BMED420 Midterm1

Titanium allows

- Best corrosion resistance and biocompatibility, light-weight, less stress shielding (lower Young's modulus), good bone bonding (best for permanent implants), but poor bending ductility (not good for spinal fixation) and poor wear resistance (articulation against polymers, etc) - Applications: Permanent devices (i.e. hip implants, pacemaker cases, dental implants, screws and nails, craniofacial implants) - Common alloying element: Aluminum (i.e. Ti-6Al-4V)

Stainless Steel

- Biocompatible and low-cost but poor corrosion resistance - Applications: temporary devices (fracture plates, screws, nails) and some permanent implants (i.e. THR with high-nitrogen steels) - Most common: 316L - Methods to enhance corrosion resistance for implant-grade steels: • Add alloying elements: chromium, nickel, molybdenum, manganese • Use metallurgical processing, i.e. vacuum melting (316 à 316L)

CoCr Cobalt-chromium alloys

- Superior to stainless steel in corrosion resistance and fatigue resistance, but expensive and can be toxic/allergenic, and more stress-shielding (due to high Young's modulus) - Applications: Load-bearings implants (hip stems, heads, and cups, and total knee and ankle prostheses) - Other alloying elements with cobalt: Mo, Ni (corrosion resistance), Tungsten (strength) • Ex: CoCrMo stems and heads in total hip replacements

4 Ways a biomaterial can interact with you

-Hurt you -Dissolve _be surrounded by a protective layer -Bond/integrate with tissue

What can we modify on surfaces?

-enhance biocompatibility (often altering protein adsorption) -increase hardness (decrease wear particles) -enhance corrosion resistance -change other surface properties like hydrophobicity/hydrophilicity

Bio-active ceramics

-implant bonds with tissue -ex: hydroxyapatite(Ha) and calcium phosphate (resemble bone) -applications: bone fillers, cements and pastes, coatings for metallic implants, bone tissue engineering scaffolds -excellent biocompatibility -supports osseo(integration (bone)

Bio-degradable ceramics

-material dissolves and it replaced by tissue -ex: HA and Ca phosphate -main application: bone tissue engineering

Main Types of Surface Modifications

-surface coating -surface patterning -surface roughening -plasma modification

Bio-Inert Ceramics

-tissue attempts to reject implant by surrounding with protective fibrous layer (no harm to tissue) -Ex; alumina and zirconia -applications: hip head and cup, other joint replacements, dental implants -ceramics should only be used for compressive loading due to brittleness and sensitivity to stress concentrations

Foreign Body Response

1. Protein adsorption- proteins attach to implant 2. Proteins call neutrophil to try to break down(6-12 hours) and macrophages (2days) 3. Macrophages create huge giant cell and try to breakdown 4. Fibroblasts (3-5 days) try to create layer of dense fibrous tissue to encapsulate implant

What is a biomaterial?

A material used for applications to support, enhance or replace damaged tissue or a biological function -in close contact with living tissue -can be natural or man made -can be therapeutic of diagnostic

Acute Inflammation

Acute (first week-ish): immediate and early response, characterized by fluids and plasma exuding into tissue, and accumulation of neutrophils

Bone is a ______

Ceramic and polymer

Composites as biomaterials

Common for biomaterials: Bioglass-ceramic, allografts, xenografts • Pros: Combines beneficial properties of materials, can be both strong and light-weight, resistant to corrosion • Cons: High cost, often difficult to change shape

Metals as biomaterials

Common metals for biomaterials: Titanium, stainless steel, cobaltchromium, nitinol, gold (most other metals are NOT biocompatible) • Pros: Strong, resistant to fatigue, ductile, can be sterilized easily • Cons: Subject to stress shielding, corrosion, and wear

Corrosion fatigue

Corrosion fatigue is due to concurrent cyclic stress and corrosion (corrosion acidifies surrounding tissues and is corrosive to implant) -"Stress corrosion cracking" describes development of branched brittle cracks >crack growth and failure

What type of bonds typically hold polymers together?

Crosslinks

True or False: A fibrous capsule does not last longer than 2-3 weeks.

False

True or False: All polymers are man-made (synthetically created).

