Cell-Laden Marine Gelatin Methacryloyl Hydrogels Enriched with Ascorbic Acid for Corneal Stroma Regeneration

富含抗坏血酸的载细胞海洋明胶甲基丙烯酰水凝胶用于角膜基质再生

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作者:Ana L Alves, Ana C Carvalho, Inês Machado, Gabriela S Diogo, Emanuel M Fernandes, Vânia I B Castro, Ricardo A Pires, José A Vázquez, Ricardo I Pérez-Martín, Miguel Alaminos, Rui L Reis, Tiago H Silva

Abstract

Corneal pathologies from infectious or noninfectious origin have a significant impact on the daily lives of millions of people worldwide. Despite the risk of organ rejection or infection, corneal transplantation is currently the only effective treatment. Finding safe and innovative strategies is the main goal of tissue-engineering-based approaches. In this study, the potential of gelatin methacryloyl (GelMA) hydrogels produced from marine-derived gelatin and loaded with ascorbic acid (as an enhancer of the biological activity of cells) was evaluated for corneal stromal applications. Marine GelMA was synthesized with a methacrylation degree of 75%, enabling effective photocrosslinking, and hydrogels with or without ascorbic acid were produced, encompassing human keratocytes. All the produced formulations exhibited excellent optical and swelling properties with easy handling as well as structural stability and adequate degradation rates that may allow proper extracellular matrix remodeling by corneal stromal cells. Formulations loaded with 0.5 mg/mL of ascorbic acid enhanced the biological performance of keratocytes and induced collagen production. These results suggest that, in addition to marine-derived gelatin being suitable for the synthesis of GelMA, the hydrogels produced are promising biomaterials for corneal regeneration applications.

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