Biokompatible Werkstoffe

• any natural / synthetic substance (or combi)

• employed to treat / replace tissues, organs or their function

• capable of being in contact with body fluids & tissues for prolonged periods of time, eliciting little / no adverse reaction

Jede natürliche oder synthetische Substanz (oder Kombination), die verwendet wird, um Gewebe, Organe oder deren Funktion zu behandeln oder zu ersetzen

• ability of material to perform with appropriate host response when applied within specific content in body

1) strong physical bonds

• high yield stress = allows atoms to slide = e dissipate energy (the higher the stress, the more energy dissipated)

2) heterogeneity = high deformatrion volume

• crystalline interfaces, fibers/particles where cracks get stuck, nucelation sites

3) strain hardening

• high flow stress = high elongation = longer deformation in volume = no fractures

4) internal crystal structure

• movement of atom layer = relativ to each other

• amount of volume change of material by stress of deformation

  “how material absorbs & dissipates energy”

1) Covalent

• 2 atoms share 1 / more pairs of electrons

• between non metal atoms (similar electronegativities)

• H2O

2) Ionic

• electrostatic interaction between oppositely charged ions

• NaCl

3) metallic

• free electrons in electron cloud are shared

• Fe, Cu

4) Hydrogen

1. Crystalline:

   • regelmäßige, sich wiederholende Anordnung Moleküle

   • Diamant, NaCl

2. Semicrystalline:

   • Kristalliner + amorpher Bereich

   • PP, PE, Nylon

3. Polycrystalline:

   • keine langfristige Anordnung, jedes Korn hat eigene Kristallstruktur

   • Metalle, Keramik

4. Amorphous:

   • keine geordnete Kristallstruktur

   • Glas, Polystyrol

• non-metallic, inorganic

• composed of metallic & non metallic elements via covalent & ion bonds

• made by heating raw materials (like clay) to high temperatures

• hard and brittle

• polycrystalline

Vorteile:

• High Hardness and Strength

• high melting point

• good electric insulation

• biocompatability

• Resistant against: corrosion, microbial attack, temperature, pH changes

Nachteile:

• Brittleness (no plastic flow)

• difficult to deform plastically wegen bonding type

• limited ductility

small changes in composition = affects whether they are: bioinert, resorbable, bioactive

fabricated by: synthetizing powerds, followed by shaping & consolidation process

= used to repair / replace skeletal hard connective tissue

• Inorganic glass: eyeware, chemical ware

• Insoluble porous glass: carriers for enymes

• Aluminium Oxide (Al2O3): facial surgery

• ZrO2: dental restauration & implants

• Hydroxylapatite: bone replacement

• Glass ceramic: dental restauration

• Bioactive glass: middle ear & facial surgery

success depends on:

• stable attachment to connective tissue

• stimulating repair & regenaration of bone when used as particulates for bone grafting (Fördert die Reparatur und Regeneration von Knochen, wenn es in Form von Partikeln für Knochentransplantate verwendet wird)

Ceramis:

• Al2O3: as articulation bearing surfaces (Gelenktragflächen)

• Hydroxyapatite / Glass ceramics: coating for metal prothesis

Reason:

• superior wear resistance (vergleich zu metal auf metal / metal polymer) (Verschleißfestigkeit)

• resistance to further oxidation

• high stiffness

• low friction

Realized by:

• full-density. controlled, small & uniform grain size (<5microm)

  -> internal stresses cannot dissipate as in ductile (hohe Dehnbarkeit) materials

• high density & purity

• processed by pressing & sintering at T = 1600-1700

Properties:

• excellent corrosion resistance + wear resistance

• good biocompatability

• high strenght + hardness

• low friction & wear (Reibung & Verschleiß)

used in: load bearing hip protheses & dental implants

strenth, fatigue resistance & fracture toughness (of polycrystalline alumina) depend on porosity & grain size

• ingrowth of tissue into pores on surface / through implant

  -> decreases interfacial area

  -> increased resistance to movement

  -> interface established by living tissue in pores (biological fixation)

  -> can withstand more complex stress than type 1

Limitation:

• tissue need to remain viable & healthy

• pore diameter 50-150microm (provide blood supply)

• if micro movement = tissue damage = blood suppy cut of = inflammation = interfacial stability detroyed

• component of bone tissue

• plays a crucial role in the mineralization of teeth and bones

Coatings: on metallic implant substrates, by electrophoresis, sol gel routes, biomimetic routes

Properties influenced by:

• coating thickness: influences coating adhesion & fixation = 50-100 microm

• Crystallinity: affects dissolution & biological behavior

• Biodegradation: affected by phase purity, chemical purity, porosity & crystallinity

