Learn: BME 300 Exam 1 Learning Objectives & Concepts

Biomaterial (Current Definition)

A material used in a device or system, intended to interact with biological systems.

Biocompatibility

The ability of a material to perform with an appropriate host response in a specific application.

Three major classes of matierals

Metals, ceramics, and polymers

Biomaterials Design considerations

Method or site of application

Forces of load or contact

Biocompatibility

Causes or effects of failure

Biomaterial Requirements

compatible with cells, pose no risk of injury or toxicity, and not be rejected by the immune system.

Bio-inert

Interfaces but does not interact; replaces function; remains stable (silicone implants, false teeth, etc)

Bio-active

Releases factors into the environment; performs a function; may be cleared (bioactive glass and ceramics, vascular stents)

Regenerative

Interacts with and instructs cells; restores tissue anew; replaced by the body (Inductive scaffolds, materials for cell delivery)

Rationale and Design of Biomaterial

Synthetic bone

Design: a 3D-printable ink that produces a synthetic bone implant for bone regeneration and growth

The material is composed of 90% hydroxyapatite (hard and brittle) combined with a biocompatible, biodegradable, elastic polymer.

Rationale: pediatric patients need implants they can grow with, which minimizes repeated painful surgeries.

Four main types of tissues

The original biomaterial is tissue

connective, epithelial, nervous, and muscle

Key tissues properties

ECM, tissue patterning, vascular perfusion, interstitial space, and mechanical properties.

Extracellular Matrix (ECM)

a hydrated network of fibrous proteins and polysaccharides. Most tissues are primarily collagen I fibers. Polysaccharides retain water and cytokines

Adhesive ECM proteins (4)

elastin (stretch), collagens (most abundant, fibrous), laminin (adhesion and crosslinking), and fibronectin (matrix-bound, adhesion).

Summary of microenvironment

many cell types, ECM, chemical and electrical cues, mechanical cues, vascular flow, and interstitial flow

Dynamic reciprocity

ECM composition affects cell function, and cell function affects ECM composition. Cells make enzymes that break down the ECM, so there is constant turnover (remodeling). A "diseased" ECM can cause cell dysfunction.

Structure-function relationship

structure is adapted to function, and changing structure may alter function.

Tissue patterning is shaped by:

Neighboring cells, matrix, and diffusible cues (cytokines)

Environmental conditions (forces, temperature, ions)

Availability of oxygen and nutrients

Vascular perfusion

the diffusion limit of oxygen is about 100-200 µm, so thick tissues need convective perfusion. Achieving perfusion is a limiting factor in artificial tissues.

Interstitial flow

an order of magnitude slower than vessel flow, in 3D, and delivers nutrients to cells beyond the vessel.

Tissue mechanics:

Young's modulus is the slope of the linear region of the stress-strain curve (larger slope means stiffer).

Tissues vary widely. Cortical bone is about 17,000-24,000 MPa, tendon about 560 MPa, skin about 30 MPa, and spinal cord about 2 MPa.

There are three loading types: tensile, compressive, and shear.

Native tissue properties

Provide a design target or benchmark to improve on, replacing ECM functions (ie signals needed to direct complex cell behavior)

Cells must

Attach to a solid surface, which effects their survival, shape, and migration

Mechanosensing/mechanotransduction

ECM transmits mechanical load to cells. cells feel stiffness and shear through integrin receptors (CD44 HA, syndecan)

Effect of stiffness on cells

Affects adhesion, spreading, migration

Migrate towards stiffness (mechanotaxis)

Altes cell behavior and stem cells, cytoskeleton, adhesion, nucleus, gene expression

Primary types of material tests

Mechanical and usage: tension, compression, shear, fatigue and wear (biotribiology),

Chemical analysis: chemical structure and composition

Biomedical tests: cytocompatibility

Tensile test

uniaxial stretch of a molded "dogbone" sample. It characterizes elasticity and strength, and the curve shows brittle versus plastic behavior.

From stress-strain you get Young's modulus (slope of the linear region), yield strength, and toughness (area under the whole curve until breakage).

Compressive test

uniaxial compression to determine load resistance. Shape and thickness must be consistent. It is more common than tensile testing for very soft materials. The calculation is the same as for tensile.

Shear rheology test

measures resistance to opposing forces. It gives storage modulus G′ (elastic) and loss modulus G″ (viscous). It can be linear or rotational.

Hardness test

measures resistance to indentation (F/A). It is fast, easy, and relatively nondestructive.

Tribology

surfaces in relative motion

Fatigue test

stress versus cycle number, with maximum stress often taken at 10⁶ cycles.

Abrasion and wear test

cycles of rubbing. Standardized wear testing is a minimum for FDA device approval.

