Thin Films And Surfaces For Bioactivity And Biomedical Applications

Author : Maggie Herron
Publisher :
ISBN 13 :
Total Pages : 0 pages
Book Rating : 4.:/5 (13 download)

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Download or read book Design and Characterization of Bioactive Thin Films written by Maggie Herron and published by . This book was released on 2016 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The work presented in this thesis focuses on the development and characterization of functionalized thin films. The thesis comprises two main sections. The first section describes polymer-based coatings/films that can be easily handled and placed onto relevant biomedical surfaces to release antibacterial, antibiofilm, or anesthetic agents. The second section discusses films of monolayers of oligopeptides/ proteins that provide control of the recruitment of water from ambient air or that can be functional in the absence of bulk water. The first section demonstrates a facile method using micrometer-thick sacrificial polyvinyl alcohol (PVA) films to transfer ultra-thin polyelectrolyte multilayer films (PEMs) onto soft biomedically-relevant surfaces (e.g. wound beds and biological dressings). Surfaces of wounds that were engineered to provide nanolocalized sustained delivery of an antibacterial agent (silver) was found to kill bacteria of Staphyloccocus aureus on mice wounds at sufficiently low doses that tissue toxicity was avoided. We showed that an antibiofilm agent (Ga3+) can be incorporated into PEMs (formed from polyallyl amine hydrochloride (PAH) and polyacrylic acid (PAA)). The relase of Ga3+ from the PEMs can be slowed down by cross-linking the PEMs (forming amide bonds between PAH and PAA). Using sacrificial PVA films, the cross-linked PEMs can be transferred onto biological dressings to release Ga3+ for up to 3 weeks. The Ga3+ released from the dressings is capable of inhibiting formation of Pseudomonas aeruginosa biofilms for up to 4 days. The sacrificial PVA films can also be used to transfer (stack) multiple PEMs (Ag+- and Ga3+-loaded PEMs as representative PEMs) to wound dressings, thereby creating a stacked structure. Simultaneous release of agents was shown to lead to synergistic effects on bacteria biofilms (killing and dispersing biofilms formed by Pseudomonas aeruginosa). We also developed microfilm constructs consisting of PEMs, PVA, and poly(lactic-co-glycolic acid) (PLGA) to co-deliver controlled doses of Ag+ (from PEM) and bupivacaine (an anesthetic agent, from PVA layer) that causes no toxicity to fibroblasts in vitro or in mice wounds but still provides antibacterial activity. These results represent a significant step toward the implementation of functional coatings on biomedically-relevant surfaces. The modular nature of the construction of the stacked PEMs and microfilm construct provides an opportunity to design multi-functional coatings that are not limited to antimicrobial purposes. The second section introduces design principles for films of oligopeptides and proteins (immobilized on surfaces). These films recruit water from ambient air or demonstrate functionality even in the absence of bulk water. Water recruitment from ambient air to oligopeptides-decorated surfaces was found to be influenced by both (i) the amino-acid composition (especially cationic residues) and (ii) the surface densities of the oligopeptides (decreasing the surface densities of oligopeptides increases the number of water molecules recruited per residue). However, a change in the site of immobilization of oligopeptides (N- versus C-terminus of MSI-78) was found not to influence water recruitment. Amino acid compositions and surface densities of immobilized proteins (nitro-reductase and 6-phospho-[beta]-galactosidase) were measured to influence water recruitment in a manner similar to the oligopeptides. In contrast to the oligopeptides, however, a change in the site of immobilization of 6-phospho-[beta]-galactosidase altered the number of water molecules recruited per residue. Overall, the results provide guidance to the design of surfaces that recruit water from the ambient air to peptide/protein-decorated surfaces. Also in the second section of the thesis, we describe a method that can protect the secondary structure of immobilized proteins, and hence allow the biomolecules to function in air (using haloalkane dehalogenase, HLD, as a model protein). Specifically, poly-sorbitol methacrylate (PSMA) (a water-mimicking molecule) was co-immobilized with HLD. The HLD that was co-immobilized with PSMA was found to perform catalytic function at a 6-times higher rate than the protein without PSMA. PSMA appears to enhance the protein activity not by simply trapping more water, but by replacing protein-water interactions, thereby preserving the protein structure in air. These results represent a significant step toward developing a general strategy to recruit water from ambient air to biomolecules-decorated surfaces and to protect the structure of immobilized biomolecules in air.