Biomaterials Quick Study SheetBiomaterial: (non-viable) material used in a (medical) device intended to interact with a biological systemBiocompatible: Ability of material to perform w/ appropriate host response in a specific application.Elements make up living material: CHNOPSChemical BondsPrimary Bonds: share/transfer of valence electrons (move closer tgt) (ro)= distance of equilibrium (Called Bond Length) Ft(r)= FA(ro) + FR(ro) @equilibrium Ft(r)= total force=0

Covalent: 2 atoms share, rigid bond, big Range Eo=300-700 kj/molIonic: 1 atom donates e-, charged atom, Eo=600-1500 kj/molMetallic: metals not in an ionic enviro, e- sea, Eo =800-900, breakSecondary Bonds: bonds that attach molecules to each otherHydrogen: Eo = 30-50 kj/molVanderWal: Eo = 10-15 kj/molCharacterization of MaterialsStress: 𝜎 = F/A (MPa)Strain(Deformation): 𝜺=𝜟l/lo

Young’s Modulus: E= 2G (1 + 𝛾)Shear modulus G= τ/ 𝛾2 types of failure:1Ductile 2 BrittleStress lower than strength of material with safety factor[Stress] factor: localized substantial increase in internal stress adjacent to geometric irregularityK= 𝜎max /𝜎 nom where 𝜎nom is stress that occurs w/no irregularities

Fracture Theory - energy comes from strain w/in materialEnergy consumed α W*L , W= work of fracture, L= length of CrackEnergy released α W*L2 , acrit = (2Eγ) / (π𝜎c

2)Where E = young (N/m2), γ= work fracture (τ /m2), 𝜎c = Crit stressUntil crack length ‘a’ energy is consumed by system. Crack shorter will not propagate and longer they will.Fatigue Strength and Endurance LimitFatigue= Cyclic loading failureMean Stress: 𝜎m = (𝜎max + 𝜎min) / 2Range of stress: 𝜎r = (𝜎max - 𝜎min)Amplitude of stress: 𝜎a= 𝜎r /2Stress ratio: R = (𝜎max /𝜎min)“S-N curve” (Stress vs Number of cycles)Endurance limit= w/stand ∞ # cyclesFactors affect Fatigue Life:1 [Stress] Factor 2Quality Control 3Material selection 4minimize SCFThermal Properties Specific heat: heat required raise T of 1 unit mass by 1°CLinear Coeff Expansion (α): chnge in unit L in solid if T changes by 1°Volumetric Thermal Expansion Coeff (V): 3*α if isotropic materialThermal Conductivity: q= -k dt/dx, q is heat flux, k is conductivitySurface Properties

Structure & Composition differs from bulk material Little total mass(10-100 nm thick) Unique reactivity leads to chemical rxn (oxidation) Contaminated w/ components from vapor phase

Surface tension: A property due to intermolecular forces, exists in the surface film (layer) of all liquids and tends to bring the contained volume into a form having the least surface area cos θ = (γSV - γSL) / γLV Critical Surf. Tension: Lowest Sur.Ten value of a liquid comp wettingImportant in predicting perfomance of biomaterials and adhesion of cells to surfaces invivo. Low ST = hydrophobic, High ST= hydrophilic.Cell growth-> Hydrophobic. Protien can get in cause cell growth. Monolayers, prevent bacterial adhesion.oxidized metal=hydrophillic Modify Surface propertiesBiological: immoblize biomolecules w/in surface(enzymes,antibiotic)Mechanical:Add texturePhysiochemical: Change chemical comp by alter. With diff composit..Strengthening mechanisms for MetalsSolid Solution Strengthening: Insert atom of different side cause local strain. Large atom under compression, small under tension. Reduce boundary dislocation= ^ Ultimate and yield STR.Grain Size Reduction: grain boundary act as barrier, prevents slip and motion of dislocation. Fine grain = STR and Tougher

σ y=σ o+k

√d, σ y= yeild Str , d=graindiameter

Cold Working-dislocations move and ^ in #, STR & less ductile%CW= ((Ao – Ad)/Ao)x100 , Ao = original Ad= deformedCold Work stainless steel: Screws very cold. Plates want them malleable. Annealing: (1) Recovery (2) Recrystallization (3) Grain GrowthInvestment castingComputer based machiningForgingPowder metallurgic processes*Grinding, polishing3 types of metals used in Medicine

