Contamination of biomedical devices in a biological medium, biofouling, is a major cause of infection and is entirely avoidable. This mini-review will coherently present the broad range of antifouling strategies, germicidal, preventive and cleaning using one or more of biological, chemical and physical techniques. These techniques will be discussed from the point of view of their ability to inhibit protein adsorption, usually the first step that eventually leads to fouling. Many of these approaches draw their inspiration from nature, such as emulating the nitric oxide production in endothelium, use of peptoids that mimic protein repellant peptides, zwitterionic functionalities found in membrane structures, and catechol functionalities used by mussel to immobilize poly(ethylene glycol) (PEG). More intriguing are the physical modifications, creation of micropatterns on the surface to control the hydration layer, making them either superhydrophobic or superhydrophilic. This has led to technologies that emulate the texture of shark skin, and the superhyprophobicity of self-cleaning textures found in lotus leaves. The mechanism of antifouling in each of these methods is described, and implementation of these ideas is illustrated with examples in a way that could be adapted to prevent infection in medical devices.

Amine functionalized poly(ethylene glycols) (PEGs) with molecular weights 2000 and 4000 Da were covalently grafted onto carboxy modified hydrophilic Sephadex derivatives and hydrophobic polystyrene derivatives using anhydrous amine conjugation methods. Varying PEG surface concentration and layer thickness were achieved by controlling the reaction parameters and were analyzed by X-ray photoelectron spectroscopy (XPS). C-O intensities obtained from high resolution C 1s scans were correlated using the standard overlay model to study the grafting kinetics as well as conformational properties of grafted polymer chains. A detailed and systematic comparison of PEG layer thickness and distance between grafted chains with the Flory radius of surface grafted PEG resulted in valuable information regarding conformational behavior of the polymer. The influence of the nature of the solid matrix on grafting kinetics and conformational properties of the grafted polymer chain was also established from the XPS results.

We report a fabrication process for coating neural probes with an ultrafast degrading polymer to create consistent and reproducible devices for neural tissue insertion. The rigid polymer coating acts as a probe insertion aid, but resorbs within hours post-implantation. Despite the feasibility for short term neural recordings from currently available neural prosthetic devices, most of these devices suffer from long term gliosis, which isolates the probes from adjacent neurons, increasing the recording impedance and stimulation threshold. The size and stiffness of implanted probes have been identified as critical factors that lead to this long term gliosis. Smaller, more flexible probes that match the mechanical properties of brain tissue could allow better long term integration by limiting the mechanical disruption of the surrounding tissue during and after probe insertion, while being flexible enough to deform with the tissue during brain movement. However, these small flexible probes inherently lack the mechanical strength to penetrate the brain on their own. In this work, we have developed a micromolding method for coating a non-functional miniaturized SU-8 probe with an ultrafast degrading tyrosine-derived polycarbonate (E5005(2K)). Coated, non-functionalized probes of varying dimensions were reproducibly fabricated with high yields. The polymer erosion/degradation profiles of the probes were characterized in vitro. The probes were also mechanically characterized in ex vivo brain tissue models by measuring buckling and insertion forces during probe insertion. The results demonstrate the ability to produce polymer coated probes of consistent quality for future in vivo use, for example to study the effects of different design parameters that may affect tissue response during long term chronic intra-cortical microelectrode neural recordings.

A new class of nitric oxide (NO)-releasing biodegradable polymers has been synthesized by derivatizing poly(lactic-co-glycolic-co-hydroxymethyl propionic acid) (PLGH) polymers with structurally unique thiol functionalities followed by nitrosation with t-butyl nitrite to yield pendant S-nitrosothiol moieties. The extent of thiolation was found to be dependent on the thiol moiety itself with the efficiency of incorporation as follows: cysteamine > cysteine > homocysteine. Glutathione and penicillamine were not incorporated to any significant extent. The structure and polymer environment associated with the pendant thiol has been related to the physicochemical properties of the resulting polymers. To quantify the extent of S-nitrosation, chemiluminescence and UV-visible spectroscopy techniques were employed in combination. The cysteamine and homocysteine derivatives were found to have the highest extent of nitrosation at 93 AE 3% and 96 AE 3%, respectively, followed by 43 AE 1% for cysteine. Thermal decomposition led to near-complete recovery of NO based upon the quantification of the RSNO formation for each nitrosated polymer. Our ability to exert control over the thiol structure, extent of incorporation and the subsequent nitrosation is crucial to the resulting range of NO release kinetics that were yielded. The functional utility of these materials is demonstrated in that these non-toxic polymers release NO under physiological conditions, have degradation profiles that are appropriate for tissue scaffolds and can be prepared as electrospun nanofibers, commonly used in tissue and bone regeneration applications.

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A systematic and comprehensive summary of various TNS-based biomedical research with a special emphasis on drug-delivery, tissue engineering, biosensor, and anti-bacterial applications.

Many common wound healing aids are created from biodegradable polymeric materials. Often, these materials are unable to induce complete healing in wounds because of their failure to prevent infection and promote cell growth. This study reports the development of therapeutic materials aimed at overcoming these limitations through the release of a naturally occurring antimicrobial agent from a porous, polymeric fiber scaffold. The antimicrobial character was achieved through the release of nitric oxide (NO) while the porous structure was fabricated through electrospinning polymers into nanofibers. Three variations of the polymer poly(lactic-co-glycolic-co-hydroxymethyl propionic acid) (PLGH) modified to include thiol and NO groups were investigated. Fibers of the modified polymers exhibited smooth, bead free morphologies with diameters averaging between 200 and 410 nm. These fibers were deposited in a random manner to create a highly porous fibrous scaffold. The fibers were found to release NO under physiological pH and temperature and have the capacity to release 0.026 to 0.280 mmol NO g(-1). The materials maintained their fibrous morphological structure after this exposure to aqueous conditions. The sustained morphological stability of the fiber structure coupled to their extended NO release gives these materials great potential for use in wound healing materials.

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