Bone morphogenetic protein 4 thermosensitive hydrogel inhibits corneal neovascularization by repairing corneal epithelial apical junctional complexes

Weijin Nan; Sitong Shen; Yongyan Yang; Meiliang Wu; Yuxi He; Ruiting Zhang; Xuejun Cui; Yan Zhang

doi:10.1016/j.mtbio.2024.100944

Bone morphogenetic protein 4 thermosensitive hydrogel inhibits corneal neovascularization by repairing corneal epithelial apical junctional complexes

Mater Today Bio. 2024 Jan 4:24:100944. doi: 10.1016/j.mtbio.2024.100944. eCollection 2024 Feb.

Authors

Weijin Nan^{1

2}, Sitong Shen², Yongyan Yang³, Meiliang Wu², Yuxi He², Ruiting Zhang³, Xuejun Cui^{3

4}, Yan Zhang^{1

2}

Affiliations

¹ Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Eye Diseases, Shanghai, 200080, PR China.
² Department of Ophthalmology, The Second Hospital of Jilin University, 218 Ziqiang Street, Nanguan District, Changchun, Jilin Province, 130041, PR China.
³ College of Chemistry, Jilin University, Changchun, 130012, PR China.
⁴ Weihai Institute for Bionics-Jilin University, Weihai, 264400, PR China.

Abstract

Corneal neovascularization (CNV) is a heavy attribute of blinding disease changes. Existing medications need numerous infusions and have a limited absorption. Investigating novel drugs with safety, efficacy, and convenience is crucial. In this study, we developed a bone morphogenetic protein 4 (BMP4)-loaded poloxamer-oxidized sodium alginate (F127-OSA) thermosensitive hydrogel. The 14 % F127-OSA hydrogel transformed from sol to gel at 31-32 °C, which might extend the application period on the ocular surface. The hydrogel's porous structure and uniform dispersion made it possible for drugs to release gradually. We used a suture-induced rat CNV model to investigate the mechanism of CNV inhibition by hydrogel. We discovered that F127-OSA hydrogel loaded with BMP4 could significantly reduce the length and area of CNV, relieve corneal edema, and stop aberrant epithelial cell proliferation. The hydrogel's efficacy was superior to that of the common solvent group. Additionally, BMP4 thermosensitive hydrogel repaired ultrastructure, including microvilli, intercellular junctions, and damaged apical junctional complexes (AJCs), suggesting a potential mechanism by which the hydrogel prevented CNV formation. In conclusion, our investigation demonstrates that F127-OSA thermosensitive hydrogel loaded with BMP4 can repair corneal epithelial AJCs and is a promising novel medication for the treatment of CNV.

Keywords: Apical junctional complexes; Bone morphogenetic protein 4; Corneal neovascularization; Oxidized sodium alginate; Poloxamer; Thermosensitive gel.