Stainless Steel- (316L) low carbon, (Fe 60-65%), Cr (17-19%), Ni (12-14%)Low carbon- 0.035 weight, b/c more = increased risk of carbides formation (Cr23C6). Carbides = inconsistences in grain, depletes Cr leads to early failure. These are very hard, small particles that will precipitate out of the grains and reside at grain boundaries. At SCF boundary weaken metal. Cr added for oxide layer and Ni stabilizes austenitic phase (FCC) for machining. Good Stainless: (1) Single phase Austenitic (2) grain size ≥#6 (3) uniform GrainASTM Grain Size: N= 2(n-1), N= # of grains in 1 in2, n =grain size <100 micronCobalt Based Alloys: CoCrMo & CoCrWNiASTMF75: (1) Corrosion resistance surface oxide (Cr2O3) (2) Lost wax method (3) “coring”, large grain size (decreased strength) and casting defects (stress concentration)Hot isostatic pressing (HIP)-> sinter powder under P and TASTM F799: hot forging, worked grain struct, 2x yield, UTS and fatigueASTM F90:Add W and Ni to improve machinability, cold work 44% , 2x UTSTitanium Based Alloys: (1) light (2) corrosion Resistance oxide layer (TiO2) (3) Titanium excels in specific strength 2-3 times.ASTM F67 commercially pure (CP) titanium and ASTM F136 extra-low interstitial (ELI) Ti-6Al-4V alloy. impurities such as oxygen, nitrogen, iron, hydrogen, and carbon in varying amounts, which increase strength and reduce ductility. The addition of oxygen increases the yield strength and fatigue life

