Date of Award

12-2009

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Legacy Department

Bioengineering

Advisor

Webb, Ken

Committee Member

Metters , Andrew

Committee Member

Burg , Karen

Committee Member

Vyavahare , Naren

Committee Member

Mount , Andrew

Abstract

Biomaterials widely used in biomedical applications still face biocompatibility issues arising from non-specific protein adsorption on the foreign surface, and the consequent undesired cell response. Emerging evidence suggests that imparting specific bioactivity to the biomaterial's surface to elicit favorable response from cells, (like osseointegration of joint implants and endothelialization of stents) can yield much better biocompatibility results when combined with passive prevention of protein adsorption. In more complex diseases like spinal cord injury and cardiomyopathy, specific biomolecules are required to elicit desired cell responses for successful regeneration. However, for success of such biomolecule based strategies, the effects of various parameters (type of molecule, concentration, spatial and temporal distribution) on the behavior of target cells need to be thoroughly investigated.
Surface-initiated photoiniferter-mediated polymerization (SIPMP) was selected for this study, because it:
1. can graft protein-resistant polymer (like poly(ethylene glycol) (PEG), poly(hydroxyethyl methacrylate) (HEMA)) on any biomaterial surface.
2. provides excellent control over the amount of polymer grafted.
3. allows covalent immobilization of biomolecules on the polymer chains, and
4. allows creation of spatial patterns and concentration gradients of biomolecules by spatially controlling polymer grafting.
As the first step, poly(methacrylic acid) (pMAA) grafting via SIPMP was used to systematically control the hydrophilicity and the concentration of attached molecules on polyurethane surfaces by varying the iniferter concentration, monomer concentration, UV intensity and UV exposure time. In the next step, covalent conjugation of a hormone noradrenalin (NA) to pMAA and pHEMA chains grafted on glass surfaces was achieved as a means to develop a novel anti-marine biofouling surface. Accessibility and bioactivity of conjugated NA was confirmed by its deleterious effects on viability and cell structure of oyster hemocytes. Finally, thickness gradients of pMAA and pHEMA chains were created on glass surface as a means to create protein concentration gradients and study their effects on gradient-dependent cell behaviors. Preliminary experiments for controlling cell adhesion by conjugating proteins to homogeneous pHEMA layers remain inconclusive, warranting further investigation. In summary, the results obtained in this study highlight the versatility of SIPMP for high throughput analysis of cell behavior on surfaces with a wide variety of bioactive functionalities.

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