• Adhesion strength: 5-65 MPa

• Ultrathin bonding zone: very high gradient in elastic modulus at bonding interface between HA & bone

= direct & functional connection between living bone & surface of loadbearing artificial implant

• bioactive material that can bond to bone & stimulate tissue growth

Vorteile:

• Bioactivity

• Biocompatability: safe use in body

• Versatility: DDS at controlled rates -> releasing ions that stimulate bone growth (Vielseitgkeit)

• designed to interact positively with the biological environment

• materials can actively form a bond with surrounding tissues va. bone

  -> bioactive glasses and hydroxyapatite

• materials that can be absorbed and metabolized by the body over time

  -> Calcium Phosphate, Kollagen

Purpose:

• tissue regeneration: rovide temporary support for tissue healing and regeneration while gradually being replaced by natural tissue

• minimize need for removal: zB. durch surgery

• drug delivery: used to deliver therapeutic agents directly

• veneering for metal / ceramic frameworks

• all ceramic restoration

• implants

• bone replacement materials

• restoration

Processing:

• press ceramics

• lamination

• CAD-CAM

• 3D printing

Benefits:

• good corrosion resistance

• very good esthetics

• good biocompatability

• x-ray opacity can be easily adjusted

• electrically non conductive = no galvanic elements

• low thermal conductivity compared to metals

Drawbacks:

• complex processing

• low fracture toughness compared to metals -> sensitive towards defects WEIL no plastic deformation

• stretch concentration at notches = part breaks already at low macroscopic stress level

• Fracture toughness = related to energy dissipation during crack growth

Fracture toughness = resistance against crack growth !

Parameter to obtain high strength:

• small grain size: through nano-scale powders & low sintering T°C

  -> Problem: multiple scattering events, poor translucency, lower solid loading = large shrinkage

• Low porosity: by applying high sintering T°C

• incoporation of crack stoppers: fibers -> more heterogeneity, lithium disilicate glass ceramics

• transformation strenthenig / toughening

Properties:

• high Strength + Hardness

• Biocompatability

• High thermal stability

• Aesthetics

• Corrosion resistane

  
  

dental use:

• crown copings, bridge frameworks, abutments

• processed by CAD/CAM techniques (milling), AMT

• for production: refractory materials, grinding wheels (in combi with aluminoxide), cutting tools (kitchen knifes to high speed cutting in industry)

Green:

• shaping & forming ceramic powders into desired shape before sintering (green before fired)

White:

• steps after initial sintering + treatments to improve properties

= to enhance mechanical properties of zirkonia

3 Phases:

• Monoklin T°C < 1200°C

• Tetragonal T°C: 1200 - 2370 °C

• Cubic T°C > 1200°C

Strenghtening through Phase transformation from tetragonal to monoklin (heterogenous nucleation) UNDER STRESS

-> larger volume = closes cracks

-> increased toughness

-> resistance to crack propagation

Verbesserung der Festigkeit & Zähigkeit basiert auf Phasenveränderung die zu Volumenvergrößerung der Kristallstruktur führt

Bonds

• no directional (anisotropic) bonds due to metallic bond

• caused by electron gas = atoms arrange in a way that saves as much space as possible

Vorteile:

• High strength: high tensile & compressive strength

• Ductility: can be deformed without breaking, extensive shaping & forming processes

• Malleability: can be rolled or hammered into sheets

• Conductivity

• durability

• recyclability

Nachteile:

• corrosion

• weight

• thermal expansion

• cost

• brittleness

1. Solid solution strengthening:

   • andere Atome ins Metallgitte einfügen = schwieriger zu Verformen = Festigkeit

2. Cold working:

   • Metalle bei Raum T°C mechanisch bearbeiten = Veränderung Mikrostruktur = erhöte Festigkeit

3. Grain refinement:

   • Größe Kristallkörner verkleinern = mehr Korngrenzen = Barriere für Bewegung = Festigkeit

4. Precipitation strengthening:

   • Einbringen von Partikeln = blockierte Bewegung = Festigkeit

Requirements:

• Mechanical strength

• Adequate wear behavior

• Corrosion resistance

• Biocompatability

mechanical properties by: type of phase + amount, distribution & orientation of phase

• adpted by: changing composition, alloying, manufacturing

= extent to which material can be plastically deformed without rupture

Characteristics:

• ability to stretch

• plastic deformation

• strain

• influenced by: T°C, crystal structure, grain size, impurities & alloyment

  -> zB: Alu, Kupfer, Gold

• cast: dentistry & artificial joints (molten metal)

• wrought: stems of prothesis for heavily loaded joints (forging, Rolling, extrusion)

Cobalt-Chromium-Molybdenum

-> alloy melted at 1350-1450C°, poured or pressurized into ceramic molds of desired shape

