We propose a systematic study to test the hypothesis that light-activated polymers can replace or supplement conventional sutures in ophthalmic surgeries. Specifically we have synthesized novel dendrimers, termed biodendrimers, composed of biocompatible monomers such as glycerol and lactic acid. We will take advantage of the favorable chemical and physical properties of these photocrosslinkable biodendrimers to seal corneal perforations and to secure corneal autografts in human enucleated eyes and chicken eyes in vivo. Accordingly, answers will be sought to the following questions: 1. Can the chemical structure of a biodendrimer be optimized to afford specific properties required for sutureless ophthalmic surgeries? 2. Will a biodendrimer seal a 3 mm full thickness linear or stellate corneal perforation? 3. Will a biodendrimer secure a corneal autograft? Corneal perforation and corneal transplantation are two models of corneal tissue injury that are ideal for testing new tissue sealants. The traditional approach to repair both these injuries involves sutures, yet the use of sutures affords a number of limitations and complications. Tissue adhesives such as cyanoacrylate are becoming more widely accepted in various corneal procedures, however these materials have only met with marginal success. Improvements made to the composition and/or to the method of application can potentially enhance the effectiveness of tissue sealants for treating wounds and even broaden the scope of clinical use. Potential indications in other ophthalmic areas include ruptured globe repair, wound closure in cataract surgery, and wound modulation in glaucoma filtering surgery. The novel photocrosslinkable biodendrimers described in this proposal represent a new class of ophthalmic tissue adhesives that may accomplish the objectives cited above sealing corneal perforations, and securing corneal autografts. Successful completion of these studies may lead to new ophthalmic surgical techniques, procedures, and treatments using unique, custom-designed biomaterials.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY013881-05
Application #
6870165
Study Section
Surgery and Bioengineering Study Section (SB)
Program Officer
Fisher, Richard S
Project Start
2002-02-01
Project End
2006-09-29
Budget Start
2005-02-01
Budget End
2006-09-29
Support Year
5
Fiscal Year
2005
Total Cost
$313,650
Indirect Cost
Name
Boston University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
049435266
City
Boston
State
MA
Country
United States
Zip Code
02215
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Ghobril, C; Grinstaff, M W (2015) The chemistry and engineering of polymeric hydrogel adhesives for wound closure: a tutorial. Chem Soc Rev 44:1820-35
Wen, Yifen; Oh, Jung Kwon (2014) Recent strategies to develop polysaccharide-based nanomaterials for biomedical applications. Macromol Rapid Commun 35:1819-32
Zhang, Heng; Grinstaff, Mark W (2014) Recent advances in glycerol polymers: chemistry and biomedical applications. Macromol Rapid Commun 35:1906-24
Oelker, Abigail M; Berlin, Jason A; Wathier, Michel et al. (2011) Synthesis and characterization of dendron cross-linked PEG hydrogels as corneal adhesives. Biomacromolecules 12:1658-65
Johnson, C Starck; Wathier, Michel; Grinstaff, Mark et al. (2009) In vitro sealing of clear corneal cataract incisions with a novel biodendrimer adhesive. Arch Ophthalmol 127:430-4
Berdahl, John P; Johnson, C Stark; Proia, Alan D et al. (2009) Comparison of sutures and dendritic polymer adhesives for corneal laceration repair in an in vivo chicken model. Arch Ophthalmol 127:442-7
Degoricija, Lovorka; Bansal, Prashant N; Sontjens, Serge H M et al. (2008) Hydrogels for osteochondral repair based on photocrosslinkable carbamate dendrimers. Biomacromolecules 9:2863-72
Degoricija, Lovorka; Johnson, C Starck; Wathier, Michel et al. (2007) Photo cross-linkable Biodendrimers as ophthalmic adhesives for central lacerations and penetrating keratoplasties. Invest Ophthalmol Vis Sci 48:2037-42
Kang, Paul C; Carnahan, Michael A; Wathier, Michel et al. (2005) Novel tissue adhesives to secure laser in situ keratomileusis flaps. J Cataract Refract Surg 31:1208-12

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