ROS-Eliminating Carboxymethyl Chitosan Hydrogel to Enhance Burn Wound-Healing Efficacy.

Cheng Yang,Liping Wang,Jianwen Liao,Hai Huang,Wenxin Niu,Yuhui Chen,Chengliang Yang,Wenqiang Li,Shicai Fan

doi:10.3389/fphar.2021.679580

Abstract

Overexpression of reactive oxygen species (ROS) can lead to chronic inflammation, which limits skin wound healing. Therefore, it is of great significance to develop materials that can locally control the adverse reactions caused by excessive ROS. In this research, an ROS-sensitive hydrogel with strong free radical scavenging ability was prepared by introducing the thione (Tk) group into carboxymethyl chitosan (CMCTS) hydrogel. CMCTS hydrogel was cross-linked by NH2-Tk-NH2 agent and loaded curcumin (Cur), which possessed favorable nontoxicity, water absorption, mechanical property, biodegradability, drug release behavior, the M2 phenotype, and inflammatory factor regulating the capacity of macrophages. It is worth noting that Cur@CMCTS-Tk hydrogel can significantly inhibit oxidative damage of human fibroblasts in the H2O2-induced microenvironment and protect their viability by reducing the production of intracellular ROS. In vivo, ROS-removing hydrogel effectively accelerated the process of wound healing and possessed good regenerative properties, including hair follicle formation, promotion of new blood vessel formation, and highly orderly arrangement of collagen fibers in the full-thickness skin burn defect rat model. Hence, we expect that the Cur@CMCTS-Tk hydrogel could be used for wound treatment and tissue regeneration due to the ability to scavenge excess ROS.

Highlights

Reactive oxygen species (ROS), which play vital roles in the normal metabolism and pathological process of humans, are signaling molecules, including superoxide radical (O2-), hydrogen peroxide (H2O2), and hydroxyl radical (-OH) (Privat-Maldonado et al, 2019; Yao et al, 2019)
Cur@carboxymethyl chitosan (CMCTS)-Tk and Cur@CMCTS hydrogels were synthesized via CMCTS monomers in an aqueous phase system by using Tk and Tk-c as the cross-linker, EDC/NHS as the activating agent
We developed a Cur@CMCTS-Tk composite hydrogel dressing that progressively delivers Cur to eliminate redundant reactive oxygen species (ROS) during inflammation and new tissue formation in the process of wound healing

Summary

Introduction

Reactive oxygen species (ROS), which play vital roles in the normal metabolism and pathological process of humans, are signaling molecules, including superoxide radical (O2-), hydrogen peroxide (H2O2), and hydroxyl radical (-OH) (Privat-Maldonado et al, 2019; Yao et al, 2019). Designing a novel biomaterial that can locally control the excess ROS impairing cutaneous wound recovery and accelerate the regeneration process is urgently needed (Thannickal and Fanburg, 2000; Dröge, 2002; Kietzmann, 2010). CMCTS have a unique advantage in forming hydrogel because the presence of carboxyl groups allows CMCTS to be constructed into materials via chemical cross-linking methods. It is well-known that curcumin (Cur) extracted from the rhizome of turmeric is one kind of natural polyphenols and has anti-inflammatory and antioxidant properties. Curcumin was reported to scavenge excess ROS and reduce cellular expression of pro-inflammatory cytokines (IL-6 and TNF-α) (Kasiewicz and Whitehead, 2016; Barchitta et al, 2019; Liczbinski et al, 2020; Vallée and Lecarpentier, 2020)

Methods

Results

Conclusion