Collagen membrane loaded with doxycycline through hydroxypropyl chitosan microspheres for the early reconstruction of alkali-burned cornea

Jia Liu; Yingni Xu; Yongrui Huang; Xiaomin Sun; Yuehai Peng; Wenjing Song; Jin Yuan; Li Ren

doi:10.1016/j.ijbiomac.2023.125188

Collagen membrane loaded with doxycycline through hydroxypropyl chitosan microspheres for the early reconstruction of alkali-burned cornea

Int J Biol Macromol. 2023 Jul 31:244:125188. doi: 10.1016/j.ijbiomac.2023.125188. Epub 2023 Jun 1.

Authors

Jia Liu¹, Yingni Xu¹, Yongrui Huang¹, Xiaomin Sun¹, Yuehai Peng², Wenjing Song³, Jin Yuan⁴, Li Ren⁵

Affiliations

¹ School of Materials Science and Engineering, South China University of Technology, Guangzhou 510006, China; National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006, China; Key Laboratory of Biomedical Engineering of Guangdong Province, South China University of Technology, Guangzhou 510006, China; Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, South China University of Technology, Guangzhou 510006, China; Innovation Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, China.
² National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006, China; Key Laboratory of Biomedical Engineering of Guangdong Province, South China University of Technology, Guangzhou 510006, China; Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, South China University of Technology, Guangzhou 510006, China; Innovation Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, China; School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China; Guangzhou Proud Seeing Biotechnology Co., Ltd, Guangzhou 510623, China.
³ School of Materials Science and Engineering, South China University of Technology, Guangzhou 510006, China; National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006, China; Key Laboratory of Biomedical Engineering of Guangdong Province, South China University of Technology, Guangzhou 510006, China; Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, South China University of Technology, Guangzhou 510006, China; Innovation Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, China. Electronic address: phsongwj@scut.edu.cn.
⁴ State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510623, China. Electronic address: yuanjincornea@126.com.
⁵ School of Materials Science and Engineering, South China University of Technology, Guangzhou 510006, China; National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006, China; Key Laboratory of Biomedical Engineering of Guangdong Province, South China University of Technology, Guangzhou 510006, China; Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, South China University of Technology, Guangzhou 510006, China; Innovation Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, China; Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou 510005, China. Electronic address: psliren@scut.edu.cn.

PMID: 37270120
DOI: 10.1016/j.ijbiomac.2023.125188

Abstract

Corneal alkali burn is one of the most devastating ophthalmic emergencies correlated with remarkable morbidity resulting in severe visual impairment. Appropriate intervention in the acute phase determines the eventual outcome for later corneal restoration treatment. Since the epithelium plays an essential role in inhibiting inflammation and promoting tissue repair, sustained anti-matrix metalloproteinases (MMPs) and pro-epithelialization are the prior remedies during the first week. In this study, a drug-loaded collagen membrane (Dox-HCM/Col) that could be sutured to overlay the burned cornea was developed to accelerate the early reconstruction. Doxycycline (Dox), a specific inhibitor of MMPs, was encapsulated in collagen membrane (Col) through hydroxypropyl chitosan microspheres (HCM) to develop Dox-HCM/Col, affording a preferable pro-epithelialization microenvironment and an in-situ controlled release. Results showed that loading HCM into Col prolonged the release time to 7 days, and Dox-HCM/Col could significantly suppress the expression of MMP-9 and -13 in vitro and in vivo. Furthermore, the membrane accelerated the corneal complete re-epithelialization and promoted early reconstruction within the first week. Overall, Dox-HCM/Col was a promising biomaterial membrane for treating alkali-burned cornea in the early stage, and our attempt may provide a clinically feasible method for the ocular surface reconstruction.

Keywords: Collagen membrane; Corneal alkali burn; Doxycycline.

MeSH terms

Alkalies / metabolism
Chitosan* / metabolism
Collagen / metabolism
Cornea / metabolism
Corneal Injuries* / drug therapy
Corneal Injuries* / metabolism
Doxycycline / pharmacology
Eye Burns* / chemically induced
Eye Burns* / drug therapy
Eye Burns* / metabolism
Humans
Microspheres
Vision Disorders / metabolism

Substances

Doxycycline
Chitosan
Alkalies
Collagen