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ACS Nano, Aug 06 2024, | https://doi.org/10.1021/acsnano.4c02345
In Situ-Forming, Bioorthogonally Cross-linked, Nanocluster-Reinforced Hydrogel for the Regeneration of Corneal Defects
Nae-Won Kang 1, Kyeongwoo Jang 1, Euisun Song 1, Uiyoung Han 1, Youngyoon Amy Seo 1, Fang Chen 1, Thitima Wungcharoen 1, Sarah C Heilshorn 2, David Myung 1,3,4
1Department of Ophthalmology, Spencer Center for Vision Research, Byers Eye Institute, Stanford University, Palo Alto, California 94304, United States.
2Department of Materials Science and Engineering, Stanford University, Stanford, California 94305, United States.
3Department of Chemical Engineering, Stanford University, Stanford, California 94305, United States.
4VA Palo Alto HealthCare System, Palo Alto, California 94304, United States.
Corresponding Author : David Myung
Abstract
Corneal defects can lead to stromal scarring and vision loss, which is currently only treatable with a cadaveric corneal transplant. Although
in situ-forming hydrogels have been shown to foster regeneration of the cornea in the setting of stromal defects, the cross-linking, biomechanical, and compositional parameters that optimize healing have not yet been established. This, Corneal defects are also almost universally inflamed, and their rapid closure without fibrosis are critical to preserving vision. Here, an
in situ forming, bioorthogonally cross-linked, nanocluster (NC)-reinforced collagen and hyaluronic acid hydrogel (NCColHA hydrogel) with enhanced structural integrity and both pro-regenerative and anti-inflammatory effects was developed and tested within a corneal defect model
in vivo. The NCs serve as bioorthogonal nanocross-linkers, providing higher cross-linking density than polymer-based alternatives. The NCs also serve as delivery vehicles for prednisolone (PRD) and the hepatocyte growth factor (HGF). NCColHA hydrogels rapidly gel within a few minutes upon administration and exhibit robust rheological properties, excellent transparency, and negligible swelling/deswelling behavior. The hydrogel's biocompatibility and capacity to support cell growth were assessed using primary human corneal epithelial cells. Re-epithelialization on the NCColHA hydrogel was clearly observed in rabbit eyes, both
ex vivo and
in vivo, with expression of normal epithelial biomarkers, including CD44, CK12, CK14, α-SMA, Tuj-1, and ZO-1, and stratified, multilayered morphology. The applied hydrogel maintained its structural integrity for at least 14 days and remodeled into a transparent stroma by 56 days.
논문정보
- Research article
- 2024년 08월 (BRIC 등록일 2024-08-07)
- 국외 연구진
- 의약학 > 약학
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