강내원 (Stanford University)

한빛사논문

조회260

Stanford University

CV File 796 kb

Bioact. Mater., Available online 20 June 2024 | https://doi.org/10.1016/j.bioactmat.2024.05.045 Photoactivated growth factor release from bio-orthogonally crosslinked hydrogels for the regeneration of corneal defects

Nae-Won Kang ^a, Youngyoon Amy Seo ^a, Kevin J. Jackson ^a, Kyeongwoo Jang ^a, Euisun Song ^a, Uiyoung Han ^a, Fang Chen ^a, Sarah C. Heilshorn ^b, David Myung^a,c,d

^aDepartment of Ophthalmology, Byers Eye Institute at Stanford University, School of Medicine, Palo Alto, CA 94304, United States

^bDepartment of Materials Science and Engineering, Stanford University, Stanford, CA 94305, United States

^cDepartment of Chemical Engineering, Stanford University, Palo Alto, CA 94305, United States

^dVA Palo Alto HealthCare System, Palo Alto, CA 94304, United States

Corresponding author : David Myung

Abstract

In situ-forming hydrogels are an attractive option for corneal regeneration, and the delivery of growth factors from such constructs have the potential to improve re-epithelialization and stromal remodeling. However, challenges persist in controlling the release of therapeutic molecules from hydrogels. Here, an in situ-forming bio-orthogonally crosslinked hydrogel containing growth factors tethered via photocleavable linkages (PC-HACol hydrogel) was developed to accelerate corneal regeneration. Epidermal growth factor (EGF) was conjugated to the hydrogel backbone through photo-cleavable (PC) spacer arms and was released when exposed to mild intensity ultraviolet (UV) light (2-5 mW/cm², 365 nm). The PC-HACol hydrogel rapidly gelled within a few minutes when applied to corneal defects, with excellent transparency and biocompatibility. After subsequent exposure to UV irradiation, the hydrogel promoted the proliferation and migration of corneal epithelial cells in vitro. The rate of re-epithelialization was positively correlated to the frequency of irradiation, verified through ex vivo rabbit cornea organ culture studies. In an in vivo rat corneal wound healing study, the PC-HACol hydrogel exposed to UV light significantly promoted re-epithelialization, the remodeling of stromal layers, and exhibited significant anti-scarring effects, with minimal α-SMA and robust ALDH3A1 expression. Normal differentiation of the regenerated epithelia after healing was evaluated by expression of the corneal epithelial biomarker, CK12. The remodeled cornea exhibited full recovery of corneal thickness and layer number without hyperplasia of the epithelium.

논문정보

형식Research article
게재일2024년 06월 (BRIC 등록일 2024-07-19)
연구진국외 연구진
분야 의약학 > 약학

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