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Mohammad Mirazul Islam, Alexandru Chivu, Dina Abusamra, Sina Sharifi, Amrita Saha, Sumit Chowdhuri, Claes H. Dohlman, Debapratim Das, Pablo Argueso, Jaya Rajaiya, Hirak Patra, James Chodosh; Chemical Crosslinker-free Pro-regenerative Corneal Implants. Invest. Ophthalmol. Vis. Sci. 2022;63(7):95 – A0193.
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© ARVO (1962-2015); The Authors (2016-present)
Transplantation of the cornea is a standard procedure for the treatment of corneal blindness, but there is a severe scarcity of donor corneas. The development of an artificial cornea could help to quell the demand. Collagen-based artificial corneas, in which the collagen has been chemically crosslinked, have shown promise in human trials. However, most crosslinking agents are cytotoxic. In the absence of crosslinking, collagen implants are mechanically weak and susceptible to enzymatic degradation. In this work, we successfully fabricated transparent hydrogels as corneal substitutes from collagen, without using any crosslinkers or modifying the native collagen structure.
We developed a pyrene conjugated dipeptide amphiphile PyKC consisting of lysine and cysteine for supramolecular gelation where collagen molecules are intertwined inside the PyKC network without any alteration of the collagen. Hydrogels of 10% and 15% collagen (as controls), 10% collagen-1% PyKC, 10% collagen-2% PyKC, 15% collagen-1% PyKC, and 15% collagen-2% PyKC, are referred to as Coll10, Coll15, Coll10-PyKC1, Coll10-PyKC2, Coll15-PyKC1 and Coll15-PyKC2, respectively. We measured physicochemical properties, biocompatibility, immunogenicity and antiviral property of the hydrogels. One-way ANOVA with Tukey post hoc test was performed to compare between groups.
Light transmission studies showed the hydrogels are transparent in visible light and block UV light. The hydrogels were mechanically comparable with controls (Coll10 and Coll15-PyKC2, p=0.0555), enzymatically stable, and the tolerance for sutures was increased compared to controls (Coll10 and Coll15-PyKC2, p=0.0128). The hydrogels also supported the growth and function of corneal epithelial, stromal, and endothelial cells. In vitro immune response studies showed that the hydrogels suppressed the inflammatory differentiation of human monocyte-derived dendritic cells. The hydrogels also restricted adenovirus propagation (Coll15 and Coll15-PyKC1, p=0.0007).
Our newly developed crosslinker-free fabrication strategy may dramatically impact the development of corneal implants. The hydrogels can also be modified to encapsulate cells, drugs, growth factors, and/or antibodies for therapeutic use.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.
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