Development of a wireless platform to generate nitric oxide for implanted biomedical devices

The perturbation of homeostatic mechanisms caused by interactions between any indwelling biomedical device and the biological medium into which it is implanted initiates a dynamic wound healing response from the host which can be rigorous and ongoing. The typical result of this response is a severe degradation in the performance and safety of the device, often to the extent of precluding their clinical use. Nitric oxide (NO) is an endogenously produced biomolecule capable of mediating many of the cellular processes leveraged against implanted devices. The in vivo performance of indwelling devices prepared with NO release coatings has recently been evaluated with very encouraging results. This work developed a platform capable of both generating programmable fluxes of NO and directly evaluating the performance of indwelling probes under different profiles of NO generation. This platform can be used to improve the efficacy of NO release materials in mitigating the host response.

Development of Vapor Deposited Silica Sol-Gel Particles for a Bioactive Materials System to Direct Osteoblast Behavior

Tissue engineering and regenerative medicine have emerged in an effort to generate replacement tissues capable of restoring native tissue structure and function, but because of the complexity of biologic system, this has proven to be much harder than originally anticipated. Silica based bioactive glasses are popular as biomaterials because of their ability to enhance osteogenesis and angiogenesis. Sol-gel processing methods are popular in generating these materials because it offers: 1) mild processing conditions; 2) easily controlled structure and composition; 3) the ability to incorporate biological molecules; and 4) inherent biocompatibility. The goal of this work was to develop a bioactive vaporization system for the deposition of silica sol-gel particles as a means to modify the material properties of a substrate at the nano- and micro- level to better mimic the instructive conditions of native bone tissue, promoting appropriate osteoblast attachment, proliferation, and differentiation as a means for supporting bone tissue regeneration. The size distribution, morphology and degradation behavior of the vapor deposited sol-gel particles developed here were found to be dependent upon formulation (H2O:TMOS, pH, Ca/P incorporation) and manufacturing (substrate surface character, deposition time). Additionally, deposition of these particles onto substrates can be used to modify overall substrate properties including hydrophobicity, roughness, and topography. Deposition of Ca/P sol particles induced apatite-like mineral formation on both two- and three-dimensional materials when exposed to body fluids. Gene expression analysis suggests that Ca/P sol particles induce upregulation osteoblast gene expression (Runx2, OPN, OCN) in preosteoblasts during early culture time points. Upon further modification-specifically increasing particle stability-these Ca/P sol particles possess the potential to serve as a simple and unique means to modify biomaterial surface properties as a means to direct osteoblast differentiation.