Biologically Inspired Microstructured and Nanostructured Polymeric Biomaterials

The precise designs of nature have inspired scientists for centuries to find solutions for complex problems. By studying natural biological systems, scientist are able to identify patterns, sequences and draw conclusions in order to propose possible solutions. The interplay between chemistry and structure is a common theme in all biological systems. This interplay is often responsible for the function of a given system, for any alterations to this balance leads to undesirable result, namely, systemic malfunction. While chemists have taken advantage of biological systems, nature does not provide answers to every problem or error. Hence, the field of biomaterials combines the beauty of natural design and function with the versatility of chemistry, in the context of this thesis, polymer chemistry. Using elements from nature, polymer chemists are able to modify, functionalize and enhance the function of synthetic systems and offer solutions to complex problems in the biomedical and diagnostic fields. The focus of this thesis centers on the microfabrication of biologically inspired polymeric biomaterials. While the scope of the thesis is broad in the nature of applications considered, given the versatility of the systems developed, the main context or target application remains in the biomedical and diagnostic applications and the intersection of these two domains. The main theme and focus of this thesis is to tailor the chemistry of the system and control the microarchitecture to address relevant biomedical problems. The systems reported here target complex, yet common problems in the field such as: protein fouling on medical devices and diagnostic assays, tissue engineering scaffolding, drug delivery and wet tissue adhesives. Gaining insight into the problems from readily availed biological systems, solutions are proposed using modified polymers for promising biomaterials-based approaches. With special emphasis on tailoring the microarchitecture to specific functions, synthesis, characterization and subsequent microfabrication and testing are reported. Keeping the common theme of controlling the basic polymer chemistry of the system combined with careful microstructure design to address the final application, the thesis is divided into 6 chapters that are grouped to highlight various aspects of the intended applications. Chapters 2-4, address the issue of protein fouling onto medical devices and diagnostic assays. Chapter 5 addresses the microfabrication of tissue engineering scaffolds and drug delivery vehicles. Finally, chapter 6 deals with developing pressure-sensitive wet tissue adhesives. In chapter 2, titled: Reducing Protein Adsorption with Polymer-grafted Hyaluronic Acid Coatings, a novel antifouling coating system based on a thermoresponsive hyaluronic acid polymer hybrid is reported. These materials are designed, synthesized and characterized to possess reversible coating and adhesive properties at relevant physiological temperatures, presenting a nonfouling, hydrophilic layer to the solution. A comparison of the antifouling profile of hyaluronic acid to that of similar polysaccharides, namely dextran, alginate and carboxymethyl cellulose, is performed in chapter 3 under the title: Polymer-grafted Polysaccharide Coatings for Reduced Blood Protein Adsorption. A very promising application of such coatings is then designed to enhance detection accuracy and precision of clinically relevant diagnostic methods, namely enzyme-linked immunosorbent assay (ELISA), which is introduced in chapter 4, titled: Non-Fouling Hyaluronic Acid Coatings for Improved Sandwich ELISA Measurements in Plasma Mixtures. Chapter 5, entitled Microfabricated and Nanofabricated Hyaluronic Acid Constructs: Design and Applications, deals with microfabrication of tissue engineering scaffolds using a novel modified rapid prototyping method for 3D printing of modified hydrogels. Moreover, the potential of micro needles arrays (MNAs) in treating relevant disorders is also investigated. The final chapter of this thesis, Chapter 6: Microfabricated Gecko-inspired Microfibers for Enhanced Wet Tissue Adhesion, explores the wet adhesive properties of mussel-inspired wet adhesives coatings of gecko-inspired polyurethane microfibers.