Oxidation-mediated scaffold engineering of hyaluronic acid-based microcarriers enhances corneal stromal regeneration

Duc Dung Nguyen; Chun-Hsu Yao; Li-Jyuan Luo; Hung-Chi Chen; Yi-Jen Hsueh; David Hui-Kang Ma; Jui-Yang Lai

doi:10.1016/j.carbpol.2022.119668

Oxidation-mediated scaffold engineering of hyaluronic acid-based microcarriers enhances corneal stromal regeneration

Carbohydr Polym. 2022 Sep 15:292:119668. doi: 10.1016/j.carbpol.2022.119668. Epub 2022 May 27.

Authors

Duc Dung Nguyen¹, Chun-Hsu Yao², Li-Jyuan Luo¹, Hung-Chi Chen³, Yi-Jen Hsueh⁴, David Hui-Kang Ma⁵, Jui-Yang Lai⁶

Affiliations

¹ Graduate Institute of Biomedical Engineering, Chang Gung University, Taoyuan 33302, Taiwan.
² Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung 40402, Taiwan; Biomaterials Translational Research Center, China Medical University Hospital, Taichung 40447, Taiwan; Department of Bioinformatics and Medical Engineering, Asia University, Taichung 41354, Taiwan.
³ Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan; Center for Tissue Engineering, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan; Department of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
⁴ Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan; Center for Tissue Engineering, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan.
⁵ Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan; Center for Tissue Engineering, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan; Department of Chinese Medicine, Chang Gung University, Taoyuan 33302, Taiwan. Electronic address: davidhkma@yahoo.com.
⁶ Graduate Institute of Biomedical Engineering, Chang Gung University, Taoyuan 33302, Taiwan; Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan; Department of Materials Engineering, Ming Chi University of Technology, New Taipei City 24301, Taiwan; Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 33303, Taiwan. Electronic address: jylai@mail.cgu.edu.tw.

PMID: 35725168
DOI: 10.1016/j.carbpol.2022.119668

Abstract

The functional design of scaffolding biomaterials with potent capabilities of promoting cell adhesion and proliferation is critically important for tissue repair and regeneration. Here, we exploit the effects of oxidation level of aldehyde hyaluronic acid (oHA) on gelatin microcarriers for repairing corneal injuries. Specifically, high oxidation levels can endow the microcarrier surface with large oHA grafting amount, smooth topography, and strong stiffness, consequently formulating biocompatible scaffolding materials with superior affinities for keratocyte attachment and growth. In a rabbit model of corneal alkali burn injury, single intracorneal injection of keratocytes/functionalized microcarriers with an appropriate oxidation level could effectively reduce corneal swelling (~62-fold improvement), recover ~94% collagen production and ~89% keratocan expression, and repair disordered collagenous stromal architecture after 4 weeks. These findings on the oxidation level effects of the aldehyde polysaccharide show a great potential use in the development of advanced scaffolds for efficient tissue engineering.

Keywords: Corneal stromal regeneration; Hyaluronic acid; Injectable keratocyte scaffold; Microcarrier-based tissue engineering; Oxidation level effects.

MeSH terms

Aldehydes / metabolism
Animals
Biocompatible Materials / pharmacology
Corneal Injuries* / drug therapy
Corneal Stroma / metabolism
Hyaluronic Acid* / pharmacology
Rabbits
Regeneration
Tissue Engineering
Tissue Scaffolds

Substances

Aldehydes
Biocompatible Materials
Hyaluronic Acid