Gelatin nanofibers coated with hyaluronic acid as a mesenchymal stromal cell scaffold for corneal regeneration

Gisele Rodrigues da Silva; Euisun Song; Karen M Chen; Fan Chen; Li Jiang; Hyeonji Kim; Nae-Won Kang; David Myung

doi:10.1016/j.ijpharm.2024.125009

Gelatin nanofibers coated with hyaluronic acid as a mesenchymal stromal cell scaffold for corneal regeneration

Int J Pharm. 2024 Nov 27:125009. doi: 10.1016/j.ijpharm.2024.125009. Online ahead of print.

Authors

Gisele Rodrigues da Silva¹, Euisun Song², Karen M Chen³, Fan Chen⁴, Li Jiang⁵, Hyeonji Kim⁶, Nae-Won Kang⁷, David Myung⁸

Affiliations

¹ School of Pharmacy, Federal University of Ouro Preto, Ouro Preto, 35400-000, MG, Brazil; Byers Eye Institute, Department of Ophthalmology, at Stanford University School of Medicine, Palo Alto 94304, CA, USA. Electronic address: giselersilva@ufop.edu.br.
² Byers Eye Institute, Department of Ophthalmology, at Stanford University School of Medicine, Palo Alto 94304, CA, USA. Electronic address: esong48@stanford.edu.
³ Department of Chemical and Biomolecular Engineering, Yonsei University, 50 Yonsei-Ro, Seodaemun-Gu, Seoul 120-749, Republic of Korea. Electronic address: karenc5@stanford.edu.
⁴ Byers Eye Institute, Department of Ophthalmology, at Stanford University School of Medicine, Palo Alto 94304, CA, USA. Electronic address: fachen@stanford.edu.
⁵ Byers Eye Institute, Department of Ophthalmology, at Stanford University School of Medicine, Palo Alto 94304, CA, USA. Electronic address: jl1992@stanford.edu.
⁶ Byers Eye Institute, Department of Ophthalmology, at Stanford University School of Medicine, Palo Alto 94304, CA, USA. Electronic address: hjkim90@stanford.edu.
⁷ Byers Eye Institute, Department of Ophthalmology, at Stanford University School of Medicine, Palo Alto 94304, CA, USA. Electronic address: nwkang@stanford.edu.
⁸ Byers Eye Institute, Department of Ophthalmology, at Stanford University School of Medicine, Palo Alto 94304, CA, USA; VA Palo Alto Health Care System, Palo Alto 94304, CA, USA; Department of Chemical Engineering, Stanford University, Stanford 94305, CA, USA. Electronic address: djmyung@stanford.edu.

PMID: 39613275
DOI: 10.1016/j.ijpharm.2024.125009

Abstract

Electrospun gelatin nanofibers coated with hyaluronic acid (GelNF-HA) were synthesized as a scaffold for delivering human corneal mesenchymal stromal cells (C-MSCs) directly to deep corneal injuries. Aligned GelNFs were produced by electrospinning, crosslinked using vapor of glutaraldehyde, coated with HA, and crosslinked with EDC/NHS. The GelNF-HA was characterized by SEM, mechanical, and optical properties. It was then investigated as a substrate for C-MSC proliferation and migration in vitro and in a rabbit cornea culture model. The expression of α-smooth muscle actin (α-SMA) was determined in the ex vivo model. SEM showed that the GelNF-HA scaffold was composed of aligned GelNFs with 75 % of the fibers oriented against the same angle. It exhibited a Young's modulus of 1.66 ± 0.59 MPa and approximately 93 % transmittance of visible light. The GelNF-HA membranes supported C-MSC proliferation in vitro. In a scratch migration assay, it facilitated complete wound closure after 48 h in culture. C-MSC-laden GelNF-HA scaffolds supported corneal wound healing in an ex vivo model as well, expressing a lower percentage of stromal α-SMA compared to both the no-treatment keratectomy-only and C-MSC groups (p < 0.05). The C-MSC-supportive GelNF-HA scaffolds hold therapeutic potential for stromal regeneration in the treatment of deep corneal defects.

Keywords: Aligned nanofibers; Corneal defect; Corneal regeneration; Electrospun nanofibers; Gelatin nanofibers coated with hyaluronic acid; Mesenchymal stromal cells.