Drug delivery using thermo-responsive poly (N-isopropylacrylamide) based hydrogel and human osteo-sarcoma (HOS) cell adhesion on biomaterials

This dissertation presents the results obtained from recent experimental, theoretical and computational studies of drug delivery and cell adhesion in bio-micro-electro-mechanical systems (BioMEMS). These include: drug delivery device design and fabrication, the characterization of thermo-responsive poly (N-isopropylacrylamide) (PNIPA) based hydrogels, shear assay measurements, and cell alignment on micro-textured polydimethylsiloxane (PDMS).;A novel drug delivery device, with micro-channels and a coated heater layer, was designed and fabricated using photolithography techniques. The device employs thermo-responsive poly(N-isopropylacrylamide) (PNIPA) based hydrogels for controllable localized drug release. Thermo-responsive hydrogel (PNIPA) is modified with comonomer acrylamide (AAm) to increase the lower critical solution temperature (LCST) and sodium alginate (SA) to improve the swelling and diffusion performance. Trypan blue release is measured under different temperature control. Numerical studies show strong concentration dependent diffusion kinetics for drug release from the hydrogel. The coupled moving boundary problem during the diffusion process is also carefully simulated. The implications of the results are assessed for cell biophysics, and potential applications in implantable BioMEMS.;Human osteosarcoma (HOS) cells are cultured in vitro on selected biomaterials surfaces that are relevant to implantable biomedical systems. The interfacial strengths between single cancer cells and biocompatible materials are measured under shear flow. A combination of 3D in-situ confocal image reconstruction and computational fluid dynamics simulations are used to determine the interfacial strengths. Immuno-fluorescence staining reveals the sub-cellular adhesion between focal adhesion proteins and extra-cellular matrix (ECM) proteins. The spreading, alignment and integration of cells are also studied on micro-textured PDMS surfaces with systematic changes in groove height and spacing. The results obtained are related to cell mechanics, with applications in cancer cell detection and the integration of implantable devices with biological tissue.