The proposed study will test the hypothesis that a hydrogel sealant can replace conventional sutures in the repair of corneal and scleral tissue. Recently, the investigators have prepared hydrogel sealants from well-defined monodisperse polymers, which are composed of biocompatible monomers called biodendrimers. Biodendrimers have several features that make them uniquely attractive for this sealant application: (1) the chemical composition, physical structure, and molecular weight can be precisely controlled; (2) the dendrimer structure permits diverse and extensive functionalization that facilitates covalent intermolecular crosslinking to form a hydrogel; (3) aqueous solutions of biodendrimer can be crosslinked in situ to form a functional and well-integrated hydrogel scaffold using a mild crosslinking reaction; and (4) the mechanical properties of crosslinked biodendrimer hydrogels can be tuned over a wide range of values by varying the functional groups, molecular weight, dendrimer structure, and concentration. ? ? Specifically, the researchers propose to engineer biodendrimer hydrogel sealants for functional in vivo repair of ocular tissue. We plan to quantify various measures of sealant functions both in vitro and in vivo as a set of outcomes for each formulation, including parameters of mechanical and biological behaviors, biochemical composition, and histological appearance.
The specific aims of this study are: (1) synthesize, crosslink, and characterize self-gelling biodendrimer sealants; (2) evaluate functional characteristics of biodendrimer sealants in vitro and in vivo for repairing 4.1 mm central corneal lacerations; (3) evaluate functional characteristics of biodendrimer sealants in vitro and in vivo for securing a corneal autograft; and (4) evaluate functional characteristics of biodendrimer sealants in vitro and in vivo for repairing scleral incisions in a vitrectomy procedure. ? ? The results from the successful completion of these proposed studies will yield a database of properties, structure-property relationships, insights to guide the design of an optimized biodendrimer-based sealant, and potentially, a general sealant for ocular tissue repair. ? ? Relevance to Public Health. The proposed study will lead to new ophthalmic surgical techniques, procedures, and/or treatments for repairing ocular wounds using unique and custom-designed biodendrimerbased hydrogel sealants. ? ?
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