Shoffstall Lectures 1-3 Selected Slides PDF

EBME 306 Overview Goal: Learn The Fundamentals Needed to Understand Tradeoffs in Device Design Introduction to Biomaterials Biocompatibility, Tissue Response Bio aspect of BIOmaterials Inflammation Immunology and Infection Blood Compatibility Material Selection / Design Materials aspects of bioM...

EBME 306 Overview Goal: Learn The Fundamentals Needed to Understand Tradeoffs in Device Design Introduction to Biomaterials Biocompatibility, Tissue Response Bio aspect of BIOmaterials Inflammation Immunology and Infection Blood Compatibility Material Selection / Design Materials aspects of bioMATERIALS StructureFunction Material Properties Scale NanoMacro Polymers Breadth / Expertise Protein-Material, Cell-Material Interactions Fundamentals of Interface Neural Orthopedic Blood Applications Tissue Engr. Shoffstall Presentation Name Drug Delivery Other October 14, 2015 1 Tunicates Sea Cucumber Giant Squid Beak Mosquito Nature Inspired Materials, Biomimicry, Examples in Devices and Research Material Selection / Design EBME 306 Pre-Recorded StructureFunction Material Properties Scale NanoMacro Biomimetic vs Bio-Inspired Biomaterials Biomimicry: match the natural subject as closely as possible. Bioinspiration: leverages materials, methods, or other cues from nature and applys them toward analogous functions to enhance an engineered system. Example from Neural Context Shoffstall & Capadona (2018) Current Opinion in Biomedical Engineering Shoffstall Presentation Name October 14, 2015 3 Common Biomimetic Approaches (Neural Context) Implanted devices are mechanically, chemically, or electrically altered to exhibit similar properties to the natural neural environment. Features in the brain are small and mechanically pliant (Physical). Proteins are the first molecules to react to device implantation and their conformation determines downstream effects (Chemical). Neural tissues are excitable by ionic currents (Electrical). Ultimately, the brain is a dynamic, living environment. Permanent synthetic structures are more likely to cause inflammation and damage over time. Living systems have the advantage of being able to dynamically respond to a changing environment. Mechanical Chemical Electrical Living / Dynamic  Bulk Stiffness & Flexibility  Managing the Protein Corona  Ionic Conductors  Cell-Seeded Scaffolding  Surface Topography  Bioactive Surfaces  Flexible Conductors  Tissue Ingrowth / Remodeling  Size & FormFactor  Antioxidants & Free-Radical Scavengers  Electrically Responsive Materials  Biodegradable Systems Shoffstall & Capadona (2018) Current Opinion in Biomedical Engineering Shoffstall Presentation Name October 14, 2015 4 Ceramics Proteins Polymers Carbohydrates Metals From Atoms to Bulk Materials: Understanding the “Materials” aspect of Biomaterials Material Selection / Design EBME 306 10/2/2019 StructureFunction Material Properties Scale NanoMacro Shoffstall Presentation Name October 14, 2015 6 Park and Lakes Material Properties Structure (atomic, nano, micro, macro)  Function Some of the Most Important for Medical Applications • • • • • • • • • • • Acoustical properties Atomic properties Chemical properties Electrical properties Environmental properties Magnetic properties Manufacturing properties Mechanical properties Optical properties Radiological properties Thermal properties Shoffstall Presentation Name • • Chemical properties (ALL!!!) Electrical properties (Neuromodulation, Stimulation) • • • • • • Magnetic properties (MRI compatibility) Manufacturing properties (ALL, Processing) Mechanical properties (Orthopedic Implants) Optical properties (Contact Lenses) Radiological properties (Intraoperative Imaging) Thermal properties (Ablation, RF Heat Dissipation) October 14, 2015 7 Biomaterials Natural Materials proteins: collagen, fibrin, elastin polysaccharides: alginate, chitosan, glycosaminoglycans (hyaluronic acid), cellulose De-cellularized scaffolds Lipids Advantages • biofunctionality • biodegradable • less inflammation Disadvantages • mechanical properties • stability • processing • immunogenicity Shoffstall Presentation Name Synthetic Materials polymers: polyurethanes, PTFE, PE, polysiloxanes, poly(a-hydroxy)esters (PLA/PGA), PCL, pHEMA ceramics/glasses: HA, bioactive glasses metals: Ti/Ti-alloys, Co-Cr alloys, stainless steel Advantages • property “tuning” • processing Disadvantages • loss of cell function • inflammation * Note, this is not an exhaustive list: examples of most common types used in medical devices October 14, 2015 8 Ceramics Ceramics are nonmetallic and inorganic solids; atoms are ionically bonded. • • • • • Ceramics High melting points (so they're heat resistant). Great hardness and strength. Considerable durability (they're long-lasting and hard-wearing). Low electrical and thermal conductivity (they're good insulators). Chemical inertness (they're unreactive with other chemicals). Metal …but they are very brittle Ceramic https://www.explainthatstuff.com/ceramics.html Shoffstall Presentation Name October 14, 2015 9 H-bond Reactivity, bonds, functional groups, analysis tools, and examples of structure-property correlations across scales Material Selection / Design EBME 306 10/4/2019 StructureFunction Material Properties Scale NanoMacro 11 Biomaterials Overview Synthetic Materials polymers ceramics metals Structure (order) properties processing They all influence each other How is the function of the material determined? STRUCTURE / COMPOSITION • • • • • Advantages property “tuning” processing Disadvantages loss of cell function inflammation mechanical properties Chemistry determines EVERYTHING!!! Shoffstall Presentation Name October 14, 2015 11 12 Atoms  Bonds Primary Bonding (Strong Interactions): Ionic bond = electrostatic forces between oppositely charged ions (transfer of electrons) • Form packed crystalline structures