Theranostics 2019; 9(20):5839-5853. doi:10.7150/thno.34480 This issue

Research Paper

N-acetyl cysteine-loaded graphene oxide-collagen hybrid membrane for scarless wound healing

Jialun Li1, Chuchao Zhou1, Chao Luo1, Bei Qian1, Shaokai Liu1, Yuyang Zeng1, Jinfei Hou1, Bin Deng2, Yang Sun3, Jie Yang1, Quan Yuan1, Aimei Zhong1, Jiecong Wang1, Jiaming Sun1✉, Zhenxing Wang1✉

1. Department of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
2. Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan,430022, China
3. Department of Medical Records Management and Statistics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China

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Citation:
Li J, Zhou C, Luo C, Qian B, Liu S, Zeng Y, Hou J, Deng B, Sun Y, Yang J, Yuan Q, Zhong A, Wang J, Sun J, Wang Z. N-acetyl cysteine-loaded graphene oxide-collagen hybrid membrane for scarless wound healing. Theranostics 2019; 9(20):5839-5853. doi:10.7150/thno.34480. Available from https://www.thno.org/v09p5839.htm

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Abstract

Graphic abstract

Wound dressings composed of natural polymers, such as type I collagen, possess good biocompatibility, water holding capacity, air permeability, and degradability, and can be used in wound repair. However, due to the persistent oxidative stress in the wound area, the migration and proliferation of fibroblasts might be suppressed, leading to poor healing. Thus, collagen-containing scaffolds are not suitable for accelerated wound healing. Antioxidant N-acetyl cysteine (NAC) is known to reduce the reactive oxygen species (ROS) and has been widely used in the clinic. Theoretically, the carboxyl group of NAC allows loading of graphene oxide (GO) for sustained release and may also enhance the mechanical properties of the collagen scaffold, making it a better wound-dressing material. Herein, we demonstrated an innovative approach for a potential skin-regenerating hybrid membrane using GO incorporated with collagen I and NAC (N-Col-GO) capable of continuously releasing antioxidant NAC.

Methods: The mechanical stability, water holding capacity, and biocompatibility of the N-Col-GO hybrid membrane were measured in vitro. A 20 mm rat full-skin defect model was created to evaluate the repair efficiency of the N-Col-GO hybrid membrane. The vascularization and scar-related genes in the wound area were also examined.

Results: Compared to the Col only scaffold, N-Col-GO hybrid membrane exhibited a better mechanical property, stronger water retention capacity, and slower NAC release ability, which likely promote fibroblast migration and proliferation. Treatment with the N-Col-GO hybrid membrane in the rat wound model showed complete healing 14 days after application which was 22% faster than the control group. HE and Masson staining confirmed faster collagen deposition and better epithelization, while CD31 staining revealed a noticeable increase of vascularization. Furthermore, Rt-PCR demonstrated decreased mRNA expression of profibrotic and overexpression of anti-fibrotic factors indicative of the anti-scar effect.

Conclusion: These findings suggest that N-Col-GO drug release hybrid membrane serves as a better platform for scarless skin regeneration.

Keywords: collagen, graphene oxide, reactive oxygen species, NAC, wound healing