TiO2 Nanotubes for Drug Delivery and Vascular Tissue Engineering

The purpose of this project is to investigate how TiO2 nanotube arrays interact with small molecules, proteins, and cells for local drug delivery and vascular applications. In this first part of this project, TiO2 nanotubes of various dimensions were used to elute albumin, a large protein molecule, as well as sirolimus and paclitaxel, common small molecule drugs. The nanotubes controlled small molecule diffusion for weeks and large molecule diffusion for a month. Drug eluted from the nanotubes was bioactive and decreased cell proliferation in vitro. Elution kinetics was most profoundly affected by tube height. This study demonstrates that TiO2 nanotubes may be a promising candidate for a drug-eluting implant coating.To investigate the effects of nanotubular titanium oxide (TiO2) surface on vascular cells, endothelial (EC) and vascular smooth muscle cells (VSMCs) were cultured on TiO2 nanotube arrays. Vascular cell response to nanotubes was investigated through immunofluorescence staining, scanning electron microscopy, 5-ethynyl-2′-deoxyuridine proliferation assays, and prostaglandin I2 (PGI2) enzyme immunoassays. We found that the nanotubular surface significantly enhances EC proliferation and secretion of PGI2. The surface also results in a decrease in VSMC proliferation and increased expression of smooth muscle α-actin. These data suggest that engineered nanotopographical cues may influence both EC and VSMC behavior in a manner that may be useful for stent or other vascular applications. To investigate this further, the response of primary human endothelial (ECs) and vascular smooth muscle cells (VSMCs) to TiO2 nanotube arrays is studied through gene expression analysis. Microarrays revealed that nanotubes enhanced EC proliferation and motility, decreased VSMC proliferation, and decreased expression of molecules involved in inflammation and coagulation in both cell types. Networks generated from significantly affected genes suggest that cells may be sensing nanotopographical cues via pathways previously implicated in sensing shear stress