-> femoral stems, oral implant, cardiac stent

Properties:

• high strength

• wear & corrosion resistance

• biocompatability

• durability

schlecht: brittleness

Vorteil:

• biocompatability:

  -> stable TiO2 coating on surface

• high strenght & stiffness

• low weight

Nachteil:

• pure Ti: hexagonal crystal structure = low ductility

• sensitive to oxygen, hydrogen & nitrogen = difficult to process metal (casting, welding)

  
  

Phase transformation:

• diffusion controlled during slow cooling (a->b)

• Screw type implant

  1. Implantation

  2. cover scrw put in & left till implant integrates with bone

  3. cover screw is removed & abutment attached to implant

  4. crown is attached

• healing: 8-12 wochen

• Stents (endovascular prothesis) for arteriosklerosis

• tools for minimal invasive surgery

• wires for orthodontics

• tools for root canal removal

• Importance of surface preparation: Electropolishing ! (dünne Metallschicht wird entfernt)

• biodegradable & bioabsorbable material for medical implants

Vorteil:

• temporary implant application - short term structural support - then reabsorbed

• corrosion products are biocompatible: human body contains 24g Mg in muscle & bone

• high specific strength & elastic modulus ähnlich wie human bone

Nachteil:

• low corrosion resistance = reduction mechanical integerty before bone in comp. healed

• formation of hydrogen: bubbles can accumulate around implant = delay healing, change of pH

• low ductility due to hexagonal crystal structure

Approach: casting followed by extrusion (grain refinement, gf)

• Zn: improves castability, leads to gf, increases strenght

• Ca, Zr: help gf

• Mn: catches material impurities -> better corrosion properties

• Yb: prevents grain growth during soldification, improves corrosion resistance, improves age hardenability (precipation hardening)

• large molecule composed of repeating monomers

• covalent bonds

• synthetic / natural

Requirements:

• biocompatability

• processing with conventional methods

• sufficient mechanical properties

• sterilisability

• long term stability in vivo

• purity (restricted number of additives & residues)

1. addition of monomer to growing chain with reactive terminus (growth only at one end)

2. monomer concentration decreases steadily with increasing reaction time

3. molar mass increases - doestn change further

4. after temination: reaction chains arent active

5. initiator required

1. reaction can occur between any pair of molecular species -> groth thoughout Matrix

2. rapid loss of monomers, in favor of low oligomers

3. living polymer - ends remain active

4. no initiator required

• linea / branched macromolecules

• reversible softening (reheated & reshaped)

• recyclable

• flexible to rigid

  -> zB: Polythylene

• (mostly) loosely crosslinked

• flexible & elastic

• soft & flexible -> no plastic flow at T°C of composition

• resilence: good shock absorption

• wide T°C range: lots of properties

  -> zB: natural rubber, silicone rubber

• irreversible curing: once set, cant be reshaped

• mechanical strength: strong & rigid -> remain hard until T°C on decomposition

• chemical resistance

• high thermal stability

• chemical process resulting in cleavage of covalent bonds

• natural process through microorganisms

• biological agent is causing degradation of implanted device (=enzyme, cell, microorganism)

  
  

• physical change in size, shape, mass of shape

• no specific mechanism involved

• Degradation products removed by cellular activity

• not clearly defined yet

decomposed in body by:

• macrophages, enzymes, hydrolysis

• days - years

quality characterized by:

• narrow molar mass distribution

• minimal impurities

• well defined chemical structure

• low residual monomer contact

Application:

• orthopedics (screws, plates)

• stents

• drug delivery systems

• scaffolds

• suture materials

• Polymer dissolution

• Hydrolysis

• Enzymatic degradation

• Dissociation of Polymer-polymer-complexes

Aim:

• products should be integrated into bodys metabolism

• Molar mass: < 40000 - 50000 g/mol in order to use common processes of excretion / secretion zB: liver, kidney, lung, skin etc.

• cleavage of covalent bonds

• due to thermal / mechanical processes

• destruction of entire polymer backbone

  
  

• in case of: Hydrolytic instable bonds (ester, amide groups)

• Inversion of Polycondensation

• Controlled diffusion by water molecules

• Catalyzed by: T°C, acids, base or enzymes

• at specifi groups identified by enzymes

• Hydrolytic, oxidative or chain scissiom

• high molecular weight enzymes do not diffuse into polymer -> surface degradation

• via solvation of macromolecular components

• until gain of free energy > intermolecular cooporative interaction Energy (between two polymers)

Amalgam -> Composite (aus einer Mischung von Kunststoff (Kunstharz) und feinen Glas- oder Keramikpartikeln)

