Click Functionalized Polymeric Biomaterials for Tissue Engineering

Abstract

ECM-mimicking biomaterial research has driven numerous advances in tissue engineering in recent years, as new developments in polymer chemistry and cell-material interactions have allowed bioengineers to create complex rationally designed yet physiologically relevant biomaterials. These new 3D biomaterial platforms can provide new insights for bioengineering as we study cell fate, drug delivery, or the ability for material platforms to guide regenerative medicine. Despite these recent advances, there is still a need for a ubiquitous material crosslinking system that is capable of addressing multiple scientific questions, rather than specific materials tailored to specific problems in tissue engineering. Thus, the guiding hypothesis of this thesis is that we can functionalize naturally occurring biopolymers to crosslink via a biocompatible click chemical reaction to create a tunable biomaterial platform for tissue engineering or 3D bioprinting applications. This thesis will explore the ability to crosslink different alginate or gelatin polymer systems with a bioorthogonal, cytocompatible, and facile click chemical reaction between tetrazine and norbornene. Polymer chemical characterization, hydrogel mechanical characterization, and biological cell characterization studies are shown to demonstrate the utility of these novel biomaterial systems. A 3D bioprinting application of the click gelatin materials is also presented to highlight the amenability of this crosslinking chemistry to create novel tissue constructs. Together, the results presented in this thesis showcase a novel polymer platform that improves the functionality of commonly used biopolymers to allow bioengineers to answer complex research questions in the field of tissue engineering.