New Frontiers in Biomedical Systems: From Bioinspired Design to BioMEMS and Nanotechnology Wole Soboyejo Princeton Institute of Science and Technology of Materials And Department of Mechanical and Aerospace Engineering Princeton University Princeton, NJ
Acknowledgments • Glaucio Paulino (UIUC) • Dulce Rufino • Ken Chong (NSF) • Jorn Larsen-Basse (NSF) • Carmen Huber (NSF)
Acknowledgments • Challa Kumar (LSU/CAMD) • Carolla Leuschner (Pennington Biomedical) • Warren Warren (Princeton) • Sylvia Centano (Princeton) • Dr. Jikou Zhou (Princeton) • Dr. Min Huang (Princeton) • Chris Milburn (Princeton) • Steve Mwenifumbo (Princeton/Cambridge) • Lauren Hayward (Princeton) • Lara Ionescu (Princeton) • Omar Bravo (University of Puerto Rico) • Robert Bond (West Windsor/Plainsboro)
Outline of Presentation • Background and Introduction • Bioinspired Design of FGMs • BioMEMS – Implantable BioMEMS Structures • Nano-Bio-Technology – Functionalized Nanoparticles for Cancer Cell Detection • Summary and Concluding Remarks
Background and Introduction • Biomedical design is often done without adequate inputs from biology • Examples – dental implants that fail after a few years - BioMEMS and nano-structures from non- biocompatible materials • Objective is to introduce some basic ideas in biomedical design at different scales
MECHANICAL PROPERTIES OF DENTAL MATERIALS/MULTILAYERS Dental ceramic E: 50~200 GPa Dental cement E=5 GPa Dental restoration Dentin-like polymer E=20 GPa Enamel E=65 GPa Dentin-Enamel Junction (DEJ): Graded Tooth Structure Dentin E=20 GPa
ELASTIC MODULUS DISTRIBUTION IN DENTIN-ENAMEL JUNCTION (DEJ) Marshall et al. J Biomed Mater Res 54, 87-95, 2001
MAXIMUM PRINCIPAL STRESS DISTRIBUTION Dental Restoration Natural Tooth E=65 GPa E=65 GPa E=20 GPa E=20 GPa 1 mm 1 mm
MAXIMUM PRINCIPAL STRESS ceramic cement polymer Maximum Principal Stress (MPa) 140 Zircornia Empress 2 Glass 120 Dicor Mark II 100 80 60 FGM Dicor MGC ceramic 40 Graded ceramic/polymer 20 polymer 0 0 50 100 150 200 250 Elastic modulus of ceramic (GPa)
DIFFERENT YOUNG’S MODULUS DISTRIBUTION E=72 GPa E=20 GPa Max principal stress (MPa) Young’s modulus (GPa) 55 80 50 70 I 60 45 II 50 III 40 40 IV 35 30 V 30 20 25 10 20 0 I II III IV V 0 20 40 60 80 100 Cement thickness (µm) Different Young’s modulus distribution
Introduction to BioMEMS Systems BioMEMS structures are micron-scale devices that are used in � biomedical or biological applications At this scale, a wide range of devices are being made (e.g. pressure � sensors, drug delivery systems, and cantilever detection systems) Explosive growth in emerging markets – civilian and military � applications expected to reach multi-billion dollar levels Implantable Blood Drug Delivery System Pressure Sensor
Biocompatibility of Silicon MEMS SystemS Si is not the most biocompatible material � Can be made biocompatible through the use of polymeric or Ti � coatings. Polymeric coatings used on Si drug release systems. � Ti coating approaches are also being developed. � Coated BioMEMS Structure 500 nm Ti Layer on Si Ti Ti Ti Si Ti 500 nm
SURFACE CHEMISTRY – CELL SPREADING HOS Cells Si Si - 50 nm Titanium 30 minutes 60 minutes 120 minutes
PROTEINS INVOLVED IN ADHESION Adhesion between � cells/substrate surfaces - focal contacts or adhesion plaques. Consist of integrins, � microfilaments, and proteins. Integrins bind to the � extracellular matrix or cell surface. Connected by proteins to the microfilaments (actin cytoskeleton). � Talin and vinculin -two main proteins responsible for this connection. �
ADHESION - IMMUNO-FLUORESCENCE (IF) STAINING Actin IF staining - used to view focal � adhesions (actin and vinculin). Tagged anti-bodies bind to specific � protein of a cell. Focal adhesions of specific cells can � be quantitatively measured. Vinculin Qualitative assessment of cell � alignment and growth can be achieved on a multi-cell scale (contact guidance). Schwarzbauer et. al , 2002
