A REVERSIBLE THERMOSENSITIVE ADHESIVE FOR RETINAL IMPLANTS In Vivo Experience with Plasma-deposited Poly(N-Isopropyl Acrylamide) MURAT TUNC, MD,*† MARK HUMAYUN, MD,* XUANHONG CHENG, PHD,‡ BUDDY D. RATNER, PHD§ Purpose: To study the in vivo effects of a thermosensitive retinal adhesive, plasma- polymerized N-isopropyl acrylamide (ppNIPAM), in rabbit eyes. Methods: Parylene C(poly(monochloro-p-xylylene)) (20 m) and poly(dimethyl siloxane) (PDMS) (200 m) coated with ppNIPAM were used as implant materials. Following pars plana vitrectomy (PPV), ppNIPAM coated parylene (n = 3) and PDMS (n = 3) implants were inserted over the retina in six rabbits. Baseline and follow-up imaging (color fundus photographs, fluorescein angiography, and optic coherence tomography [OCT]) and elec- troretinogram recordings were performed. Histologic evaluation was performed following enucleation at 6 weeks. Results: Intraoperative retinal adhesion occurred in all eyes with ppNIPAM coated parylene and PDMS implants. Two eyes developed retinal tears during the implantation procedure and the ppNIPAM coated implants closed the retinal tears successfully preventing retinal detach- ment. OCT findings confirmed the retinal adhesion in all eyes. Four weeks after implantation one parylene and one PDMS implant detached partly from the retinal surface. Histology showed mild changes at the outer retinal segments. There was no evidence of ocular toxicity and inflammation. None of the eyes that had an implant covering the retinal tear developed a retinal detachment but had some inflammatory changes around the implants. Conclusions: ppNIPAM coated implants may provide retinal adhesion in vivo without measurable ocular toxicity in the short term. Covering a retinal tear, the ppNIPAM coated implants may prevent retinal detachment. RETINA 28:1338 –1343, 2008 T here has been a growing interest in the use of tissue adhesives in ophthalmology since Bloom- field et al 1 first used methyl-2-cyanoacrylate for con- junctival flaps in 1963. Since then, numerous reports have been published on various tissue adhesives; how- ever, inadequate tensile strength, difficulties in appli- cation, toxicity, and inflammation limited their use in ophthalmic practice. 2–9 The ideal adhesive for intraocular use should be noninflammatory and nontoxic, have sufficient dura- tion and strength of adhesion, and be easily deliver- able. Reversibility is also a desired feature especially when temporary intraocular implantation of a sus- tained drug delivery or biomimetic microelectronic device is required. Recently we reported the efficiency of a thermosen- sitive polymer, plasma poylmerized-N-iso-propyl acrylamide (ppNIPAM), to implant materials over the retinal surface in vitro. 10 This polymer shows a From *Doheny Eye Institute, University of Southern California, Los Angeles; †Duzce University Medical School, Turkey; ‡the Department of Materials Sciences and Engineering and Program of Bioengineering, Lehigh University, Bethlehem, Pennsylvania; and §Bioengineering Department and Department of Chemistry, Uni- versity of Washington Engineered Biomaterials, University of Washington, Seattle. Supported by the National Science Foundation to UWEB ERC (EEC 9529161). Reprint requests: Murat Tunc, MD, Inkilap Sok 19-1, Kizilay– Ankara 06420, Turkey; e-mail: mtunc@isbank.net.tr 1338