ABSTRACT: While multiple types of smart, environmentally-responsive materials have been explored for a variety of biomedical applications (e.g. drug delivery, tissue engineering, bioimaging, etc.), their ultimate clinical use has been hampered by their lack of biologically-relevant degradation as well as challenges regarding their non-surgical administration to the body. These factors have particularly limited the clinical use of temperature-responsive hydrogels, which are either highly labile in diluting environments like the body (e.g. Pluronics formulations) and/or based on functionally non-degradable synthetic polymers with carbon-carbon backbones (e.g. poly(N-isopropylacrylamide) (PNIPAM) or poly(oligoethylene glycol methacrylate) (POEGMA)). As such, to effectively translate the potential of thermoresponsive hydrogels to the challenges of remote-controlled or metabolism-regulated drug delivery, cell scaffolds with tunable cell-material interactions, theranostic materials with the potential for both imaging and drug delivery, and other such applications, it is necessary to develop hydrogel chemistries that can form gels following administration via minimally-invasive injection procedures and facilitate gel degradation over targeted time intervals such that the degradation products are capable of renal clearance following the required lifetime of the material. In this presentation, I will outline the recent progress made in my group toward engineering injectable and degradable smart hydrogels on multiple length scales based on in situ gelation of hydrazide and aldehyde-functionalized PNIPAM or POEGMA oligomers with molecular weights below the renal filtration limit. Specifically, approaches we have developed to fabricate degradable thermoresponsive bulk hydrogels (using a double barrel syringe technique), hydrogel particles (on both the microscale through the use of a microfluidics platform facilitating simultaneous mixing and emulsification of the precursor polymers and the nanoscale through the use of a new thermally-driven self-assembly and cross-linking method), hydrogel nanofibers (using a reactive electrospinning strategy), and degradable gel coatings (via reactive dip-coating and ink jet printing) will be described. In each case, hydrogels with temperature-responsive properties similar to those achieved via conventional free radical cross-linking processes can be achieved, but the hydrazone cross-linked network can both enable rapid gelation upon injection and controllable degradation over time to re-form the oligomeric precursor polymers and enable clearance. Applications of these materials for drug delivery, cell delivery, tissue engineering, and biosensing will be discussed in conjunction with the various hydrogel morphologies we can generate. Overall, we anticipate that the tools developed will enable easier translation of synthetic smart materials to clinical applications.
Bio-Sketch: Todd Hoare is an Associate Professor and University Scholar in the Department of Chemical Engineering at McMaster University and the Canada Research Chair in Engineered Smart Materials (Tier 2). He received a B.Sc. (Eng.) in Engineering Chemistry from Queen’s University in 2001 and a Ph.D. in Chemical Engineering from McMaster in 2006. He returned to McMaster in 2008 to join the faculty after a two-year NSERC (Natural Sciences and Engineering Research Council of Canada)-sponsored post-doctoral fellowship in Robert Langer’s laboratory at the Massachusetts Institute of Technology. Dr. Hoare’s work in engineering hydrogels and smart nanoparticles for biomedical applications has been profiled by Popular Science, Maclean’s, and BBC for its potential in solving clinical challenges through innovative smart materials design. He has won an NSERC Innovation Challenge award recognizing the novelty of his research. He also received the 2016 Early Career Investigator Award from the Canadian Biomaterials Society, a 2010 Early Researcher Award, and the 2009 John Charles Polanyi Prize in Chemistry from the Government of Ontario recognizing his accomplishments in his early career as a researcher and was a finalist for the 2012 President's Award for Graduate Supervision. Dr. Hoare is currently the Associate Editor of Chemical Engineering Journal and is a member of the Editorial Advisory Boards of Biomacromolecules and Colloid and Polymer Science. He is also the current President of the Canadian Biomaterials Society and Past-President of the Canadian Chapter of the Controlled Release Society.