January 30
@
12:00 PM
–
1:00 PM
Using Bottlebrush Polymers to Tackle Challenges in Drug Delivery and Tissue Engineering
Monica Ohnsorg, PhD
Postdoctoral Fellow
Department of Chemical and Biological Engineering
BioFrontiers Institute
University of Colorado Boulder
Abstract:
Macromolecular design can be a powerful tool to improve the efficacy of clinical therapeutics and develop biomaterials to support in vitro human cell-based models. In this talk, I will discuss two vignettes describing how bottlebrush polymers, macromolecular architectures which are composed of polymer chains covalently bound at one end to a linear polymer backbone, can be used to both improve oral drug delivery and study how cells respond to strain-stiffening microenvironments. First, I will introduce how bottlebrush copolymers can be used to non-covalently sequester and solubilize small molecule therapeutics. Specifically, by modulating bottlebrush polymer hydrophilicity using post-polymerization end-group modification techniques, the small molecule anti-seizure medication, phenytoin, was effectively solubilized at higher drug loadings with the bottlebrush polymer carrier compared to current industry standard excipients. Second, I will address how nonlinear elasticity, an understudied property of natural extracellular matrix, can be recapitulated using synthetic materials that support 3D cell culture. Bottlebrush polymer-based hydrogels can be used to decouple strain-stiffening biomechanical cues from stress-relaxation and observe how engineered strain-stiffening microenvironments regulate the initiation of cellular protrusion formation. Building upon these findings, I will discuss how bottlebrush polymer-based hydrogels can be used to mimic the biomechanical properties of non-mineralized, collagen type-1 rich bone osteoid to develop models of human osteocyte dendritic network formation and function. Together, these applications demonstrate how bottlebrush polymer-based materials hold great potential to recapitulate biologically relevant biomechanical and biochemical signals for in vitro cell culture, for tissue and disease modeling, and as therapeutic delivery vehicles in the future.
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