False

True or False: Neutrophils arrive at the biomaterial around 24 hours post-implant and remain for 1-2 weeks.

False

True or False: Thromboembolism will typically occur within the first few minutes following implantation.

False

Fretting fatigue

Fretting fatigue is due to concurrent cycle stress and friction between components or against bone (normal and shear superimposed)

Rockwell hardness

Measures depth of penetration of diamond indenter

Applications of Biomaterials

Medical implants • Methods to promote healing (sutures, staples, etc.) • Regenerated human tissues (tissue engineering) • Biosensors (glucose monitoring devices, etc.) • Drug-delivery systems

Which classification of materials has highly mobile electrons, making for good conductors of electricity?

Metals

3 Main type of Materials

Metals, ceramics, and polymers

True or False: Due to their degradation capabilities, polymeric biomaterials may be desirable for drug-delivery and tissue engineering applications.

True

True or False: Granulation tissue may begin forming 3-5 days after implantation.

True

True or False: Metals tend to be ductile and strong

True

True or False: Polymers are easy to manufacture

True

True or False: The most immediate event following implantation of a biomaterial is protein adsorption.

True

True or False:Acute inflammation can spiral into a long-term, pathologic systemic response.

True

Wolff's Law

bone will remodel based on the loads placed upon it

Stress Shielding

if your device is TOO stiff/strong, the surrounding bone will carry less load and get weaker/less dense!

Collagen is a natural _______ (metal, polymer, or ceramic)

polymer

Encapsulation

• "Foreign body reaction" refers to rejection of the implant leading to encapsulation (composed of granulation tissue and foreign-body giant cells) • It is an attempt to protect body, but may affect implant function • Can coat or modify device surfaces to make this effect temporary (lead to restored normal tissue structure) - Bio-inert - only a thin layer of collagenous tissue

Hypersensitivity

• Also known as "intolerance" • Typically discussed in relation to metals • Undesirable reactions produced by normal immune system, including allergies and autoimmunity

Smart Polymers

• Also known as "stimuli-responsive polymers" or "intelligent materials" • Change according to environment - Example stimuli: temp, humidity, pH, light, etc. - Example responses: altered color, becoming conductive, changing shape, etc.

Controlling protein adsorption

• As soon as you implant a material, it's immediately coated with proteins (within seconds) • The cells attach to the proteins and are interacting with the protein, not the material • Control over protein adsorption gives you control over cellular processes • Without controlling protein adsorption, the result is the haphazard adsorption of proteins that mark the biomaterial as a foreign body > FBR

Infection

• Bacteria can attach to the surface - Can be introduced through surgery • May prevent tissue integration • Can affect device function • Can lead to systemic infection if it spreads in the blood stream • Engineers can add anti-microbial coatings

Bio-active materials

• Bio-active materials physically bond with living tissue - Natural or biomimetic materials are best - Bio-active surface modifications are used to promote rapid and direct attachment of desired cell types to material surface that promote things like osteo-conduction - Main examples: Calcium phosphate, hydroxyapatite (ceramics)

Bio-inert materials

• Bio-inert materials have minimal chemical interaction with surrounding tissue - Non-toxic - Body typically surrounds it in fibrous capsule which can prevent proper fixation, leading to loosening of implants over time - Bio-inert surface modifications are used to block protein adsorption - Key examples: Titanium (metal), Aluminum Oxide (ceramic)

Thrombosis

• Blood-material interaction can trigger coagulation pathways > blood clots (thrombosis) on device • "Coagulation cascade" - see video • Why would coagulation be bad (what are the implications)?