Disadvantage: low shear STR less desirable for bone screws or platesCeramicsAtoms that are ionocovalently bound, into a much tighter array then metalChemical form : AmXn, Where A is a metal element, X=nonmetalInfluences properties of ceramics : (1) Electronegativity (2) Radius ratiosProperties: Hard Brittle – susceptible to cracks and notches High strength (compressive) Poor conductors of heat and electricity (good insulators) High melting points highly inert (biocompatible) ->Ionic bond b/w atoms do not slip =sensitive to notches &low tensile STR.Test: (1) geometry prep (2) grip w/o fracture (3)0.1% strain align difficultBrittle failure in tensile/compress due to SCF & low strainBend Test: 3 point Vs 4 point(better wider range)flexural strength for 3 point bending is (σF = 3FL/2bd2 where b is the width, d is the height and L is the length of the beam) (four point bending the strength becomes 3FL/4bd2)Processing Ceramics: yield variation of microstructures(1) start powder mixture of ceramic components Forming: powder + h2o+organic binder press into mold(greenware) ^ T, burn binder out (bisqueware) densify cooling + polishing Liquid Casting – Powder is heat melting T mixture is homogeneous. Liquid is then cast to form the shape of object. glassy or polycrystalline structure. Vitrification (liquid phase sintering) – Powders are formed into the shape of the desired object and fired at high temperature. This forms a liquid phase that upon cooling becomes a glass-bonding matrix.Types of Ceramics Nonabsorbable or Relatively Inert Bioceramics Maintain physical and mechanical properties in the host. *Used structure support implants (i.e. bone plates, screws, dental implants) Also ventilation tubes, sterilization devices and drug delivery devices. 1.Alumina (Al2O3) (hip prostheses (socket) and dental implants) Hardness 2300 kg/mm2 or 9 on Moh’s scale, strength (compression 4500 MPa, bending 550 MPa) Low friction and wear (advantages for use as joint replacement) prepared with a seed crystal at high temperatures 1600-1700 degrees C, then feeding fine alumina powders on the surface, pressing and sintering Strength dependent on porosity and grain size 2.Zirconia (ZrO2) (articulating ball in total hip, dental implants) Lower modulus of elasticity than alumina, higher strength Superior wear resistance to UHWPE Biodegradable or Resorbable Ceramics1. Calcium Phosphate or Hydroxyapatite (used as artificial bone)degrade within host at the same rate that host regenerates new bone. problems including maintaining the strength during degradation and matching the two rates (degradation and growth).*Numerous applications: drug delivery, bone replacement, coating on implants for porous ingrowth Excellent biocompatibility Elastic Modulus (40-117 GPa), compared to enamel (74), dentin (21), and cortical bone (12-18) GPa Bioactive or Surface Reactive Ceramics – Glass-ceramics*form a direct chemical bond with the host tissue. Glass ceramic is crystallized in a controlled environment, resulting in the precipitation of purposely-inserted metals that help nucleate the glass and form an extra fine-grained structure. Compositions for implantation applications include SiO2-CaO-Na2O-P2O5 and Li2O-ZnO-SiO2 systems four types of tissue response and attachment: Type 1 – dense, nonporous inert implants attach by bone growth into surface irregularities through press fitting – termed “morphological fixation” Type 2 – porous inert implants result in bony ingrowth that mechanically attaches to the implant – termed “biological fixation” Type 3 – dense, nonporous, surface reactive ceramics and glass ceramics that attach to bone through a chemical reaction – termed “bioactive fixation” Type 4 – dense, nonporous or porous resorbable ceramics designed to be slowly replaced by boneDeterioration of CeramicsFatigue strength is reduced by water. Imperfections allow permeation of water molecules. Imperfections source of crack propagation. Test larger than expectTmin = Bσp N-2 σa-N or Tmin * σa2 =B(σp/σa) N-2Tmin – is the minimum lif, B,N – empirical constants, σp, σa – proof stress and applied stress respectivelyPolymershuge MW from long backbone chain. Varying properties, defined by MW, L, backbone structure, side chains and crystallinity. covalent bonding along backbone. chains are held together by 2ndary bonding forces or covalent bonds between chains = additional str. chains are flexible .prepolymer : growing towards many units. oligomer – few units fixed in size. homopolymer – polymer of fixed mer type. copolymer – polymers of 2 mer types (random, alternating, block). heteropolymer – polymers of many mer typesDegree of Polymerization (DP)= an average # of mers per moleculeMW of polymer = DP * MW of the merNumber average Mn =Σ NiMi/ΣNi, (1st moment of MW distribution)Weight average Mw =Σ NiMi2/ ΣNiMi, Ni =# molecules with DP”I”, Mi = MW of “I”Polydispersity Index(PI):ratio of Mw to Mn. Note that if PI =1, Mn = Mw, meaning all molecules have equal length (monodisperse). only in natural

proteins. Synthetic polymers in biomedicine have 1.5<PI<5.0 (polydisperse).Propertieslower elastic modulus, yield and ultimate properties. a greater post-yield deformability before breaking and much larger strains before failure. They also display characteristic fatigue properties. Short polymers= plasticizers^ MW = STR + Stiffer, b/c chaines longer and less mobileChange backbone to carbon to oxygen = ^ flexibilityFactors affect Mechanical Properties 1) MW of the “mer” 2) Degree of crystallinity-higher crystallinity = str solid 3)Drawing – analogous to coldworking – material becomes stronger in the direction of the draw, anisotropic 4)Chemical composition of the backbone 5) Heat treating – leads to increased E, strength and decreased ductility.

Tacticity – the arrangement of the side-chains around the backboneIsotactic – all side group same sideSyndiotactic – Side groups are on alternating sidesAtactic – R groups are randomly distributed

1. chains unfolding2. chains slide (Plastic deform)3. bonds stretch4. Bonds Stretch and Break

Polymer Synthesis1) Addition Polymerization: Initiation (radical), Propagation, termination2 Condensation Polymerization: 2 monomers react, water is releasedThermal Properties

“melt” state, long segments randomly move =Brownian (random) motion.Motion stops at (Tg) glass transition temperatureBelow Tg, polymers are hard and glassy, and above Tg they are more rubbery.Thermosetting- polymers become permanently hard with applied heat due to the formation of covalent cross-links between polymer chains. Harder , less ductile.Thermoplastic- (Tg) above, 2ndary bonds break reversible changes. Rubbery state allows more ductile but weaker Above Melting temperature (Tm) -1ary bonds broken, irreversible changes CompositesFabricated to provide desired mechanical properties such as strength, stiffness, toughness and fatigue resistance. Composites consist of a matrix, and a reinforcing material (either particle or fiber). Expose fibers or particles to the surrounding biological environment. Possibility of cellular ingestion of particulate debris exists

