ORIGINAL RESEARCH article
Front. Med.
Sec. Ophthalmology
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1667446
Comparison of the regenerative potential of different functionalized gelatin-based hydrogels as fillers of rabbit corneal wounds
Provisionally accepted
- 1Universidad del Pais Vasco Facultad de Medicina y Enfermeria, Leioa, Spain
- 2Instituto de Investigacion Sanitaria Bizkaia, Barakaldo, Spain
- 3Hospital Universitario Cruces, Barakaldo, Spain
- 4Instituto Clinico Quirurgico de Oftalmologia, Bilbao, Spain
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Objectives: Persistent epithelial defects (PEDs) and chronic corneal ulcers are lesions resistant to treatment for over two weeks, risking inadequate healing, reduced sensitivity, and corneal lysis or perforation. This study evaluates the regenerative potential of functionalized gelatin-based hydrogels for treating rabbit corneal wounds as a non-surgical alternative. Methods: Thirty female New Zealand white rabbits underwent anterior stromal keratectomy and were assigned to five groups: control (0.2% HA artificial tears) and four hydrogel treatment groups. Hydrogels included non-functionalized gelatin-RFP (H) and functionalized versions with infliximab (H-Ab), autologous serum (H-AS), and human amniotic membrane extracts (H-HAMe). Crosslinking was performed in situ with blue light. Corneas were evaluated at 7 and 21 days for re-epithelialization, fibrosis, and inflammation using histology, qPCR and immunohistochemistry, focusing on markers of proliferation (Ki67), differentiation (CK3), stemness (PAX6, p63, CD44), adhesion (integrin β4), and fibrosis (α-SMA). Results: All treatments supported re-epithelialization by day 7 and restored barrier function (ZO-1), with H-AS achieving the fastest closure. Expression of the adhesion marker integrin β4 improved over time across all groups. Hydrogel formulations promoted limbal activation (PAX6, CD44), with H-AS and H-HAMe showing elevated p63 expression at day 7. All hydrogels reduced fibrosis (α-SMA), though extracellular matrix organization varied. H-Ab and H-HAMe reduced inflammation (IL-1β), while H-AS showed minimal irritability. Conclusions: Functionalized gelatin-RFP hydrogels promote re-epithelialization, reduce fibrosis and inflammation, and restore ocular integrity, offering a promising solution for corneal wound repair.
Keywords: Gelatin1, Riboflavin-phosphate2, Functionalized-hydrogels3, Corneal wound healing4, Persistent Epithelial Defects5, Corneal regeneration6
Received: 20 Jul 2025; Accepted: 02 Sep 2025.
Copyright: © 2025 Romo-Valera, Etxebarria, Freire, Arluzea and Andollo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Noelia Andollo, Universidad del Pais Vasco Facultad de Medicina y Enfermeria, Leioa, Spain
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