Conformal encapsulation of three-dimensional, bioresorbable polymeric scaffolds using plasma-enhanced chemical vapor deposition.

Bioresorbable polymers such as poly(ε-caprolactone) (PCL) have a multitude of potential biomaterial applications such as controlled-release drug delivery and regenerative tissue engineering. For such biological applications, the fabrication of porous three-dimensional bioresorbable materials with tunable surface chemistry is critical to maximize their surface-to-volume ratio, mimic the extracellular matrix, and increase drug-loading capacity. Here, two different fluorocarbon (FC) precursors (octofluoropropane (C3F8) and hexafluoropropylene oxide (HFPO)) were used to deposit FC films on PCL scaffolds using plasma-enhanced chemical vapor deposition (PECVD). These two coating systems were chosen with the intent of modifying the scaffold surfaces to be bio-nonreactive while maintaining desirable bulk properties of the scaffold. X-ray photoelectron spectroscopy showed high-CF2 content films were deposited on both the exterior and interior of PCL scaffolds and that deposition behavior is PECVD system specific. Scanning electron microscopy data confirmed that FC film deposition yielded conformal rather than blanket coatings as the porous scaffold structure was maintained after plasma treatment. Treated scaffolds seeded with human dermal fibroblasts (HDF) demonstrate that the cells do not attach after 72 h and that the scaffolds are noncytotoxic to HDF. This work demonstrates conformal FC coatings can be deposited on 3D polymeric scaffolds using PECVD to fabricate 3D bio-nonreactive materials.

Gas phase energetics of CN radicals in radio frequency discharges: influence on surface reaction probability during deposition of carbon nitride films.

The CN radical has been implicated as an important contributor to the plasma deposition of amorphous carbon nitride. Here, laser-induced fluorescence and optical emission spectroscopy were used to explore in greater detail the gas phase energetics of CN in CH(3)CN, BrCN, and CH(4)/N(2) plasmas. Measurements of CN internal temperatures from these systems yield rotational temperatures well above 300 K, with notably higher ones for CN formed in BrCN plasmas, and vibrational temperatures of 4500-6000 K in all three systems. The data agree with the results of literature photodissociation experiments, and extension of those results to the plasma systems studied here provides insight into both the mechanisms for CN formation as well as the disposal of energy during fragmentation of the parent molecules. The internal energies of these species may influence their surface behavior; this issue is discussed in the context of previous work from our lab as well as others. The apparent trends not only offer a valuable perspective on the chemical dynamics of CN during the plasma deposition of a-CN(x) films but are also suggestive of a more general relationship between the energetics of plasma species and their behavior at surfaces.

Perspectives on antibacterial performance of silver nanoparticle-loaded three-dimensional polymeric constructs.

Silver nanoparticle (AgNP)-loaded polymeric constructs are widely investigated for potential applications as drug delivery systems, wound dressings, and antibiofouling biomaterials. Herein, the authors present several methods for fabricating such materials and evaluate their efficacy against Escherichia coli. H2O(v) plasma surface modification is employed to enhance material surface wettability (explored by water contact angle goniometry) and nanoparticle incorporation. Compositional analyses reveal that 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 the release of Ag+. The materials fabricated herein fell significantly short of healthcare standards with respect to antimicrobial behavior, and, in comparing their results to numerous literature studies, the authors identified a glaring disparity in the way such results are often described. Thus, this work 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, recommendations for best practices for better evaluation of these constructs toward improved antibacterial efficacy in medical settings are provided.

Time of flight secondary ion mass spectrometry-A method to evaluate plasma-modified three-dimensional scaffold chemistry.

Biopolymers are used extensively in the manufacture of porous scaffolds for a variety of biological applications. The surfaces of these scaffolds are often modified to encourage specific interactions such as surface modification of scaffolds to prevent fouling or to promote a cell supportive environment for tissue engineering implants. However, few techniques can effectively characterize the uniformity of surface modifications in a porous scaffold. By filling the scaffold pores through polymer embedding, followed by analysis with imaging time-of-flight secondary ion mass spectrometry (ToF-SIMS), the distribution and composition of surface chemical species though complex porous scaffolds can be characterized. This method is demonstrated on poly(caprolactone) scaffolds modified with a low-fouling plasma-deposited coating from octafluoropropane via plasma enhanced chemical vapor deposition. A gradient distribution of CF+/CF3+ is observed for scaffolds plasma treated for 5 min, whereas a 20 min treatment results in more uniform distribution of the surface modification throughout the entire scaffold. The authors expect this approach to be widely applicable for ToF-SIMS analysis of scaffolds modified by multiple plasma processing techniques as well as alternative surface modification approaches.

