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Questions and Answers
What is the definition of a biomaterial?
What is the definition of a biomaterial?
Define bioinert as related to biomaterials.
Define bioinert as related to biomaterials.
Bioinert biomaterials are materials that the body largely ignores, and this was a primary goal in biomaterial design until recent years.
Polymerization process involves combining __________ into a polymer.
Polymerization process involves combining __________ into a polymer.
monomers
Match the following classification of polymers with their descriptions:
Match the following classification of polymers with their descriptions:
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What are some uses of metals in biomaterials?
What are some uses of metals in biomaterials?
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Which of the following are physical properties of metals? Select all that apply.
Which of the following are physical properties of metals? Select all that apply.
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Point defects in crystal structures involve only one or two atoms.
Point defects in crystal structures involve only one or two atoms.
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Solid state diffusion is the movement of atoms due to thermal __________.
Solid state diffusion is the movement of atoms due to thermal __________.
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Match the following material strengthening mechanisms with their descriptions:
Match the following material strengthening mechanisms with their descriptions:
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What does Anoikis refer to?
What does Anoikis refer to?
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Which of the following are components of the innate immune system defense?
Which of the following are components of the innate immune system defense?
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Elastin is the most elastic protein and can last for decades.
Elastin is the most elastic protein and can last for decades.
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What is the primary function of fibroblasts? They are responsible for the synthesis of ________.
What is the primary function of fibroblasts? They are responsible for the synthesis of ________.
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Match the following cell-cell contact types with their descriptions:
Match the following cell-cell contact types with their descriptions:
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What is mechanosignaling?
What is mechanosignaling?
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What are the methods of mechanosignaling?
What are the methods of mechanosignaling?
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What is a hydrogel?
What is a hydrogel?
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Match the crosslinking types with their descriptions:
Match the crosslinking types with their descriptions:
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Intra-molecular forces are stronger than intermolecular forces.
Intra-molecular forces are stronger than intermolecular forces.
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Why does surface tension occur?
Why does surface tension occur?
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Study Notes
Biomaterials
- Definition: A material that can function as a whole or part of a system which augments, repairs, or replaces any tissue or organ system.
- Examples: knee/hip implants, contact lenses, dental implants, 3D printed tissues, heart valves, skin grafts, hearing aids, hair implants, stents, eyeballs, and prosthetics.
Classification of Biomaterials
- Metals: Metallic bonding (sea of electrons), sharing of free electrons. Examples: iron, gold, silver.
- Ceramics: Ionic bonding, non-directional, electrons are taken from the outer level. Examples: salt, silica/sand, alumina, hydroxyapatite.
- Polymers: Covalent bonding, directional, electrons are shared. Examples: PEG, hyaluronic acid.
Properties of Biomaterials
- Mechanical: includes stiffness, soft, hard, viscoelasticity.
- Chemical: NMR, Raman spectroscopy, Fourier-transform infrared spectroscopy.
Equations
- Stress: σ = F/A
- Strain: ε = Δl/lo
Polymers
- Definition: many units, larger macromolecule.
- Polymerization: combining monomers (repeat unit) into a polymer.
- Types of polymerization:
- Addition: chain polymerization, no by-products.
- Condensation: step polymerization, water is a byproduct.
- Examples of common polymers:
- Polyester
- Polyether
- Polyanhydride
- Polyamide
- Polyurethane
- Polyurea
Polymer Weight
- Molecular weight
- Polydispersity: shows how uniform the population of polymers are.
- Monodisperse: ideal polymer, small polydispersity.
- Polydisperse: large polydispersity.
Classification of Polymers
- Thermoplastic: polymers that flow more easily when squeezed, pushed, or stretched.
- Thermoset: polymers that flow and can be molded initially, but their shape becomes set upon curing.
- Elastomer: polymers that are elastic like rubbers.
Copolymers
- Random: uncontrolled order, randomly positioned.
- Alternating: one after the other in a pattern.
- Block: large blocks alternate.
- Graft: chains of one polymer grafted onto the backbone of another polymer.
