HARVARD DEPARTMENT OF OPHTHALMOLOGY
Category : Basic and Translational Research Candidate : Mohammad Mirazul Islam Poster #: B11
Chemical Crosslinker-free Pro-regenerative Corneal Implants
Mohammad Mirazul Islam , Alexandru Chivu , Dina B . AbuSamra , Amrita Saha , Sumit Chowdhuri , Bapan Pramanik , Claes H . Dohlman , Debapratim Das , Pablo Argüeso , Jaya Rajaiya , Hirak K Patra , James Chodosh
Purpose : 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 .
Methods : 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 .
Results : 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 ).
Conclusions : 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 .