June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Bio-orthogonally Crosslinked Matrix Therapies for Corneal Defect Repair
Author Affiliations & Notes
  • David Myung
    Ophthalmology, Stanford University, Stanford, California, United States
    Ophthalmology, VA Palo Alto Health Care System, Palo Alto, California, United States
  • Fang Chen
    Ophthalmology, Stanford University, Stanford, California, United States
    Ophthalmology, VA Palo Alto Health Care System, Palo Alto, California, United States
  • Gabriella Fernandes-Cunha
    Ophthalmology, Stanford University, Stanford, California, United States
  • Peter Le
    Ophthalmology, Stanford University, Stanford, California, United States
  • Sarah Hull
    Chemical Engineering, Stanford University, Stanford, California, United States
  • Sarah Heilshorn
    Materials Science & Engineering, Stanford University, Stanford, California, United States
  • Footnotes
    Commercial Relationships   David Myung, Stanford University (P); Fang Chen, None; Gabriella Fernandes-Cunha, None; Peter Le, None; Sarah Hull, Stanford (P); Sarah Heilshorn, Stanford (P)
  • Footnotes
    Support  National Eye Institute/NIH K08 EY028176 and P30-EY026877, NIH F31 Pre-Doctoral Fellowship (S.M.H.), the Stanford SPARK Translational Research Program, Research to Prevent Blindness, Inc, the Matilda Ziegler Foundation, and the Department of Veterans Affairs (I21 RX003179)
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 947. doi:
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      David Myung, Fang Chen, Gabriella Fernandes-Cunha, Peter Le, Sarah Hull, Sarah Heilshorn; Bio-orthogonally Crosslinked Matrix Therapies for Corneal Defect Repair. Invest. Ophthalmol. Vis. Sci. 2021;62(8):947.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : There remains a major clinical need for ways to overcome the shortage of cadaveric donor tissue needed to surgically treat corneal blindness worldwide. Our goal is to engineer matrix therapy that stabilizes deep corneal wounds and promotes epithelial regeneration and stromal remodeling without the need for a catalyst, light-activation, sutures, or donor tissue.

Methods : We have developed crosslinked matrices of collagen as well as collagen and hyaluronic acid that form under ambient conditions through strain promoted azide-alkyne cycloaddition (SPAAC), a bio-orthogonal form of copper-free click chemistry, after being applied to deep corneal wounds without the need for a catalyst or light energy source. In vitro cell culture, ex vivo organ culture, and in vivo rabbit corneal keratectomy models were used to evaluate the biologic activity of the gel constructs out to 2 months post-operatively. Slit lamp exam, fluorescein staining, anterior segment optical coherence tomography, pachymetry, tonometry, and immunohistochemistry were used to evaluate the corneas post-treatment.

Results : Collagen and collagen-hyaluronic acid gels crosslinked by SPAAC form in situ within minutes when applied to deep keratectomy wounds under ambient conditions without the need for a catalyst or light energy. We found that the hydrogels could be cured under an air interface or under a bandage contact lens, and could restore the smooth outer curvature of a keratectomized cornea. SPAAC crosslinking yielded gels that support multi-layered surface epithelialization, tight junction formation, new basement membrane deposition, and normal IOP and corneal thickness, and complete matrix remodeling at 2 months.

Conclusions : Bio-orthogonally crosslinked gels form in situ on corneal wounds under ambient conditions through copper-free click chemistry without the need for an external catalyst or light energy source. The gels support surface epithelialization and stromal remodeling out to 2 months, which suggests their promise as a therapeutic matrix for suture-free reconstruction of deep corneal wounds.

This is a 2021 ARVO Annual Meeting abstract.

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