Enamel:

• 92% Hydroxyapatite

• 6% Water

• 2% org. Matrix

Dentin:

• 70% Hydroxyapatite

• 20% Water

• 10% org. Matrix

• Processability: Viscosity, Reactivity, Shrinkage

• Mechanical properties: Hardness, Strength, Fracture Toughness

• Biocompatability

• Aestethic porperties: Translucency, Color, Opalescence

• Corrosion properties

• Initiatior: thermal, photochemical

• Reactive diluent: forms polymer backbone

• Crosslinker: forms covalent bonds between chain, influences mechanical properties

• Filler: up to 90% - particles, fibers, polymers

• Additives: Color, Rheology

Caus shrinkage during polymerization (or internal stresses) = potential clinical problems (marginal gap)

FOTO !

Gut:

• Leightweight: low density

• Versatility: wide range of properties

• Good insulator

• Flexibility: elastic & flexible

Schlecht:

• Low melting point

medical device to:

• replace missing bio. sturcture

• support a damaged bio. structure

• enhance an existing bio. structure

-man made device

-surface made out of biomaterial (when in contact to body)

-can contain electronics: pacemaker, cochlear implant

-some are bioactive: drug delivery system zB: implantable pills

• any instrument, apparatus, implement, machine

• intended by manufacturer to be used alone / in combi

• for one / many purposes: diagnosis, prevention, control of conception, supporting life

• Europe: CE Mark, EMA

• USA: FDA

Medical Device Directives:

• 93/42/CEE for Medical Devices

• 90/385/CEE for Active Implant Medical Device

• Risk for patient is low

• non invasive / no interaction with body

• 50% of MD commercialised

• no need to be biocompatible

  zB: hospital beds, arm slings, stethoscope

• Risk for patien = medium

• Invasive & prolonged with interaction MD & body

• interacts with one of the orifice of body

  zB: lenses, catheter

• Risk for patient = high

• invasive & permanent contact with body

• Contact with damaged tissue / skin

  zB: Implants, Sutures, Wound dressings

• Non-degradable! -> require biocompatability!

• Risk for patient = high / critical

• invasive or permanent contact with body

  zB: neurological catethers, artificial valves, dermal fillers, drug eluting stent

• requires Biocompatability !

• requires proof of therapeutic effect & no toxicity

= Principles ensuring ethical treatment of animas in scientific research

1. Replacement: use alternative methods (in vitro, computer modelling)

2. Reduction: Minimalize number of animals

3. Refinement: Modify procedures to minimalize pain & suffering

scope of pre-clinical studies:

• characterize biomaterials / implants

• validation of efficacy / expected performance

• includes:

  • chemical / mechanical / physical properties

  • Cyto- & Biocompatability

  • Sterility

  • Stability

• biological response initiated by body when foreign material (implant, med. device) is deteched

• Proteins (from blood & tissue fluids)

  -> adsorb onto surface of biomaterial

  -> stage for bodys immune response

• Immune cells recruited to site of implantation

• attempt to eliminate foreign material

• release of cytokines

• Object persists -> Immunce cell recruit = Macrophages & Lymphozytes

• secrete inflammatory factors

• Macrophages (unable to engulf foreign Material)

• Fusion = Formation of Giant Foreign Body Cells

• Trying to isolate impant by Fibrous capsule

  -> composed of collagen

  -> produced by fibroplasts

• Formation of thick tissue layer around implant

  
  

• Quality & nature of clinical intervention

• wide patient-to-patient variability (age, sex, general health)

• Design of device

• Physical relationship between surface & body

• Presence or absence of microorg. or endotoxins

• Anatomical location

Material & Requirement:

• cleanable

• drying behavior

• accessibilty of entire surface for sterilising agent

Sterilisation method & Requirement:

• material specific

• appropriate packing

• possibility of multiple sterilisation

• formation & release of toxic substances

• relies on: time, pressure, temperature

• can be applied differently:

  • Gravity: most common & basic sterilisation cycle, steam pumped into chamber contaminating air, steam has lower density than air = steam displaces air in chamber by gravity

    -> Glassware, unwrapped goods

  • Pre-vacuum / Post-vacuum: air removed mechanically from chamber & load with a series of vacuum & pressure pulses, steam also penetrates porous areas (couldnt be reached with gravity)

    -> cages, porous material

• dry at T°C > 160°C

• Coagulation of proteins & oxidative damage

• higher T°C & longer exposure time than steam

• high T°C-Resistance of material !

