| dc.description.abstract | Hydrogels, crosslinked hydrophilic polymer networks, are widely used as biomaterials because of their similarity to soft biological tissues; however, their poor mechanical properties greatly limit their utility. This work focuses on enhancing the mechanical robustness of hydrogels without diminishing their numerous favorable characteristics such as hydration, biocompatibility, diffusivity and lubricity. Double network (DN) hydrogels, consisting of two independent and asymmetrically crosslinked polymer networks, have been previously shown to achieve notable mechanical properties such as ultra-high strength. Herein, by utilizing a DN hydrogel design and tailoring the composition of each network, mechanically robust hydrogel biomaterials have been developed towards two distinct applications: subcutaneous glucose biosensor membranes and synthetic cartilage. Current transcutaneous continuous glucose monitors (CGMs) have limited lifetimes due to biofouling on the implant surface which leads to an increase in local metabolism of glucose and a reduction in glucose diffusion. To minimize this foreign body reaction, a thermoresponsive, DN hydrogel membrane was designed to enhance biocompatibility through the removal of adhered cells via cyclical deswelling/reswelling, induced by natural body temperature fluctuations. The first generation of the “selfcleaning” membrane consisted of two thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm) networks with embedded polysiloxane nanoparticles for increased thermosensitivity. Although this membrane demonstrated excellent biocompatibility, improved mechanical properties would enhance long-term durability. Therefore, the second generation self-cleaning membrane incorporated an anionic copolymer into the 1st network, enhancing both the swelling kinetics and the mechanical properties. These anionic DNs exhibited remarkable strength (~25x stronger than conventional hydrogels) as well as biocompatibility up to 90 days. There is tremendous need for synthetic, off-the-shelf replacements for articular cartilage to avoid limitations of current chondral defect treatments such as donor site morbidity in autografting and mechanical mismatch in focal resurfacing. Towards a loadbearing application, the strength and stiffness of these PNIPAAm-based DNs were increased significantly without diminishing their hydration and lubricity. By tuning the polymer compositions and concentrations, hydrophobic and/or electrostatic secondary interactions were introduced between the polymer chains as sacrificial, reversible bonds. Ultimately, two ultra-strong DNs, thermoresponsive (PAMPS/P(NIPAAm-coMEDSAH)) and non-thermoresponsive at body temperature (PAMPS/P(NIPAAm-coAAm)), were developed with cartilage-mimetic properties, including strength, stiffness, hydration and lubricity, never before achieved in literature. | |
