Poly(glycerol carbonate) pressure sensitive adhesives for the in vivo closure of alveolar pleural fistulae

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Project Summary/Abstract This fellowship will support the interdisciplinary research and training of Ms. Danielle Fitzgerald under the co-sponsorship of Dr. Mark Grinstaff of Boston University and Dr. Yolonda Colson of the Massachusetts General Hospital/Harvard Medical School’s. The training aspects of the proposal include four pillars: interdisciplinary research, multi-disciplinary mentoring, academic engineer-scientist training, and professional development. This personalized training plan provides a unique opportunity for learning in the biomaterials area with critical clinical input, and specifically addresses her career goal of becoming a professor at a top-tier university. Drs. Grinstaff and Colson will continue to meet regularly with the fellow as part of her three-year plan and will provide the necessary resources (space, equipment, supplies, training, etc.) for her success. On the research front, her proposal describes new biodegradable, biocompatible pressure sensitive adhesives (PSAs), with tunable adhesion strength, for in vivo use. This innovative technology overcomes the limitation of current PSAs, which are only used topically. Together with Drs. Colson and Grinstaff, the repair of alveolar pleural fistulae was identified as a significant and problematic clinical procedure in thoracic surgery associated with increases in health care costs and high mortality rates. Today, closure of such leaks is challenging due to limited space and to an inherent pressure gradient across the fistula. Specifically, Ms. Fitzgerald is evaluating novel 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. 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 hypotheses 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 injuries. Her specific aims 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, Aim 3. Evaluate the performance of the PGC-adhesive collagen and PLA patch in porcine models. 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 from Ms. Fitzgerald’s Sponsors, co-advisors/co-mentors, and dissertation committee members included.