PROJECT SUMMARY/ABSTRACT * This proposal describes new biodegradable, biocompatible pressure sensitive adhesives (PSAs) with tunable adhesion strength for in vivo use. Thus, this innovative technology overcomes the limitation of current PSAs which are only used topically and broadens the scope of applications of such biomaterials in patient care. To highlight the utility of these new PSAs, we identified two significant and problematic clinical procedures in thoracic surgery associated with increases in health care costs and high mortality rates: the repair of alveolar- and broncho- pleural fistulae. Today, closure of such leaks is challenging due to use in a contained space and to an inherent pressure gradient across the fistula. Survival is directly related to successful fistula closure and prevention of pleural infection through the fistula. Specifically, we are evaluating novel poly(1,2-glyceric acid carbonate)s and poly(1,2-glycerol carbonate)s (PGCs) which functionally mimic conventional polyacrylate PSAs but possess biodegradable carbonate linkages and degrade into benign products – e.g., glycerol, CO2, ethanol. These first-of-their-kind polymers provide an opportunity to create a new class of PSAs and shift the paradigm around our ability to control and manage intrathoracic wounds. The proposed experiments will test the hy- potheses that these PGC based pressure sensitive adhesives will: 1) exhibit compositionally dependent adhesive strength which positively correlates with greater molecular weight, longer alkyl chains, and stereoregularity; 2) display peel strengths which can be tuned over a wide range from Post-it® note to Duct® Tape like performance; and, 3) enable securing a collagen buttress to a surgical stapler or an electrospun polylactide mesh patch for sealing lung and bronchial injuries. Importantly, preliminary data support these hypotheses, and well-characterized materials and rigorous experimental designs are established in this proposal with essential cross-disciplinary collaborations and expertise. The specific aims of this five-year proposal are: Aim 1. Synthesize and characterize a series of PGC-based pressure sensitive adhesives; Aim 2. Evaluate the compatibility of the PGC-adhesive collagen and PLA patch in vitro and in vivo, and inhibition of bacteria migration in vitro; and, Aim 3. Evaluate the performance of the PGC-adhesive collagen and PLA patch in an in vivo porcine model.