Application:

• No toxic residues (compared to cold steam procedures)

  • usefull for material with high T°C-Resistance

  • not sterilisable by steam zB: hygroscopic powders

Limitation:

• not suitable for towels, paper, fabric -> burnable

• Liquids in sealed container -> burst

• heat transfer = bad in air to solid

• by microbiocidal gas / gas mixture

• for Materials sensitive to heat / radiation (plastics, optics, elctrics)

• MD exposed to reactive gas in HIGH concentration

• load: packed in foils & films permeable for gas

• Validate absence of remaining gases at end

  
  

1. vessel is evacuated

2. steam moisture introduced (>40% humidity)

3. gas (-mixture) injected 600-1200 mg/l

4. T = 40-50°C to achieve required SAL

   • Overpressure: 6% EO & 94% CO2 at 1,7 bar

   • below atmospheric pressure: 100% EO

Properties:

• toxic, carcinogenic, extremly flammable

• strong: microbicidal, virucidal, fungicidal & sporicidal effect

• highly diffuse: penetrates well, migrates though textiles, paper, some plastics

Application:

• surgical sutures

• Intraocular lenses

• Ligament & tendon repair devices

Limitations:

• Handling

• Time of desorption (depends on material)

• colorsless, inflammable, pugent odor, toxic

• effective & easy use

• water vapor + active diffusion by pressure changing -> low T°C steam & formaldehyde sterilization process

• high humidity: 5-15 mg/l formaldehyde

• removal of residues -> steam wash = no need of desorption

• sterilisation T°C: 50-80°C -> limitation for thermal sensitive material

Limitations:

• less diffusive (coef 100x lower than EO) - insufficient penetration

  -> need pressure cycles to achieve active transport

  
  

Penetrating Power:

• E-Radiation: high dose rate, low penetration depth

• y-Radiation: high penetration depth & low dose rate (metallic components are penetrated)

Mechanism: radiation interacts & destoys DNA & cell membrane & deactivates them

• E-Radiation: cathode rays, vacuum, 2 electrodes & high voltage

• y-Radiation: radioactive sources 60Co, 137Cs

• X-Ray: Bremsstrahlung radiation, short exposure time, decrease damage of polymer

Vorteil:

• efficient & easy control

• high penetration depth

• no residues at sterilising agent

• complex geometries possilble

Nachteil:

• physical & chemical changes in material

• polymer chain scission

• high costs

• disinfection of rooms, rinsing warer for disinfection machines, endoscopes water

• highest effectivess = lamda = 254 nm

• UV dose = UV light intensity * exposure time

Nachteil:

• low penetration depth = only surface effective

Plasma = 4. state of matter, created when gas is heated / exposed to strong electromagenetic field -> ionized gas

• T°C: 37-60°C & low pressure

• va. hydrogen peroxide vapors converted in gas plasma

  • generation of free radicals that react with molecules (kill via oxidation)

  • essential in metabolism & reproduction of micro-organisms

• Suitable for:

  • heat & moist sensitive device

  • no toxis residues

  • short aeration time

• Limitations:

  • free radicals can influence molecular structure of polymer

• Retention of micro-organisms on surface

• Matieral: membrane filters made of cellulose derivates / synthetic polymers

• sterilisation of gases & liquids

• Pore diameter: 0,45 - 0,10 microm

Limitation:

• Mycoplasma: deformable -> lack of cell wall

• Spirochaete: diameter: 0.1-0.6 microm & länge: 5-250 microm

• with aqueous solution = disinfection process (not sterilisation)

• microorg. only harmed & can no longer provoke infections

• bacterial spores barely eliminated

• differenttreatments combined = increase of effectiveness!

• 3D network of:

  • convalent bonds

  • physical cross links from entaglements

  • ionic interaction

• Sourece:

  • natural

  • synthetic

• Method:

  • cross link of polymers

  • simulatneous polymerization

• Components:

  • Homopolymer hydrogel:

  • Copolymer hydrogel:

  • Multipolymer hydrogel:

• Ionic charge: neutral, cationic, anionic, ampholytic (+&-)

• Vorteil: bessere mechn. Eigenschaften & self-healing

Medical Application:

• Lubricants: dry surfaces of catheters, drainage tubes, exhibit high friction coefficients (injure surrounding tissue)

• Blood containing hydrogel: nonionic, prepared from polyvinylalcohl, polyethyleneglycol (PEG)

• Contact lenses (soft)

• Wound dressings: flexibility, non-immunogenicity, barrier effect -> hydrogels posses all these exept mechanical strength -> creation of comopsite blends

Pharmaceutical:

• Drug delivery system

• device that enables the introduction of a therapeutic substance into body

  -> controlls rate, time & place of release

• Pharmacodynamic (PD): effect of drug (chem, phys, …) on organism

• Phamacokinetik (PK): determines fate of substance

• LADME (liberation, absorption, distribution, metabolism, excretion)

• active agent contained in reservoir surrounded by polymer membrane

• release by diffusion through rate controlling membrane

Requirements:

• Biocompatability

• Easy application

• Safeness against overdose

• Reproducible & constant release rate

• Transdermal therapeutical system (TTS)

• Cover membrane: rate controlling

• Microporous selective permeable membrane

• Liberation: by diffusion -> constant concentration gradient -> constant rate of release

Safety: rupture of membrane = sudden release of drug !