Polymer Structures
- Linear: in terms of packing, linear can be more densely packed.
- Branched: has a variety of branching.
- Cross-linked: still has points of connection.
- Network: has many points of connection.
- Order of strength: branched < linear < cross-linked < network.
Polymer Crystallinity
- Chain folded structure.
- Linear polymers can form ordered repeating regions of crystal.
Natural vs Synthetic Polymers
- Natural: examples are gelatin, proteins, zein, hyaluronic acid, mucin.
- Protein synthesis: an example of condensation polymerization.
Protein Classification
- Globular, membrane bound, fibrous.
Levels of Protein Structure
- Primary: sequence of amino acids.
- Secondary: includes alpha helix and beta sheets.
Degradation Types
- Surface erosion: poly(ortho)esters and polyanhydrides, most water sensitive.
- Bulk degradation: PLA, PGA, PLGA, or PCL, faster than surface erosion.
Biodegradable Polymers
- Broken down by hydrolysis.
- Rate of erosion is determined by chemical bond stability, hydrophobicity, and morphology.
PEGylation
- Increases drug size, reduces hydrophobicity, and increases stability.
- Widely used in drug modification and protein therapeutics.
Bioconjugation
- Attachment of one molecule to another, usually through a covalent bond.
Immunocytochemistry
- Detection and visualization of proteins, including immunohistochemistry, immunofluorescence, and immunocytochemistry.
Amino Acids
- Sites for potential conjugation.
- Functional groups: amine, carboxyl, thiol, alcohol.
Orthopedics
- Fixture vs replacement: fixture stops movement, replacement replaces function/movement.
- Osteoconductive: enables integration of new bone with the host bone.
- Osteoinductive: promotes new bone growth.
Properties of Orthopedic Implants
- No toxicity.
- Suitable for mechanical strength.
- High wear resistance.
- Minimize stress shielding.
- Osseointegration abilities.
Corrosion
- Process that transfers electrons from one substance to another.
- Mechanism: in acidic and neutral environments.
- Prevention: avoid using combinations of metals, use metals with similar nobility, and use passive methods.
Suitable Mechanics
- Cyclic loading: material needs to withstand years of repeated loading.
Wear Resistance
- Aseptic loosening: joints and orthopedics damage over time.
Stress Shielding
- Creates osteopenia: decrease in bone density.
Osseointegration
- Formation of a direct interface between an implant and bone without intervening soft tissue.
Metals
- Uses: bone and joint replacement, dental implants, facial reconstruction, cardiovascular devices, external prostheses, surgical instruments.
Properties of Metals
- Physical: luster, good conductors of heat and electricity, high density, high melting point, ductile, malleable.
- Chemical: easily lose electrons, surface reactive, loss of mass, change in mechanical properties.
Crystal Structures
- Unit cell: the smallest repeating unit within a crystal lattice.
- BCC, FCC, and HCP structures.
Metal Processing
- Casting: contained nucleation starts at the edge.
- Formation of crystals: nucleation, growth, and grain boundaries.
Crystal Defects
- Point defects: one or two atoms.
- Solid solution: normal crystal structure is maintained with impurity.
Rules for Solid Solution
- Size difference should be within 15%.
- Electronegativities should be similar.
- Valence charges should be similar.
- Crystal structures should be the same.
Solid State Diffusion
- Movement of atoms due to thermal energy.
- Through diffusion, atoms can move to select locations.
Strengthening Mechanisms
- Grain size reduction: improves toughness.
- Solid solution strengthening: increases strength.
- Strain hardening: ductile metals become stronger when deformed plastically.
- Recovery-annealing: relieves internal strains, reduces dislocations, and makes metal weaker.
Ceramics
- Uses: orthopedic implant, coatings and thin films, bone cements, scaffolds and bone grafts, dental screws, porous scaffolds.
Properties of Ceramics
- Generally inert.
- Resists chemical reactivity.
- Strong.
- Sensitive to deformation.
- Advantages: inert, wear-resistant, high modulus, and compressive strength.
- Disadvantages: brittle, low fracture resistance, poor fatigue resistance.
