Structured Cellulose Nanocrystal Composite Hydrogels for Biomedical Applications

Abstract

Tissue engineering aims to regenerate living tissues using biomaterial scaffolds; a successful scaffold should effectively mimic the native microenvironment of a particular tissue, promoting the proliferation, differentiation, and natural integration of new functional cells. Hydrogels are a particularly interesting class of biomaterial scaffolds due to their high water content, controllable porosity, tissue compatibility in a range of biological environments, and relative chemical tailorability. However, traditional bulk hydrogels exhibit several shortcomings that limit the potential clinical translation of such materials. This thesis aims to solve some of these critical shortcomings, namely (1) enabling minimally invasive delivery, (2) enhancing mechanical performance, and (3) facilitating tailorable network structuring/anisotropy. Herein, we demonstrate a platform of composite hydrogels based on synthetic poly(oligoethylene glycol methacrylate) (POEGMA) and rigid, anisotropic cellulose nanocrystals (CNCs), prepared via several different techniques. First, by functionalizing POEGMA with aldehyde and hydrazide moieties, the resulting hydrogels are rendered injectable via kinetically bio-orthogonal hydrazone bond formation upon extrusion through a double barrel syringe. By physically incorporating CNCs into the POEGMA mixture, the resulting injectable hydrogels display drastically enhanced mechanical properties. Furthermore, by employing preparation techniques such as thermal shrinking and freeze casting, the POEGMA-CNC hydrogel network structure can be controlled from 2D to 3D. Finally, we demonstrate in situ magnetic alignment of CNCs within POEGMA hydrogels to prepare scaffolds that are simultaneously injectable, mechanically strong, and anisotropic. The effects of CNC and POEGMA concentrations, POEGMA composition, CNC orientation, and crosslink density are studied to determine their effects on hydrogel properties such as mechanical strength, swelling, gelation time, network structuring, cell adhesion, and inflammatory tissue responses. We believe that the formation of mechanically and structurally tunable POEGMA-CNC composite hydrogels offers immense opportunity as an intelligent, high strength biomaterial capable of engineering various tissue types.