| Polymeric materials are used in numerous biomedical applications. Ultrafiltration blood dialysis membranes, polymeric tissue engineering scaffolds, drug-releasing composites, mesh wound dressings, and materials with anti-biofouling surfaces all rely on the desirable bulk properties of the polymer material (e.g., porosity, flexibility, mechanical strength). These materials, however, are prone to fouling by bacteria, proteins, and other macromolecules present in medical settings, ultimately decreasing material performance and lifetime. Moreover, with millions of biomedical devices deployed annually, hospital acquired infections are the cause of death for ~10% of American patients. To combat infection associated with biofouling, surface modification techniques are often employed to customize material surface properties yet retain the desired bulk characteristics. Low-temperature plasmas (LTPs) are well suited for biomedical device processing, as they provide a sterile environment with a large parameter space that allows for tunable surface modification and the ability to retain the bulk properties of the polymer. Indeed, a large body of literature successfully describes the plasma processing of a variety of polymeric constructs for enhanced biocompatibility. More recently, plasmas have been investigated for the optimization of antibacterial polymeric materials. In this dissertation, plasma processing techniques, including H2O(v) plasma surface modification and plasma enhanced chemical vapor deposition (PECVD), are used to (1) customize the surface properties of medically-relevant polymeric constructs towards improved wettability and biological outcomes and (2) enhance material antibacterial performance via tuning drug release or fabricating antifouling surfaces. Plasma processed materials are characterized with respect to changes in chemistry and wettability via X-ray photoelectron spectroscopy (XPS) and water contact angle goniometry, respectively. Biological evaluation strategies include the quantification of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) population over time as well as numerous imaging techniques to assess bacteria after attachment and biofilm formation. More advanced biological performance testing has included static and dynamic protein fouling, water and protein flux studies, and thromboelastographic analysis of modified materials. Gas-phase spectroscopic techniques (e.g., optical emission spectroscopy), in combination with surface analysis and biological performance metrics, provide comprehensive insight into how plasma characteristics can be correlated to material properties, and, thus, interactions with bacteria and protein. The dissertation begins with water vapor [H2O(v)] plasma surface modification to create hydrophilic ultrafiltration polysulfone membranes. XPS revealed the permanency (>2 months) of the treatment arose from covalent incorporation of hydrophilic, oxygen-containing functional groups into the polymer backbone. Modified membranes demonstrated enhanced hydrodynamic characteristics and no longer required preconditioning, rendering them more practical for deployment in medical separations. Importantly, scanning electron microscopy (SEM) revealed no damage to the porous morphology from plasma treatment, thus, water vapor plasma modification provides a potential route to extend ultrafiltration membrane lifetime. Chapter 4 highlights current fabrication and characterization methodologies for silver nanoparticle (AgNP)-loaded polymeric constructs, often researched for potential applications as drug delivery systems, wound dressings, and anti-biofouling materials. Several methods were used to fabricate AgNP-loaded materials and their efficacy against E. coli was evaluated. H2O(v) plasma surface modification was employed to enhance material surface wettability (explored by water contact angle goniometry) and nanoparticle incorporation. Compositional analyses reveal incorporation of AgNPs on the surface and bulk of the materials strongly depends on the fabrication methodology. More importantly, the nature of AgNP incorporation into the polymer has direct implications on the biocidal performance resulting from release of Ag+. The materials fell significantly short of healthcare standards with respect to antimicrobial behavior, and, in comparing our results to numerous literature studies. Notably, we identified a glaring disparity in the way biological results are often described. Thus, Chapter 4 also contains a critical evaluation of the literature, highlighting select poor-performing materials to demonstrate several shortcomings in the quantitative analysis and reporting of the antibacterial efficacy of AgNP-loaded materials. Ultimately, we provide recommendations for best practices for better evaluation of these constructs towards improved antibacterial efficacy in medical settings. TygonRTM and other poly(vinyl chloride)-derived polymers are frequently used for tubing in blood transfusions, hemodialysis, and other extracorporeal circuit applications. These materials, however, tend to promote bacterial proliferation which contributes to the high risk of infection associated with device use. Antibacterial agents, such as nitric oxide (NO) donors, can be incorporated into these materials to eliminate bacteria before they can proliferate. The release of the antimicrobial agent from the device, however, is challenging to control and sustain on timescales relevant to blood transport procedures. Surface modification techniques can be employed to address challenges with controlled drug release. In Chapter 5, surface modification using H2O(v) plasma is explored as a potential method to improve the biocompatibility of biomedical polymers, namely to tune the NO-releasing capabilities from TygonRTM films. Film properties are evaluated pre- and post-treatment by contact angle goniometry, XPS, and optical profilometry. H2O(v) plasma treatment significantly enhances the wettability of the nitric-oxide releasing films, doubles film oxygen content, and maintains surface roughness. Using the kill rate method, we determine both treated and untreated films cause an 8-log reduction in the population of both gram-negative E. coli and gram-positive S. aureus. Notably, however, H2O(v) plasma treatment delays the kill rate of treated films by 24 h, yet antibacterial efficacy is not diminished. NO release, measured via chemiluminescent detection, is also reported and correlated to the observed kill rate behavior. Overall, the delay in biocidal agent release caused by our treatment indicates plasma surface modification is an important route toward achieving controlled drug release from polymeric biomedical devices. Chapter 6 describes the use of PECVD to deposit a film of 1,8-cineole, an antibacterial constituent of tea tree oil, on two-dimensional (2D) substrates. The resulting conformal, pinhole free films were highly customizable with respect to oxygen content and wettability. Notably, film wettability increased linearly with plasma pressure, yielding water contact angles ranging from ~50° to ~90°. XPS revealed less oxygen is incorporated at higher pressures, likely arising from the lower density of OH(g) species, as observed via optical emission spectroscopy. Further, we utilized H2O(v) plasma surface modification of the films to improve wettability and found this results in a substantial increase in surface oxygen content. To elucidate the role of film wettability and antibacterial properties, both as-deposited and H2O(v) plasma modified films were exposed to gram-negative E. coli and gram-positive S. aureus. In short, these essential oil-based films significantly reduced biofilm formation (4-7% coverage compared to ~40% for controls). Chapter 7 expands on the essential oil work described in Chapter 6 by extending PECVD systems to two additional precursors as well as introducing three-dimensional (3D) porous polymeric substrates. Films from 1,8-cineole and terpinen-4-ol were deposited onto ultrafiltration membranes and porous scaffolds. Coated constructs were exposed to E. coli and bacterial attachment on the constructs was evaluated by colony counting and SEM techniques. Importantly, we demonstrate films from terpinen-4-ol can be deposited via plasma polymerization techniques. Using results from gas phase analyses and surface characterization, we make comparisons between films discussed in Chapter 6 and films deposited from similar essential-oil derived molecules. This dissertation concludes with work expanding on that described in Chapter 3, exploring the H2O(v) plasma surface modification of ultrafiltration membranes. Specifically, we discuss setbacks often faced when working with industrial membranes and how these pose challenges to plasma processing and surface analysis. Chapter 8 concludes by providing insight into how changes in membrane composition may counteract desirable properties gained by plasma processing. |
