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Peer-reviewedCC BY 4.0Journal of Clinical Medicine

Enhanced Effects of Riboflavin/UVA Crosslinking, N-Acetylcysteine, and Polydatin on Collagenase Resistance in Human Corneal and Scleral Tissue: A Pilot Ex Vivo Study

8 affiliations
  1. 1Department of Medicine and Surgery, University Kore of Enna, 94100 Enna, Italy
  2. 2Siena Crosslinking Center, Monteriggioni, 53035 Siena, Italy
  3. 3University Hospitals Sussex NHS Foundation Trust, Brighton BN2 5BE, UK
  4. 4Department of Ophthalmology, University Hospital of Udine, 33100 Udine, Italy
  5. 5Department of Medicine, Surgery and Health Sciences, University of Trieste, 34129 Trieste, Italy
  6. 6Neurovisual Science Technology (NEST), 95123 Catania, Italy
  7. 7Ophthalmology Clinic, Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98122 Messina, Italy
  8. 8Department of Medicine and Health Sciences “V. Tiberio”, University of Molise, 86100 Campobasso, Italy

Abstract

Purpose: To investigate whether N-acetylcysteine (NAC) and Polygonum cuspidatum extract enhance riboflavin/ultraviolet-A crosslinking (CXL), exploring a potential adjunctive strategy for corneal and scleral tissue stabilization. Methods: In this pilot ex vivo study, 12 human corneal buttons and 12 scleral strips were assigned to six groups: untreated controls, CXL alone, adjunctive treatment alone, and adjunctive treatment before, after, or both before and after CXL. Accelerated CXL was performed at 9 mW/cm2 for 10 min (5.4 J/cm2). Resistance to collagenase-mediated degradation and corneal protein release were evaluated. Results: CXL increased corneal degradation time from 7 ± 2 to 14 ± 2 days and scleral degradation time from 10 ± 2 to 19 ± 3 days. Combined pre- and post-CXL adjunctive treatment further prolonged resistance to 21 ± 2 days in corneas (p < 0.001) and 27 ± 3 days in sclerae (p < 0.01), compared with CXL alone. Corneal protein release decreased by 84% and 52% at days 5 and 10, respectively (both p < 0.01). Conclusions: These preliminary findings suggest that biochemical adjuncts may enhance CXL-mediated extracellular matrix stabilization, opening new perspectives for ocular wall reinforcement. This approach could support future therapeutic strategies targeting corneal weakening in keratoconus and scleral remodeling in progressive myopia, with potential extensions to refractive surgery in thin corneas. Further experimental and clinical validation is warranted.

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BibTeX
@article{mazzotta2026enhanced,
  title = {{Enhanced Effects of Riboflavin/UVA Crosslinking, N-Acetylcysteine, and Polydatin on Collagenase Resistance in Human Corneal and Scleral Tissue: A Pilot Ex Vivo Study}},
  author = {Cosimo Mazzotta and Francesco Cappellani and Mayank A. Nanavaty and Marco Zeppieri and Alessandro Avitabile and Alessandro Meduri and Giovanni Scapagnini},
  journal = {Journal of Clinical Medicine},
  year = {2026},
  month = oct,
  doi = {10.3390/jcm15207836},
  url = {https://www.mdpi.com/2077-0383/15/20/7836},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Enhanced Effects of Riboflavin/UVA Crosslinking, N-Acetylcysteine, and Polydatin on Collagenase Resistance in Human Corneal and Scleral Tissue: A Pilot Ex Vivo Study
AU  - Cosimo Mazzotta
AU  - Francesco Cappellani
AU  - Mayank A. Nanavaty
AU  - Marco Zeppieri
AU  - Alessandro Avitabile
AU  - Alessandro Meduri
AU  - Giovanni Scapagnini
PY  - 2026
DA  - 2026/10/11
JO  - Journal of Clinical Medicine
DO  - 10.3390/jcm15207836
UR  - https://www.mdpi.com/2077-0383/15/20/7836
AB  - Purpose: To investigate whether N-acetylcysteine (NAC) and Polygonum cuspidatum extract enhance riboflavin/ultraviolet-A crosslinking (CXL), exploring a potential adjunctive strategy for corneal and scleral tissue stabilization. Methods: In this pilot ex vivo study, 12 human corneal buttons and 12 scleral strips were assigned to six groups: untreated controls, CXL alone, adjunctive treatment alone, and adjunctive treatment before, after, or both before and after CXL. Accelerated CXL was performed at 9 mW/cm2 for 10 min (5.4 J/cm2). Resistance to collagenase-mediated degradation and corneal protein release were evaluated. Results: CXL increased corneal degradation time from 7 ± 2 to 14 ± 2 days and scleral degradation time from 10 ± 2 to 19 ± 3 days. Combined pre- and post-CXL adjunctive treatment further prolonged resistance to 21 ± 2 days in corneas (p < 0.001) and 27 ± 3 days in sclerae (p < 0.01), compared with CXL alone. Corneal protein release decreased by 84% and 52% at days 5 and 10, respectively (both p < 0.01). Conclusions: These preliminary findings suggest that biochemical adjuncts may enhance CXL-mediated extracellular matrix stabilization, opening new perspectives for ocular wall reinforcement. This approach could support future therapeutic strategies targeting corneal weakening in keratoconus and scleral remodeling in progressive myopia, with potential extensions to refractive surgery in thin corneas. Further experimental and clinical validation is warranted.
SN  - 2077-0383
ER  -