Modification of a commercial thromboelastography instrument to measure coagulation dynamics with three-dimensional biomaterials.

Three-dimensional synthetic constructs with complex geometries have immense potential for use in a multitude of blood-contacting applications. Understanding coagulation phenomena is arguably the most critical aspect for applications involving synthetic biomaterials; however, real-time evaluation of the clot formation while interfacing with these materials is difficult to achieve in a reproducible and robust manner. Here, work representing first steps toward addressing this deficit is presented, wherein modified consumables for a clinical instrument (a Thromboelastograph(®)) have been fabricated. Thromboelastography (TEG) measures viscoelastic properties throughout clot formation and therefore provides clinically relevant coagulation measurements in real time (i.e., kinetics and strength of clot formation). Through our modification, TEG consumables can readily accommodate three-dimensional materials (e.g., those for regenerative tissue applications). The authors performed proof-of-concept experiments using polymer scaffolds with a range of surface properties and demonstrated that variations in surface properties resulted in differences in blood plasma coagulation dynamics. For example, the maximum rate of thrombus generation ranged from 22.2 ± 2.2 (dyn/cm(2))/s for fluorocarbon coated scaffolds to 8.7 ± 1.0 (dyn/cm(2))/s for nitrogen-containing scaffolds. Through this work, the ability to make real-time coagulation activity measurements during constant coagulation factor interface with biomedically relevant materials is demonstrated.

Plasma-modified nitric oxide-releasing polymer films exhibit time-delayed 8-log reduction in growth of bacteria.

Tygon(®) 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 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. Here, surface modification using H2O (v) plasma is explored as a potential method to improve the biocompatibility of biomedical polymers, namely, to tune the nitric oxide-releasing capabilities from Tygon films. Film properties are evaluated pre- and post-treatment by contact angle goniometry, x-ray photoelectron spectroscopy, 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, the authors determine both treated and untreated films cause an 8 log reduction in the population of both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. Notably, however, H2O (v) plasma treatment delays the kill rate of treated films by 24 h, yet antibacterial efficacy is not diminished. Results of nitric oxide release, measured via chemiluminescent detection, are also reported and correlated to the observed kill rate behavior. Overall, the observed delay in biocidal agent release caused by our treatment indicates that plasma surface modification is an important route toward achieving controlled drug release from polymeric biomedical devices.

Synthesis and properties of plasma-polymerized polypyrrole/Au composite nanofibers.

Nanostructured composites have a wide variety of potential applications in microelectronics, chemical sensors, and electrochemical energy production. Here, we report the chemical, structural, and electrochemical characteristics of a nanostructured composite material formed from plasma-polymerized polypyrrole-coated Au fibers. The properties of the plasma-polymerized polypyrrole (PPPy) films were characterized by FTIR, X-ray photoelectron spectroscopy (XPS), and UV-Vis spectroscopy, as well as cyclic voltammetry (CV), and scanning electron microscopy (SEM). These spectroscopy analyses suggest that thermal treatment of the materials results in elimination of loosely-bound, low mass oligomers in the films. Mass spectral analysis of the plasma phase suggests that plasma polymerization of the pyrrole takes place on the substrate surface as a result of diffusion of radicals produced in the plasma. In addition, thermal treatment enhances the electrochemical properties of the PPPy films because of changes in the surface morphology and bulk structure of the films. However, as-deposited PPPy films coated on Au nanotubes demonstrate better electrochemical properties than as-deposited PPPy films coated on flat ITO electrodes as a result of the increase in surface area and decrease in film thickness.

Challenges in the characterization of plasma-processed three-dimensional polymeric scaffolds for biomedical applications.

Low-temperature plasmas offer a versatile method for delivering tailored functionality to a range of materials. Despite the vast array of choices offered by plasma processing techniques, there remain a significant number of hurdles that must be overcome to allow this methodology to realize its full potential in the area of biocompatible materials. Challenges include issues associated with analytical characterization, material structure, plasma processing, and uniform composition following treatment. Specific examples and solutions are presented utilizing results from analyses of three-dimensional (3D) poly(ε-caprolactone) scaffolds treated with different plasma surface modification strategies that illustrate these challenges well. Notably, many of these strategies result in 3D scaffolds that are extremely hydrophilic and that enhance human Saos-2 osteoblast cell growth and proliferation, which are promising results for applications including tissue engineering and advanced biomedical devices.