Osmotic pump

• strong water permeable membrane

• flexible membrane impermeable for water & drug

-> due to body fluid contact: water diffuses through strong membrane (higher concentration of salt in device than body fluid)

FOTO!

Backbones with pendant drug (degradable system)

• Carrier systems: active substance bound chemically to main chain or on backbone

  • main chain bound active agents

  • side chain bound active agents

Requirements for carrier material:

• Biocompatability

• Stability during sterilisation

• (Bio)degradable

• Solubility + easy processing

• Coupling of drugs

• Cell specific reaction

! Compatability shouldt change during exposure !

• treat cataract (lenses become cloudy)

  -> age related proteins aggregation

Optical porperties:

• Optical clarity important for: contact lenses, artificial corneas, IOL

• Optical clarity achieved by:

  • amorphous polymers -> low / zero crystallinity

  • polymers with phase separated domains in 100nm or less size range (these domains will not scatter light)

• prothesis (corrective lens) placed over cornea -> corrects vision

• Hard CL: rigid, durable, low gas permeable

• Soft CL: flexible, faster adaptation to eye, high water content material (hydrogel)

• PMMA: strong intermolecular interaction, durbale, transparent, low gas permeable

• Silicone: hydrophobic, not comfortable to wear, poor wetting

• pHEMA: hydrophilic, better for SCL, 20-80% H2O

• PVA: hydrophylic hydrogel, inexpensive

• non-invasive continous glucose monitors, from tears -> Diabetic population

Sehhilfe + mit Sensoren versetzte die bestimmte Werte direkt aus dem Blut ablesen zB: Blutzuckerspiegel

• device implanted into heart to replace dysfunctional native heart valve = high flex fatigue life, when reinforced with PET fibers = minimal creep deformation

• Mechanical: prone to thrombosis, need anti-coagulant (anti-blutgerinnung)

• Bioprotheses: xenografts / allografts, risk of immune rejection

• Polymeric: poly SIBS rubber

Requirements:

• high creep resistance

• excellent hemocompatability & biostability

• Inertness prevetns degradation

• Nickel 12%, Chromium 17%, Molybdenum 2%, iron asp 100%

• Austenitic stainless steel: specific crystaline sturctue -> possesses austensite as primary strucute = high resistance to corrosion

Limitations:

• elastic deformation limited to 1%

• smooth muscles proliferate (event. closing stented vessel)

• Corrosion triggers release of ions

• lack of Biocompatability!

  -> only: wires / surgical tools

Nitinol:

• hyperelastic

• shape memory + self-expanding stents

• biocompatability - resistance to corrosion

Stress-induced-phase-transformation (diffusionless change)

• Autensite: higher T°C & no / low stress = cubic crystal phase -> strong & stiff

• Martensite: lower T°C & stress = tetragonal / monoklin -> soft & ductile

nach entdeckung: neointimal hyperplasia -> Einsatz von antiproliferative agents (inhibit cell cycle pathways, prevent T-& B-cell proliferation)

Heute: fully degradable polymer stent: metal + polymer

(First generation:

• Drugs: Sirolimus & Paclitaxel

• Composition: stainless steel + polymer coating

• 2006: report of dead cases -> delayed endothelialization & hypersensitive reaction to polymers

Second generation:

• new composition: metal alloys zB: cobalt-chronium

• faster drug release = zotarolismus, everolismus, novolismus

Third generation:

• Polymer-free-coated DES: Pores / rugosity to release drugs, micro-drops by crystalization)

Composition

• Inner part: saline solution / silicone gel

• Outer part: cross-linked silicone rubber, containing amorphous silica (enhance tensile strenght + tear resistance)

  
  

long term aging of silicone rubber:

• degradation of base polymer to lower average molecular weight components

• degradation = production cycling components

• cross linking: embrittles rubber

• degradation of bonding: silicone polymer & silica reinforcing agent

• swelling of silicone shell

Leading to:

• focal rupture with pinhole size holes:

  • large visible tears

  • gel bleeding: escape of silicone

New generation:

• multi layered shells, barrier layer implant: high stability

• rough surfaces: decrease risk of capsular contracute

• cohesive silicone gel implants: eliminate filler leakage

• to give protection & assist in healing

• important to restore skin integrity (maintaining homeostasis!)