Cell Attachment on PS/Ti Surfaces Cell Spreading on PS/Ti Surface 3D View of Attached Cell
SHEAR ASSAY MEASUREMENT OF CELL ADHESION Shear Flow Schematic Shear stress for detachment is � given by 6Q µ τ = wh 2 Where Q - flow rate & µ -dynamic � Cell Detachment viscosity Considering initial onset of � detachment to correspond to “adhesion” strength: � τ = 70 Pa Polystyrene (PS) � τ = 81 Pa Ti Coated PS
Shear Assay Results Shear Stress at detachment for 2 Day HOS cultures Determined as wall shear stress given by: Q µ 6 τ = 2 wh Material Adhesion Strength (Pa) Material Adhesion Strength (Pa) Polystyrene 70 Ti-Coated Polystyrene 81 Silicon 82 Ti-Coated Silicon 104
Micro-Groove Geometry and Cell/Surface Interactions • Cells can undergo contact guidance when in contact with micro- grooved geometries • This depends on the size of the grooves relative to the size of the cells • Contact guidance has implications for wound healing and scar tissue formation 2 µ m Micro-Grooves 12 µ m Micro-Grooves Cell Cell 100 µ m 30 µ m
MEMS-Enhanced Trileaflet Valve
Our Approach to Early Cancer CAMD Detection and Treatment! LP conjugates LP conjugates LP conjugates LP conjugates LP conjugates LP conjugates LP conjugates LP conjugates Magnetic core LHRH LHRH LHRH LHRH LHRH LHRH LHRH LHRH Polymer shell with lytic peptide conjugates
CAMD Wet Chemical Synthesis of Nano-particles Metallic, polymeric and metal-polymer Nano-particles using bottom-up approaches Novel Micro reactor technology for scale-up and controlled synthesis Synchrotron radiation based X-ray absorption Spectroscopic characterization Capability to attach bio-molecules
Nanoparticles in tumor: Prussian blue Used to Stain Paraffin Embedded Histological Sections
CAMD Targeted Destruction of Prostate Cancer in Balb/c athymic nude mice PC-3.luc Xenograft bearing male nude mice were used LHRH bound nanoparticles effectively bind to tumor Use of Nano-LHRH results in accumulation 68% of nanoparticles in tumor Distribution of iron in other tissues is being mapped
TEM Imaging of Cancer LHRH-SIOP in Tumor SIOP in Tumor
Fundamentals of Magnetic Resonance Imaging (MRI) • Hydrogen atoms in water have a property called spin • MRI generates a magnetic pulse that aligns all of the spins in a certain direction • The magnetic resonances of the nuclei will cause differences in how they return to their normal spin state • The MRI machine records the energy released as they realign at different times and generates an image • A set of images are generated at certain small time intervals after the pulse sequence
Initial MRI Experiments: Cherry Tomato and Grape • Injected grapes with saturated The iron creates a magnetic field saline solution of nanoparticles in the water, thus creating a • Observed contrast at the location blind spot (dark) for the MRI of the injection (nanoparticles)
MRI Imaging of Cancer
MRI Imaging of Cancer – multiCRACED Magnetic Anisotropy
Summary and Concluding Ramarks • Overview of some recent work on bio-inspired design, bioMEMS and bionanotechnology • Bioinspired FGM design proposed for crown/dentin interface (need to fabricate structures & test idea) • Nano-scale titanium coatings designed for implantable biocompatible BioMEMS structures • LHRH-coated magnetite particles provide opportunities for early detection of breast & prostate cancer • Significant opportunities for mechanics and materials research – modeling, adhesion, detection of cancer • We welcome your involvement in the ongoing Americas program (americas.princeton.edu – no www)
Recommend
More recommend
