A "T.E.S.T." hydrogel bioadhesive assisted by corneal cross-linking for in situ sutureless corneal repair

Meiyan Li; Ruoyan Wei; Chang Liu; Haowei Fang; Weiming Yang; Yunzhe Wang; Yiyong Xian; Kunxi Zhang; Yong He; Xingtao Zhou

doi:10.1016/j.bioactmat.2023.02.006

A "T.E.S.T." hydrogel bioadhesive assisted by corneal cross-linking for in situ sutureless corneal repair

Bioact Mater. 2023 Feb 11:25:333-346. doi: 10.1016/j.bioactmat.2023.02.006. eCollection 2023 Jul.

Authors

Meiyan Li^{1

2

3}, Ruoyan Wei^{1

2

3}, Chang Liu^{1

2

3}, Haowei Fang⁴, Weiming Yang^{1

2

3

5}, Yunzhe Wang^{1

2

3}, Yiyong Xian^{1

2

3}, Kunxi Zhang⁴, Yong He⁶, Xingtao Zhou^{1

2

3}

Affiliations

¹ Department of Ophthalmology, EYE & ENT Hospital of Fudan University Shanghai, China.
² NHC Key Laboratory of Myopia (Fudan University), Shanghai, China.
³ Shanghai Research Center of Ophthalmology and Optometry, Shanghai, China.
⁴ Department of Polymer Materials, School of Materials Science and Engineering, Shanghai University, Shanghai, China.
⁵ Department of Ophthalmology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
⁶ State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical Engineering, Zhejiang University, Hangzhou, China.

Abstract

Corneal transplantation is an effective clinical treatment for corneal diseases, which, however, is limited by donor corneas. It is of great clinical value to develop bioadhesive corneal patches with functions of "Transparency" and "Epithelium & Stroma generation", as well as "Suturelessness" and "Toughness". To simultaneously meet the "T.E.S.T." requirements, a light-curable hydrogel is designed based on methacryloylated gelatin (GelMA), Pluronic F127 diacrylate (F127DA) & Aldehyded Pluronic F127 (AF127) co-assembled bi-functional micelles and collagen type I (COL I), combined with clinically applied corneal cross-linking (CXL) technology for repairing damaged cornea. The patch formed after 5 min of ultraviolet irradiation possesses transparent, highly tough, and strongly bio-adhesive performance. Multiple cross-linking makes the patch withstand deformation near 600% and exhibit a burst pressure larger than 400 mmHg, significantly higher than normal intraocular pressure (10-21 mmHg). Besides, the slower degradation than GelMA-F127DA&AF127 hydrogel without COL I makes hydrogel patch stable on stromal beds in vivo, supporting the regrowth of corneal epithelium and stroma. The hydrogel patch can replace deep corneal stromal defects and well bio-integrate into the corneal tissue in rabbit models within 4 weeks, showing great potential in surgeries for keratoconus and other corneal diseases by combining with CXL.

Keywords: AF127, Aldehyded Pluronic F127; AS-OCT, Anterior Segment Optical Coherence Tomography; Bioadhesives; CCK-8, Cell Counting Kit-8; COL I, Collagen Type I; CXL; CXL, Corneal Cross-linking; Corneal patch; DLS, Dynamic Light Scattering; DMEM, Dulbecco's Modified Eagle's Medium; ECM, Extracellular Matrix; F127DA, Pluronic F127 diacrylate; FBS, Fetal Bovine Serum; GelMA, Methacryloylated Gelatin; H&E, Hematoxylin and Eosin; IHC, Immunohistochemistry; IOP, Intraocular Pressure; PBS, Phosphate-buffered Saline; RF, Riboﬂavin-5-phosphate; ROS, Reactive Oxygen Species; SD, Standard Deviation; Sutureless repair; TEM, Transmission Electron Microscopy; Tough hydrogel; UV, Ultraviolet; α-SMA, Alpha Smooth Muscle Actin.