Polymers

• Broad class of compounds based on nonmetallic elements (i.e. Carbon, Hydrogen, Nitrogen), both natural and synthetic, and mostly organic • Typically composed of intertwining long chains of large molecules with a Carbon backbone (covalent bonds) -Characteristics: low conductivity (of heat and electricity), ductile (usually soft and compliant, but can also be rigid -> hard plastics), low strength/mechanical properties, good corrosion resistance -Used for catherters, contacts, IUDs, suture, breast implants

Chronic Inflammation

• Chronic: longer-term response involving macrophages, either leading to: - Repair (fibrosis and new blood vessel formation) OR - Foreign body response/encapsulation/scarring (if foreign material is not removable)

Ceramics as biomaterials

• Common for biomaterials: Alumina, zirconia, and pyrolytic carbon • Pros: Strong, chemically inert, high compressive strength (good for bone implants), can be biodegradable • Cons: Hard to manufacture, brittle à fracture, can loosen and become dislodged, subject to stress shielding • 3 generations: bio-inert, bio-active, bio-degradable

Polymers as biomaterials

• Common for biomaterials: Polyurethane, PMMA, hydrogels, nylon, silicone • Pros: Easy to manufacture and modify, can be bendable for certain applications, can be biodegradable • Cons: Poor strength, can wear and tear • Can be bio-inert, bio-erodible, biodegradable

Composite biomaterials

• Composed of multiple materials • "Best of both worlds" • Usually synthetic, but some natural composites exist, including: - wood (cellulose + lignin polymers) - bone (polymer: collagen + ceramic: calcium phosphate hydroxyapatite)

Metals

• Composed of one or more metallic elements (Iron, Zinc, etc.) and small amounts of nonmetallic elements (Carbon, Nitrogen, etc.) • Metallic bonds (sharing of many free-floating electrons between positive ions) • Atoms arranged in an orderly structure -used for braces, knee/hip replacement, stents etc. -Characteristics: good conductors of heat and electricity, ductile, strong, tough, prone to corrosion

Toxicity is directly related to corrosion

• Corrosion = destruction of metal by electrochemical reaction with environment > release of fine metallic ions • Titanium has good corrosion resistance because of its stable, protective, strongly adherent oxide film

Magnesium alloys

• Degradable • Main applications: tissue engineering, resorbable screws - Can be replaced by regenerating tissues • Safety concerns (metal-related toxicity)

Metals in dental applications

• Fillings, crowns, bridges, tooth root replacements - Often use Co- and Ti-based metals • Orthodontics (braces, retainers) - Often use Nitinol

Hydrophobic coatings

• High contact angle • Want to shed as much water as possible • Bind to proteins more firmly than hydrophilic surfaces

Hydrophilic surfaces

• Hydrophilic surface: "water-loving"...surface will interact readily with water -determine how materials interacts with body

Hydrophobic surfaces

• Hydrophobic surface: "water-fearing"...surface will not interact well with water -determine how materials interacts with body

Tumorigenesis

• Implanted material can elicit excessive and uncontrolled cell proliferation due to particulates or excessive Foreign Body Response (scar tissue formation) • Can be benign/local or malignant, can invade neighboring tissues or invade bloodstream and become systemic

Ceramics

• Inorganic compound of metallic elements and nonmetallic elements • Covalent bonds (shared electrons) or ionic bonds (transferred electrons) -Characteristics: insulators (of heat and electricity), thermally stable (good for high temperature applications), brittle, rigid and hard (resistant to wear and friction), resistant to corrosion -Used for: dentures, heart valve, bone graft, head of hip replacement, x ray tubes

Thromboembolism

• Local blood clot breaks off and travels through circulation to block another important artery/vein • Biggest risk: VTE (venous thromboembolism) > Deep Vein Thrombosis > Pulmonary Embolism (lodged in the lung)

Hydrophilic coatings

• Low contact angle • Instead of forming beads, liquid evenly spreads across surface

Hydrophilic coatings as biomaterials

• Lubricity reduces force required to manipulate intravascular medical devices during interventional procedures - Can decrease frictional force 10-100 fold; reduce risk of damage to blood vessel walls - Ex: catheters, guide wires • Reduce thrombogenicity (blood clotting) • Improved acceptance/bioactivity (stronger tissue adhesion)

Inflammation

• Part of your natural immune response! - Complex reaction of tissue to local injury - Body tries to contain or neutralize the injurious agent or process, and heal the implant site • Intensity/duration of inflammation varies based on size/shape/properties of material à biocompatibility • Clinical features: Redness, swelling, heat, pain • Can be acute or chronic

Toxicity

• Release of wear/corrosion particles > systemic effects • Release of Ni and Cr alloys can lead to muscle pain, decline in cognitive function, memory difficulties, etc. • Additives (i.e. silica powder added to polymer) can be irritants and induce systemic immune reaction • Chemical substances in implants can be carcinogens (ex: Cr and Ni) • Need to minimize corrosion!!

