Gelatin-Based Biomimetic Tissue Adhesive. Potential for Retinal Reattachment Tianhong Chen, 1 Rabeea Janjua, 2 Martin K. McDermott, 3 Steven L. Bernstein, 2 Scott M. Steidl, 2 Gregory F. Payne 1,4 1 Center for Biosystems Research, University of Maryland Biotechnology Institute, 5115 Plant Sciences Building, College Park, Maryland 20742 2 Department of Ophthalmology, University of Maryland at Baltimore, 419 West Redwood St., Baltimore, Maryland 21201- 1734 3 Division of Mechanics and Materials Science, Office of Science and Technology, Food and Drug Administration, 9200 Corporate Blvd., HFZ-150, Rockville, Maryland 20850 4 Department of Chemical and Biochemical Engineering, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, Maryland 21250 Received 27 April 2005; revised 21 June 2005; accepted 28 June 2005 Published online 8 November 2005 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jbm.b.30439 Abstract: An adhesive that cures under moist/wet conditions could facilitate surgical pro- cedures for retinal reattachment. We are investigating an adhesive that mimics the factor XIIIa-mediated crosslinking of fibrin that occurs in the late stages of the blood coagulation cascade. Specifically, we use gelatin as the structural protein (in place of fibrin), and crosslink gelatin using a calcium-independent microbial transglutaminase (in place of the calcium- dependent transglutaminase factor XIIIa). Injection of gelatin and microbial transglutaminase (mTG) into the vitreous cavity of Sprague Dawley white rats did not elicit structural or cellular damage to the retina as evidenced from histological evaluation 2 weeks post-injection. Qualitative in vitro studies indicate that the gelatin–mTG adhesive binds to bovine retinal tissue under wet conditions. Quantitative lap-shear tests were performed with more robust bovine tissue from the choroid and sclera. The lap-shear strength of the biomimetic gelatin– mTG adhesive was independent of tissue-type and ranged from 15 to 45 kPa, which is comparable to the values reported for other soft-tissue adhesives. These studies suggest that the mTG-crosslinked gelatin may provide a simple, safe, and effective adhesive for ophthalmic applications. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 77B: 416 – 422, 2006 Keywords: adhesive; gelatin; lap-shear; retina; transglutaminase INTRODUCTION The retina is a thin sheet of tissue (200 –250 m) 1 consist- ing of nine separate tissue layers and several layers of cells. As indicated in Figure 1(a), the outer segments of the retina’s photoreceptors rest on a monolayer of retinal pigment epi- thelial (RPE) cells that separate the retina from the choroidal blood supply. The RPE is integral to meeting the needs of the photoreceptors for nutrients and oxygen, and forms the blood–retinal barrier. There are no anatomical junctions an- choring the retina to the RPE. Rather, the retina is apposed to the RPE through a combination of metabolic and mechanical mechanisms that are not yet fully understood. 2,3 As a result of disease or injury, the retinal photoreceptors can be detached from the RPE and because the RPE is vital to the physiology of the retina, reattachment is essential to preserve sight. 4 When a retinal break occurs in the absence of detachment, retinal attachment is preserved by creating a permanent reti- nal adhesion around the break. This is accomplished by exposing the RPE to a circular area of laser light, 50 –500 microns in diameter, which induces a thermal reaction result- ing in tissue photocoagulation. This exposure to laser light is repeated in a pattern outlining the retinal defect, leading to a water-tight retinal seal. For the first three days after laser treatment, weak adhesion is created from a proteinaceous coagulum 5 that is replaced by a strong inflammatory-based scar beginning at about day 5. 6 Correspondence to: G. F. Payne (e-mail: payne@umbi.umd.edu) Contract grant sponsor: The United States’ National Science Foundation; contract grant number: BES-0114790 Contract grant sponsor: Department of Agriculture; contract grant number: 2001– 35504-10667 Contract grant sponsor: Food and Drug Administration © 2005 Wiley Periodicals, Inc. 416