Structures
- Crystalline ceramic: long-range order, organized structure of grains.
- Glassy ceramic: short-range order, typically do not form grains.
- Glass-ceramics: combination of crystalline grains surrounded by amorphous material.
Pauling's Rules
- Magnitude of charge: ceramic crystals are neutral.
- Relative size of the ions: cations typically smaller.
Crystal Structure
- Larger the cation is relative to the anion, the more anions that surround it.
- Coordination number and ratio of cation radius to anion radius.
Linear Defects
- Edge dislocation: occurs when there is termination of a plane of atoms in a crystal.
Bio ceramic-tissue Interaction
- Morphological fixation: dense, inert, nonporous ceramics attach to bone.
- Biological fixation: porous inert ceramic attaches by bone growth.
- Bioactive fixation: dense, non-porous surface-reactive ceramics attach directly to bone.
Types of Bio ceramics
- Bioinert: stable and non-reactive.
- Bioactive: direct bone implant bond.
- Bioerodible: gradual degradation.
Material Characterization
- Types of forces: tension, compression, shear, torsion.
- Stress and strain.
- Elastic deformation: linear, reversible strain.
- Plastic deformation: non-linear, irreversible strain.
- Viscoelastic: viscous liquid + elastic solid-like.
Time-dependent Properties
- Creep: plastic deformation of material under constant load over time.
- Stress relaxation: decrease in stress over time under constant strain.
Viscoelastic Behaviors
-
Why stiffness and viscoelasticity matter: important for biomaterials because they mimic tissue.### Cellular Morphology and Development
-
Viscoelasticity drives cellular morphology and development, including stem cell division and differentiation.
Surface Analysis Techniques
- Contact angle analysis:
- Hydrophilic: θ < 90°
- Hydrophobic: θ > 90°
- Superhydrophobic: θ > 150°, typically requires texture
- Single point: equilibrium between liquid droplet and solid surface has been reached
- Dynamic contact angle:
- Advancing angle: contact angle of the liquid with dry surface
- Receding angle: contact angle with the water-absorbed surface
Microscopy Techniques
- Optical microscopy:
- Advantages: low magnification, quick, non-destructive, color differentiation available
- Disadvantages: limited resolution, smaller depth of field, light reflections can mask certain features
- Scanning Electron Microscopy (SEM):
- Advantages: greater depth of field, high magnification, sub-nanometer resolution available
- Disadvantages: slower inspection time, grayscale only
- Transmission Electron Microscopy (TEM):
- Advantages: create higher resolution images, allow users to examine more characteristics of a sample, higher magnification
- Disadvantages: more expensive, slower speed, more complicated operation
- Scanning probe microscopy → atomic force microscopy (AFM):
- AFM: uses Van der Waals forces to promote interaction of a cantilever tip with the surface, scanning across the surface gives atomic detail of the topography
Spectroscopy Techniques
- X-ray photoelectron spectroscopy (XPS)
- Fourier transform infrared spectroscopy (FTIR):
- Measures vibrational modes in molecules with infrared light (stretching, twisting, scissoring, rocking, wagging)
- Matrix assisted laser desorption ionization (MALDI) mass spectrometry:
- Laser desorption of material on a surface complexed with ionizable small molecules (the matrix)
- Secondary ion mass spectrometry (SIMS):
- Useful technique for measuring the composition of a material
- Ions are shot at a sample, stripping off the surface layer of material, and these secondary ions are then analyzed using MS principles
Biological Characterization
- Analytical techniques:
- Types of assays:
- Scratch assay (wound healing assay): measures a cell's ability to close the wound
- MTT Assay: measures metabolism, reduction potential
- PicoGreen assay: measures cell quantity by quantifying DNA amount
- Alamar Blue Assay: measures cell viability and proliferation
- Live/Dead Assay: simultaneous determination of live and dead cells
- BrdU Assay: shows cell division, incorporates BrdU into the cell's DNA
- Generic cell division assay: measures cell division
- Types of assays:
Cell Death and Inflammation
