Synthesis and Characterizations of Stimuli-Responsive Polymeric Materials for Biomedical Applications

Stimuli-responsive polymeric materials have been now widely researched toward the biomedical applications including therapeutic delivery, bio-sensor surface modification, and tissue-engineering, etc., considering their desirable biocompatibility, tunable properties, and sensitivity toward physiological stimuli. Beyond the monoresponsive materials, polymers with responsiveness simultaneously toward multiple stimuli are paid great attention to because the control of responsive behaviors could be achieved at a more accurately and delicately level in a complex local environment. However, many challenges still exist such as maintaining integrity of the structure, shaping the morphology at micro- and macro-scale, and regulating a controllable and predictable transition behavior.

The objectives of this dissertation are to develop and optimize multi-responsive polymeric materials toward the physiological stimuli including temperature, pH, and oxidative stress, in the forms of nano-/micro-scaled particles, nano-scaled multilayers, and macro-porous scaffolds.

Specifically, micro/nano-scale polyetheramine containing hydrogel particles with pH-, thermo-, and oxidation-responsiveness were developed via thermally induced phase separation for therapeutic delivery (Chapter 2). The physical properties, including size, surface charge density, swelling behaviors are tunable via varying the preparation parameters such as monomer ratio, reaction time and temperature, monomer concentration, and monomer composition. Cytocompatibility and drug loading capability were investigated, and proved these particles to be of great potential for biomedical applications.

For construction of dual-responsive multilayers, pH sensitivity was incorporated into a thermo-responsive polymer (poly(N-vinyl-2-caprolactam)) (PVCL) via bearing a tert-butoxycarbonylmethyl group at the 3-position of VCL through the approach of nucleophilic substitution (Chapter 3). The biocompatibility exhibited in acute cytotoxicity assay and the successful layer-by-layer self-assembly with a cationic polymer suggested a possible application for bio-sensor surface modification.

Macro-porous hydrogels with pH-, thermo-, and oxidation-responsiveness were successfully fabricated via thermally-induced phase separation of prepolymers toward the application as scaffolds for neuronal regeneration (Chapter 4). The hydrogels exhibited micro-sized interconnected cavity for diffusion of nutrition and metabolites, hydrophobic domains for therapeutic delivery, great biocompatibility in direct contact assay, and cationic functional groups for survival of neuronal cells as well as neurite outgrowth, indicating a probable use for neuronal regeneration.