Cytocompatibility (cytotoxicity) test

put cells with or on the material and count survivors. It can test for killing of specific cells such as bacteria or cancer cells.

Compositional analysis

spectroscopy (species produced when matter interacts with or emits radiation) and spectrometry (often mass). It validates composition before and after implantation.

Viscoelasticity

time- or rate-dependent behavior. Bone loaded quickly fails at a lower point than bone loaded slowly

Caveats to physiological testing

tissues may need to be removed to test, which introduces confounding factors. Test parameters should mimic the biological environment.

Caveats to physical testing

results vary with sample shape and thickness consistency and with loading rate (viscoelasticity)

Caveats to technical testing

results vary by method, and the relative importance of each test differs by application. Each test has limitations, so other measures are needed to compensate.

Stainless steel (Comp, adv, dis)

60-69% Fe, 17-20% Cr, 12-14% Ni, 2-3% Mo

High yield strength, easy manufacturing, availability

Can corrode, high stiffness, low fatigue strength

Cobalt-based (Comp, adv, dis)

30-70% Co, 19-30% Cr, 2-37% Ni, 0-16% W or Mo

High yield strength, high wear resistance

High stiffness

Titanium-based (Comp, adv, dis)

>99% Ti, or Al-V / Al-Nb alloys

Nonallergenic, corrosion resistant

Low wear resistance

Ceramics

inorganic, non-metallic compounds such as oxides, nitrides, carbides, and zirconia. Bioglass, dental screws

Natural Ceramics

Bone and teeth are natural ceramics (hydroxyapatite). Bone is collagen mineralized by calcium-phosphate salt

Metals Advantages

high tensile, yield, and fatigue strength. Shape and properties are controllable by processing. They are bioinert (low reactivity) and radio-opaque for tracking.

Metal Disadvantages

potential metal allergy, stiffness, corrosion, and wear debris.

Ceramics advantages

tough under compression with a relatively low modulus, good wear resistance, can be polished ultra-smooth, can be bioactive, and are somewhat biodegradable. They can be made as liquids, powders, particles, and scaffolds.

Ceramics disadvantages

brittle, low toughness in tension, and low resorption rates.

Grain structure in metals and ceramics

metals are crystalline. Dislocations move easily within grains, but grain boundaries block them. Smaller grains mean more boundaries and higher strength. Ceramics also strengthen with smaller grains.

Ceramic bonding + failure

mostly ionic bonds give high hardness but brittleness. Fatigue cracking is the biggest cause of ceramic failure.

Bjork-Shiley heart valve

A Cr-Co disk was attached to a metal flange with two welds.

The outlet struts failed at the welds by fatigue under cyclic stress.

Closing force was about 10× the opening force.

Young adults exercise more, so they accumulated more cycles and failed at higher rates.

ASR XL hip (metal-on-metal)

It had no plastic liner, so a larger femoral head fit directly into the cup.

Constant wear released metal debris, discovered via blood ion concentrations.

Cells phagocytose the debris, leading to metallosis (metal build-up in soft tissue), inflammation, and aseptic loosening.

Stress shielding

an implant stem that is too stiff transfers less force to bone. Without normal loading, the bone degenerates, which also causes aseptic loosening.

Benefit of Corrosion

passivation: rapid corrosion forms a thin protective oxide layer in the presence of O₂. For example, chromium in stainless steel forms a chromium oxide layer. Passive films can be damaged in the body (low O₂), negating the effect.

Drawback of corrosion

the body is hydrated, so some metals "rust". Corrosion gradually destroys metal by (electro)chemical reaction, and inflammation increases it.

Topography of body

surface features (grinding, brushing, sand or metal blasting) increase surface area and cell-material interaction.

Osseointegration

macrostructures give initial stability, and bone then grows into and around the implant. It takes a while and is not a complete bond. Attachment is enough to break bone on removal.

Osseointegration in hip implants

coating the acetabular surface with metal fibers increases roughness, integration, and pore space.

Biointegration (bioactive ceramics)

a chemical bond forms between bone and ceramic. It is faster and more complete than osseointegration. Bioglass similar to bone

Interactions with bone

osteoconductive (scaffold for new bone), osteoinductive (induces stem cells to become bone cells), and osteogenic (directs stem cells to lay new bone).

Polymers (Definition)

Polymers are subunit monomers linked together. Monomers can be identical or different.

They form by breaking unstable double or triple bonds (e.g., ethylene to polyethylene).

Why polymers are useful

Polymers offer control over properties and processing, and they are naturally more porous, for drug loading

Synthetic vs. Natural Polymers

Synthetic: fully derived using chemical reactions. They are more reliable as raw materials, with more control and less immunogenicity.

Natural: fully derived from natural sources.