Smart Polymers

• Respond to stimuli ("stimuli-responsive")

Local Response

• Response at the site of the implant/device • Can be caused by the material itself OR trauma or surgery • Types of local responses: - Inflammation - Fibrous encapsulation - Thrombosis - Infection - Tumorigenesis

Systemic response

• Response throughout the body • Types of systemic responses: - Toxicity - Hypersensitivity - Thromboembolism

Hydrophobic coatings as biomaterials

• Self—cleaning ("anti-fouling") - Repel fluids - Ex: surgical tools, urine cups, diagnostic devices (droplets required), drug delivery • Reduce risk of infection in patients • Can be "super-hydrophobic"

Shape-memory alloy

• Shape-memory property of Nitinol (NiTi) is useful for selfexpandable stents, clamps, and clips • Mixed studies on biocompatibility, concerns over long-term systemic toxicity due to Nickel ion release • Expands to original shape in body temperature

Why modify surfaces?

• Surface features have the most direct and major impact on the biocompatibility of a material. We want to make the material more bio-inert, or - even better - bio-active! - Why stop at the surface? Why not make the whole thing out of the fancy biocompatible material? • Because the bulk material governs mechanical properties, durability, and functionality • We want to maintain bulk properties, but modify the surface (on the nanometer scale!)

The ideal metal for bone repair would have: • The modulus of _______ • The fatigue resistance of ______ • The corrosion resistance of ______ • The biocompatibility of ________ • The manufacturing cost of _______

• The modulus of titanium • The fatigue resistance of cobalt chromium • The corrosion resistance of titanium • The biocompatibility of titanium • The manufacturing cost of stainless steel

Important attributes of a biomaterial

•Biocompatibility = no harm to the host body - Non-toxic - Non-allergenic - Non-thrombogenic - Non-carcinogenic - Non-mutagenic - Non-inflammatory • Appropriate mechanical properties for the job

Wear

•Caused by friction •Can lead to aseptic loosening -Generation of tiny particles around device -Particles attract macrophages that engulf particles as foreign bodies (FBR) -Dying macrophages break down and release enzymes and metabolites that are acidic and erode implant and bone •There are also concerns over toxicity of metal wear particles and ions

How can we design for success?

•Choose materials with appropriate mechanical properties for the intended use -Mechanical properties for a stent should be much different than that for a hip implant -Conduct mechanical testing of device under simulated anatomical load conditions •Choose materials with properties closest to native material properties to avoid stress shielding

Hip prosthesis fatigue testing -ISO 7206

•Lower portion of hip stem is embedded in a solid medium in ISO 7206 fixture •Cyclic load is applied to the head of the specimen using test machine, producing bending and torsion, until the specimen breaks or until the chosen number of cycles is attained.

Brinell hardness

•Measures diameter of penetration of indenter

Hardness

•Measures local deformation to an indenter -"Hard" materials are resistant to wear and friction •Most popular tests are Brinell and Rockwell (next slides) •Hardness is roughly proportionate to tensile strength, so you can estimate tensile strength without a tensile test

Fatigue

•Most biomaterials will need to withstand repetitive loading in the body •Fatigue testing involves applying cyclic loading (many cycles) to determine fatigue life and crack growth data, identify critical location, and demonstrate safety -Fatigue fracture is the main cause of premature failure in biomedical implants! -Under cyclic loading, a material can fracture far below its UTS, and even below the yield strength

Fatigue fails

•Tend to be associated with tensilevs. compressive loads •Damage is irreversible •Influenced by temperature, surface finish, presence of oxidizing chemicals, etc.

Wear resistance

•Wear resistance is closely controlled by hardness -Can improve with surface modification like zirconia coating.

Important mechanical properties

•Young's modulus (E) •Ultimate tensile strength (UTS) •Fracture toughness •Elongation at break •Ultimate compressive strength (UCS) -fatigue strength -hardness