydrogel with antibacterial and angiogenic properties for diabetic wound regeneration. The hydrogel was prepared by coordinative cross-linking of multi-arm thiolated polyethylene glycol (SH-PEG) with silver nitrate (AgNO3). Due to the dynamic nature of Ag-S coordination bond and bacteria-killing activity of Ag+, the resultant coordinative hydrogel featured self-healing, injectable and antibacterial properties. In this study, we synchronously loaded an angiogenic drug, desferrioxamine (DFO), in the coordinative hydrogel during cross-linking. We finally obtained a multifunctional hydrogel that is manageable, resistant to mechanical irritation, antibacterial and angiogenic in vitro. Our in vivo studies further demonstrated that the injectable self-healing hydrogel could efficiently repair diabetic skin wounds with low bacteria-infection and enhance angiogenic activity. In short, besides diabetic skin wound repair, such dynamic multifunctional hydrogel scaffolds would show great promise in the regeneration of different types of exposed wounds, in particular, in situations with disturbed physiological functions, high risk of bacterial infections, and external mechanical irritation.

Highlights

1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; Introduction Diabetes can lead to nonhealing chronic ulcers over tendons, bones, and joints, and such conditions have to date led to more than 20 million patients suffering a single leg amputation
The multifunctional hydrogel was prepared by the coordinative crosslinking of multi-arm thiolated PEG with Ag+ accompanied by the loading of the angiogenic drug DFO
In vitro experiments confirmed the multifunctionality of the dynamic coordinative hydrogel, including good flexible manipulation, resistance to mechanical irritation, antibacterial properties, and angiogenic abilities

Summary

Introduction

Diabetes can lead to nonhealing chronic ulcers over tendons, bones, and joints, and such conditions have to date led to more than 20 million patients suffering a single leg amputation. The primary cause of the dreaded and chronic diabetic ulcer complication is impaired vessel formation, microvasculature formation, which is critical for the delivery of oxygen, nutrients, and growth. Another issue that adversely affects diabetic wound healing is bacterial infection. Bacterial infection is associated with the increased frequency and length of hospitalization and the risk of extreme lower limb amputation[7] It is well-known that wounds of an external origin, especially skin ulcers, are more likely to come in contact with exogenous microorganisms, increasing the probability of bacterial

Methods

Results

Conclusion