Synthetic Polymer Processing types

films (coatings, membranes) or solid parts, fibers, and foams.

Thermoplastics

soften with heat

tangled polymer chains

No cross links, Weak forces of attraction

Thermosets

polymer chains held by strong covalent cross link bonding

Remains hard when heated

Chain chemistry in polymers

Backbone, side groups, pendant groups influence properties

Polymer Morphology (Crystalline, Amorphous, Irregular)

Crystalline polymers are strong, rigid, and less affected by solvents.

Amorphous polymers are softer and more solvent-accessible.

Branches or irregular side groups prevent packing, giving amorphous polymers.

Molecular weight (MW)

An average of the weight, often showing uniform weight (low is most uniform) = long chains = more entanglement

Polymer branching

long branches increase entanglement and strength. Very short branches hinder interaction.

Branching in low density PE

higher strength, lower modulus than linear high-density PE

Failure in polymer

fracture (propagation from an existing defect) and creep (slow, permanent deformation under persistent stress).

Copolymer

two or more monomers (blocks A and B). Properties are a blend.

Crosslinking in polymers

goes from minimal interactions to chain entanglement, covalent connections, and complete connections. Crosslinks can be chemical or physical.

Interpenetrating networks

two entangled networks with blended properties.

Summary of tunable factors

MW and structure, side groups (charge, steric effects), hydrophobicity, crystallinity, crosslinker size, flexibility, and density, and copolymer type and ratio.

Why we build composites

A single-component material may not be strong enough, and transition zones may be needed to mimic biology.

Composite (Defintion)

A composite has two or more constituents separated by a distinct interface: a discontinuous (filler) phase in a continuous (matrix) phase.

Filler in Composite

Stronger and harder, improving stiffness, strength, or toughness, improving bioactivity. Poor interfacing negates benefits

Composite interface mimicry

tendon-to-bone transitions are composites in which fibers from both sides embed in a middle polymer matrix.

Types of composites

Fibrous (long or short fibers), particulate (particles), and laminates (stacked sheets).

Benefit of anisotropy

Fiber orientation influences the stress response. Controlling fiber direction recreates the structure and mechanics of soft tissues such as tendons.

Fiber forming requirements for polymers (4 steps)

Medium to high MW (about 20-250 kDa) for some, but not too much, entanglement.

A linear structure, because branching prevents chain sliding.

Low intermolecular bonding, which prevents chain sliding.

Ordered or crystalline structure, which improves fiber integrity.

Fibers are stronger because the polymer chains align. Bulky side chains may inhibit fiber formation.

Strain-induced crystallization

drawing promotes crystallinity, but low-MW or amorphous polymers may break.

Melt spinning

he resin is melted and extruded. It suits temperature-stable thermoplastics. The extrusion openings dictate shape and number. 10-500 um length fibers.

Wet/gel spinning

for polymers that degrade at high temperature. The polymer is dissolved and extruded into a non-solvent (coagulation). Fibers are grooved from solvent evaporation. Melt and wet spinning give 10-500 µm fibers.

Electrospinning

high voltage on a polymer solution or melt gives smaller fibers (>100 nm).

Bicomponent spinning

two or more polymers are spun simultaneously, giving small dimensions and unique structures. One component can be degradable.

Medical textiles

They are made by weaving, knitting, or braiding. They are strong, flexible, porous, and have excellent fatigue properties and high surface area.

Wovens

strong and dimensionally stable, but stiffer and harder to handle.

Knits

high permeability, flexibility, and suturability, but may dilate after implantation.

Braids

high longitudinal tensile strength, but can be unstable under torsion.

Coronary artery bypass (CABG)

It redirects blood flow around arteries clogged by atherosclerosis.

Risk factors include high cholesterol, obesity, smoking, and hypertension.

Biopolymers types and named poly...

Proteins + Polysaccharides

polypeptides (proteins), polysaccharides (sugars), and polynucleotides (DNA/RNA).

Types of proteins for biopolymers

collagen, gelatin, elastin, fibrinogen/fibrin, silk fibroin

Types of polysaccharides for biopolymers

hyaluronic acid, alginate, chitin/chitosan, agarose, cellulose

Natural polymers are...

free-floating, so most need crosslinking to become solids. Chitin/chitosan and methylcellulose are exceptions.

Chemical crosslinking

covalent, mostly permanent, reliably stable.

Physical crosslinking

hydrogen bonding, semi-reversible, limited stability

Ionic crosslinking

noncovalent, reversible, stable under proper conditions.

Specific chemical types (Amide, photo-crosslinks, disulfide)

Amide (peptide) bonds: strong, irreversible

Photo-crosslinks: light-induced, usually irreversible

Disulfide (thiol) bonds: reversible by oxidation