- Anoikis: death due to lack of cell-matrix interactions
- Apoptosis: programmed cell death
- Necrosis: chaotic cell death
- Autophagy: recycle components
- Inflammation:
- 4 main components of the innate immune system:
- Anatomic barriers: skin, mucus membranes
- Physiological barriers: temperature (37°C)
- Phagocytic cells: engulf, granulocytes → neutrophils, monocytes → macrophages
- Acute inflammation
- 4 main cardinal signs of inflammation:
- Rubor (redness)
- Tumor (swelling)
- Calore (heat)
- Dolore (pain)
- Common cells involved in inflammation:
- Granulocytes: family of cells that can phagocytose foreign invaders
- Monocytes: phagocytic capability
- Macrophages: monocytes that have migrated or been born within a tissue
- Megakaryocytes: break apart to form platelets
- 4 main components of the innate immune system:
Blood-Material Interactions
- When a biomaterial is put into the body:
- Injury
- Blood-biomaterial interaction
- Provisional matrix formation
- Acute inflammation
- Chronic inflammation
- Granulation tissue
- Foreign body response
- Fibrous capsule formation
- Sequence of events:
- Biomaterial implantation
- Protein adsorption
- Macrophage adhesion
- Encapsulation
- Capsular contracture
- What regulates protein-material interactions and adsorption:
- Properties of the protein:
- Size
- Charge
- Hydrophobicity
- Stability
- Properties of the material:
- Surface hydrophobicity
- Surface charge
- Topology
- Composition
- Heterogeneity
- Potential
- Properties of the protein:
- Vroman effect: order of protein binding
- Small, abundant molecules bind first, such as Albumin
Coagulation
- Thrombosis: blood coagulation
- 4 steps to coagulation:
- Injury
- Activation of platelets
- Formation of platelet plug
- Blood coagulation
- Intrinsic and extrinsic pathways → common pathway (fibrin polymer network)
- Calcium dependence for both pathways
- How to design material to regulate coagulation: capture calcium, decrease protein binding
- 4 steps to coagulation:
Innate Immune System
- 4 main defense components:
- Anatomic barriers
- Physiological barriers
- Phagocytic cells
- Acute inflammation
- Common cells involved in inflammation:
- Granulocytes
- Monocytes
- Macrophages
- Megakaryocytes
- Order of cell activation:
- Neutrophils
- Macrophages
- Foreign body giant cells (FBGCs)
Wound Healing
- Granulation: formation of many new blood vessels, making tissue look granular
- Neovascularization: formation of new vasculature (blood vessels, vasculogenesis, angiogenesis)
- Fibroblasts: responsible for synthesis of ECM (collagen)
- Foreign Body reaction:
- Continuation of granulation process, attempting to phagocytose the biomaterial
- Monocytes/macrophages fuse into a big multinuclear cell called Foreign Body Giant Cells (FBGCs)
- Fibrous encapsulation: final stage of healing, considered acceptable for biomaterial implants
Case Study on Breast Implants
- Different surface textures (smooth and textured) and can quantify these through SEM and profilometry
- After some time, a fibrous encapsulation forms around the implant
ECM and Mechanotransduction
- Extracellular Matrix (ECM):
- A large network of proteins and other molecules that surround, support, and give structure to cells and tissues in the body
- Transport is regulated by ECM
- Cell + ECM = Tissue
- Emergent behavior: collective property of individual components, commonly used to describe both material and biological properties
- ECM enables emergent behavior from a single cell to an organized structure with functionality
- Primary components of the ECM:
- Fiber-forming elements: collagen
- Link forming elements: proteoglycans, hyaluronan, glycoproteins
- Space-filling elements: same as above
- Free and sequestered factors: growth factors, ions
- Functions of ECM:
- Cell adhesion
- Cell-cell communication
- Cell-matrix communication
- Differentiation
- Why do we care about ECM and biomaterials?:
- Overall design new biomaterial to include aspects of ECM to direct the tissue response
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Description
Learn about biomaterials, their definitions, and examples. Understand how they are classified into metals, ceramics, and polymers. This quiz covers the basics of biomaterials and their applications.