• Selection based on: condition, exudate, presence of infection

Requirements:

1. Haemostasis:

   • constriction blood vessels

   • platelets aggregate at wound site -> form clot by releasinf Fibrin

2. Inflammation:

   • white blood cells -> clear debris, bacteria & dead cells

   • Cytokines + growth factors

   • Redness, Swelling, Heat & Pain

3. Proliferation:

   • Fibroplasts produce collagen -> new connective tissue

   • Angiogenesis: Formation new blood vessels

   • Formulation Granulation tissue

4. Remodeling:

   • Collagen wound remodelled -> becoming more organized & crosslinked

   • Apostosis: removing excess cells & blood vessels

   • 80% of original strength

• haemostatic properties: release of calcium ions

• promotes debridement of slouggh

• can absorb 20 times own weight -> for wounds with large amounts of drainage

• moist wound healing

• promotes debridement & formation of healthy granulation tissue

• Waterproof

• for non infected wounds

• low to medium exude wounds

Composition:

• hydrophilic colloidal particles of gelantine, cellulose, pectin chitosan

• low molecular weight polyisobutylene

• highly absorbant (20 times weight)

• non adherent / adherent wound contact layer, hydrocellular foam & waterproof outer layer

• früher: aus marine sponges

• heute: polyurethane or silicone

• high water content 96% -> moisture environment

• good compatability with skin

• made of hydrophilic polysaccharide / PVG, Polythethane

• requires secondary protective dressing!

• help in debridement (Entfernung abgestorbenes Gewebe)

• absorbs high amound of liquid without dissolving

• can be loaded with therapeutics!

Medical:

• biocompatability

• early mobilisation

• simple surgery technique

• adated to bone architecture

Construction:

• simple in: material, function & construction

• easy implantation & reoperation

• adaptaility on different patients

Material:

• wear resistance & low friction sliding surfaces

• sufficient statig & dynamic strength

• stiffness adopted to bones

• high toughness, narrow property tolerances

• transfer of high static & dynamic loads

• in case of:

  • extensive damage of fermoral head & neck segments

  • osteoporosis

• 3 Parts:

  • Stem: fitted into femur = stability

  • Head: replaces head of femur

  • Acetabular cup: fitted in pelvis, replaces surface

• Fixation: cemented, pressed

• Material: Ti, Ti-alloy, CoCrMo-alloy, stainless steel

• Length: 135-185mm (reoperation: 180-230mm)

• Fixing site: proximal (in upper spongy region of femur), distal (lower part)

• Design: Slim lined shape of stem

• Geometry: overall shape, cross section, presence of collar

Surface & coatings:

Ingrowth:

• bone grows inside porous surface

• 50-400nm pore size, 30-40% voids to maintain mechanical strength

• sintered beds: microspheres of CoCr / Ti-alloy by high T°C -> porosity 30-50%

• fiber mesh: porosity 30-50%

• porous metals

Outgrowth:

• bone grows onto roughened surface

• grit blasting: textured surface by bombarding implant with small abrasive particles, surface roughness 3-5mm

• plasma spraying: metal powders mixed with inert gas, pressurized & ionized to form high energy flame

  -> less interconcting than ingrowth

Hydroxyapatite:

• plasma sprayed directly on implant / porous coating

• osteoconductive

• optimal d = 5mm

Modular:

• taper of shaft to position

• standard diameter: 22, 28, 32 mm (increasing size = increasing mobility)

Common used:

• Alumina, Zirconia

• CoCrMo alloys

• Oxinum (Zr + Nb) -> abrasion resistant + lower friction against UHMW-PE

Partial Hip replacement: hip hemiarthroplasty

• surgical procedure -> only femoral head is replaced

Materials:

• Alloys: Ti, CoCrMo, Al2O3

• Coating: Hydroxyapatite, Titanium

Fixation:

• Press-fit

• With bone cement

Polymers:

• articlutating bearing surfaces

• cementing material

UHMW-PW:

• low coefficient of friction & low wear rates

• creep resistance

• yield strenght -> minimalze plastic deformation

• wear debris

! in vivo: failure of ceramic HJI is low

-> Problem: fracture, noises, price

Fracture:

• every ceramic has defects

• slow crack growth -> fatigue

• Stress rise at crack tip

• critical crack grwoth -> explosion

Noises:

• component malpositioning

• prothesis design

• acitivity level & weight

• micro separation

Squeaking = warning !