to stabilize charges, Brittle and Hard  ceramics Covalent bond = sharing of valence electrons (directionally) between two atoms; usually non-metallic atoms • strong directional bonds, polymers, organics, all functional groups Metallic bond = sharing of valence electrons (non-directionally) between groups of atoms in 3-D • Conductivity  metals Shoffstall Presentation Name October 14, 2015 12 13 Secondary Bonding (Weak Interactions intermolecular): Hydrogen bonding Hydrophobic Effect Van der Waals ion-dipole / dipole-dipole London Dispersion (instantaneous dipole) Shoffstall Presentation Name October 14, 2015 13 Dislocation motion Fig. 3.6 in textbook Metals Ceramics + - + - - + - + + - + - + Slip - deformation - + - not in polymers, not likely in ceramics, common in metals Allows plastic deformation without breaking an entire plane of atoms at once, ductility 14 Shoffstall Presentation Name October 14, 2015 14 15 Few materials are pure single crystals… Polycrystalline materials: Materials with many crystals. Each crystal is a separate grain within the material…  different slip systems all work simultaneously Dislocations: can transit across grain boundaries, but very difficult. GENERALLY, the more grain boundaries, the more dislocations and thus plastic deformation are hindered = increased strength. Shoffstall Presentation Name October 14, 2015 15 MOST IMPORTANT TAKE HOME POINT!!! All materials are used in their linear proportional range – no deformation or destruction of the materials has taken place. Shoffstall Presentation Name October 14, 2015 16 Some Other Useful Surface Characterization Techniques! Note the tradeoffs: depth, spatial resolution and cost Biomaterials Science: An Introduction to Materials in Medicine, Ratner Ed. Shoffstall Presentation Name October 14, 2015 17 Surface Energy Young’s Equation: Shoffstall Presentation Name October 14, 2015 18 Relate to 356 Thermodynamic Methods for Surface Analysis: Contact Angle and Wettability The contact angle (θC) is the angle at which a fluid interface meets a solid surface and can be easily illustrated by the shape of a fluid drop sitting on a horizontal flat solid surface Thermodynamic (energy) equilibrium between three phases (gas/air, liquid and solid) at the interface is described by Young’s equation: Measurement of θC provides a way to measure interfacial energy and provides information about “wettability” (hence hydrophilicity) of the surface. θC < 90o is hydrophilic while θC > 90o is hydrophobic Shoffstall Presentation Name Hydrophobic October 14, 2015 Intermediate Hydrophilic 19 Surface Chemistry by FTIR-ATR Analysis of Bonds Depth of analysis (>0.5 mm) depends on refractive index of ATR scanning element. Get more information than ESCA but is less surface sensitive Shoffstall Presentation Name October 14, 2015 20 X-ray Photoelectron Spectroscopy (XPS) Also called Electron Spectroscopy for Chemical Analysis (ESCA) Impingement of X-ray results in release of core electron as ‘photoelectron’ (~1-10 nm depth) whose Kinetic Energy and hence Binding Energy can be measured and mapped to the parent element/atom Very useful for elemental analysis of polymer surfaces and coatings Shoffstall Presentation Name October 14, 2015 21 22 XPS Shoffstall Presentation Name SEM & XRD October 14, 2015 22 Light Microscopy traditional brightfield darkfield phase contrast fluorescence (normal and confocal) Good for analyzing samples at micron level resolution Good for cell-material analysis since most cells are in the micron range Textbook p. 253 Shoffstall Presentation Name October 14, 2015 23 Examples of Light Microscopy Analysis Brightfield Darkfield Confocal fluorescence microscopy of a polymer scaffold shows poor ultrastructural resolution Fluorescence Shoffstall Presentation Name Phase contrast showing RBC interacting with fibrin October 14, 2015 24 Ultrastructure of Biomaterials by TEM Shoffstall Presentation Name October 14, 2015 25 Scanning Electron Microscopy (SEM) Sample surface is bombarded with electrons (usually from a heated Tungsten source) having moderate to high energy (few hundred eV to ~ 50 keV) in a condensed zone (1-5 nm in focal spot dia) The primary electron bombardment excites and emits secondary and backscattered electrons from atoms in a small area extending from 100 nm5 μ into the sample surface. The emitted electrons are detected as an “area map” (micrograph) of the characteristic bombarded region. Shoffstall Presentation Name October 14, 2015 26 Scanning Probe Microscopy (SPM) Very good for surface profiling/ultrastructure/surface interaction analysis The three most common scanning probe techniques are: Atomic Force Microscopy (AFM) measures the interaction force between the tip and surface. The tip may be dragged across the surface, or may vibrate as it moves. The interaction force will depend on the nature of the sample, the probe tip and the distance between them. Scanning Tunneling Microscopy (STM) measures a weak electrical current flowing between tip and sample as they are held a very small distance apart. Near-Field Scanning Optical Microscopy (NSOM) scans a very small light source very close to the sample. Detection of this light energy forms the image. NSOM can provide resolution below that of the conventional light microscope. Shoffstall Presentation Name October 14, 2015 27 Atomic Force Microscopy (AFM) Cantilever : ~ 100 mm long Tip: ~ 4 mm dia at cantilever interface and ~ 20-40 nm dia at apex Mode of Operation Force of Interaction contact mode strong (repulsive) - constant force or constant distance non-contact mode weak (attractive) - vibrating probe lateral force mode frictional forces exert a torque on the scanning cantilever magnetic force the magnetic field of the surface is imaged thermal scanning the distribution of thermal conductivity is imaged Shoffstall Presentation Name October 14, 2015 28