-> increased friction due: diminished lubrication, wrong cup position, bearing roughness

1.Metal-on-Metal:

• Cup & head made of CoCr-alloys

• Stem made of Ti-alloys

• Problem: wear particles, corrosion, metallosis

2.Ceramic-Polymer:

• Head -> ceramic cup (Al / Zr)

• Cup -> polymer (PE-UHMW)

• low coefficient of friction

3.Ceramic-on-Ceramic:

• Cup & head: Al, Zr, or MIx (Al 75%, Zr 25%)

• Problem: Ceramic implants break, squeezing, total failure

4.Metal / Polymer:

• Ball: metal (stainless steel, Ti, Co/Cr)

• Acetabular cup: metal (CoCr)

• Articulating part: Polymer

5.Ceramic/Metal/Polymer:

• Ceramic head -> Al

• Acetabular cup -> metal

• Articulating part -> ceramic or UHMW-PE

Longevity & performance abhängig von:

• activity level

• weight

• general health

• wear

• attracks water molecules = wettable surface

-> lower protein adsorbtion

-> reuced cell adhesion: weaker inflammatory response

-> often more Biocompatible

• amorphous solid, disordered

• no large crystalline structure

Vorteil:

• transparent

• no thermal expansion

• chemical resistance

Nachteil:

• brittleness (tempered glass = toughened)

• formed as amorphous glass

• controlled crystalization = creates fine crystals = crystalline phase

• Crystalline + amorphous phase

Vorteil:

• high mechanical strength (stronger than ceramic & glass)

• transparency, opacity

• Biocompatability

International Organisation of Standarts

• develop & publish inernational standarts

• increase strength

• reduce shrinkage

• improve wear resistance

• improve asthetics

  
  

1. Polylactic Acid:

   • Hydrolysis = breaking into lactic acid monomers

   • moisture & microorganisms

2. Cellulose based Polymers:

   • broken down by cellulase enzymes from funghi & bacteria

   • product: glucose

• process where polymer forms / cures when exposed to light (visible / UV)

1. Initiation: light activates photo initiator -> generates reactive species

2. Propagation: reactive species attack double bonds -> chain reaction -> formation polymer network

3. Termination: Solid cured polymer

• Flexibility

• Shock absorber

• Transmission of chewing forces

-> helps in design: dental composites & implants

Use:

• total hip replacement

• screws & fixation devices

• cranio facial surgery

• dental implants

• TiO2 coating on surfce

  -> chemically stable

  -> protoective

  -> self healing layer

• Bioinertness: doesnt trigger immune response

• Prevents harmful release of ions

• Promotes osseointegration

• ability of material to support growth of new bone

• serving as guiding scaffold for bone cells to grow:

  • along surface

  • into pores

• Gold alloy: crowns, bridges, inlays = durability, malleability, corrosion resistance

• Ti + alloys: dental implant, abutments = corrosion resistance, biocompatability

• Stainless steel: orthodontic wires

• allotropy (of lattice structure)

• Pure Ti: hexagonal (alpha) up to 882°C & above = cubic body centered (beta)

• Phase trafo: diffusion controlled during cooling (alpha -> beta) = martensitic lattice transformation

• Al, Zn, O: alpha (hdp)

• V, Cr, Fe: beta (bcc)

• Alpha beta alloys = best mechanical propertis ! (Al, V stabilizer)

1. Strong Ionic / covalent bonds: bonds = rigid -> atomic planes cant slide past one another

2. Brittleness: lack of ability to absorb plastic deformation -> fracture under shear stress

1. Amorphous polymer: low / zero crystalinity

2. Polymer with phase separated domains: 100nm or less size range -> do not scatter light

3. Reduce grain boundaries -> minimalize light scattering

affects Polymers: chain scission or cross linking -> bad for mechanical properties

• Bonds: covalent within chains, VDW betweeen

• Low melting point: weak VDW between chains

Overview of:

• Time of Application

• Application method

• Effects to consider

Test:

• Cytotoxicity = cell damage

• Sensitization = allergic reaction

• Systemic Toxicity = impact on entire body

• Carciogenicity = potential to cause cancer

• Protection from contamination, physical damage, light, moisture

• Sterility maintanence

• mechanical Protection

• Information: Batch number, expiry date

• Metals:

  • have delocalized electron cloud (electron gas)

  • allows atoms to slide past each other under stress

• Ceramics:

  • cant deform plastically due to: ionic & covalent bonds = very strong und directional

  • stress: material fractures

• Bioactive:

  • ability to form bond with living tissue

  • highly reactive in aqateous regions

    -> formation hydroxyapatide layer

• Soda lime silicia glass:

  • windows or bottles

• refers to materials ability to provoke immune response when introduced in body

1. T°C

2. Polymer crosslinking

3. Polymer crystallinity

4. Solvent / polymer interaction

• percentage of solid particles in slurry / suspension

• high in ceramics = improve mechanical properties