(tissue reaction). composite to be called biodegradable, it must fully degrade in a specified duration of time under given environmental conditions (these conditions specify pressure and temperature

Reinforcing Systems of Composites The main reinforcing materials that have been used in biomedical composites:Carbon Fibre: (1) Lowdensity (1.7-2.1 g/cm3) (2 )High mechanical properties: (E up to 900 GPa, ultimate strength up to 4.5 PPa) Polymer Fibres: (1) Can be made absorbable (2)Aramid fibers are strong in tension (examples Kevlar,Nomex) (3) Concerns with biocompatibility Ceramics Particulate composites, poor strength in tension or shear. Mainly used in bone enhancement applications Glasses:High strength to weight ratio, stable and easily fabricated. Low costMatrix Systems Most biomedical composites have polymeric matrices, mostly thermoplastic, either bioabsorbable or not. The most common matrices are synthetic nonabsorbable polymers.

BioEthicsHuman Clinical Trials vs Animal Trial-Hard to do blind with human subjects, placebo vs implantEX: controlled trial of arthroscopic surgery of the knee (no benefits)-standards for humane treatment of animals Minimize through Computer models and tissue culture testingIndustrial Support for ResearchSuppressing Data, Prevent FDA Approval of new device, Study failuresRegulation of Medical DevicesBased on use and relative risk, reference ISO standards (ISO 13485 “quality management systems- medical devices- system requirements for regulatory purposes”)CLASS 1: low risk, short term insert in body, skin contact (tongue depressor)CLASS 2: Medium risk, short term invasive contact (Needles, Orthodontic)CLASS 3: high risk, longer term,energy delivery (sutures, catheters, dialysis)CLASS 4: Highest risk (Pacemaker, blood glucose, breast implant, heart valve)-(75% of class I are exempt from regulation “substantially equivalent to an old, exempt device “Grandfathering”)- Class III requires PreMarket Approval (PMA)- evidence of safety and effectiveness, public hearingsLegislation and LitigationDow Corning Silicone Breast Implant-1960 plastic surgeon silicone breast, 1976 FDA “Grandfathered”, status change to CLASS 3, Provide PMA, 440,000 women connective tissue disease, localized problems but not autoimmune diseases (lupus, arthritis )DuPont Teflon (TMJ implants)Vitek-Temporomandibular joint replacement- 1998 Biomaterials Acess assurance ActBiological Tissues

Natural Materials (Bone-reservoir of calcium and phosphate)5 classes of bones: long(femur), short (tarsus), flat (skull), irregular (hip) and sesamoid (patella).

Microscopic Level: Cortical (compact 0.7-0.95 g/cc) & trabecular /cancellous/ spongy bone (0.05-0.7)Hierarchal Structure of Bone:Layer 1: Osteoid Collagen type 1 (90%), Proteoglycans- glycosaminoglycan & glycoproteins (10%), Mineral Salts (hydroxyapatite), extracellular matrix. More ductile than hydroxyapatite but more rigid than collagen (^ str and stiff)Layer 2: Lamella Sheets 4 arrangements(1)Array Parallel Fibers- to long axis, Anisotropic – lay fibrils to optimize mechanical function. Not highly vascularized .High modulus = 26 GPa in direction || to fibres(2) Woven-Disordered, not isotropic, common after fracture and formation of new bone quickly, in embryos(3) Plywood- discrete parallel layers. Orientation of layer is different. Similar to laminated composite, different layer thickness (thin and thick repeats). Most common bone type. Extent of Anisotropy is not as high as array parallel fibers. Resist compressive strength in many directions unlike || -> optimized for one direction.(4)Radial Fibril Arrays- Fibrils oriented in planes concentric around blood vessels (dentin, teeth)Layer 3: Haversian Canal/ Osteons

Remodeling of bones to optimize structure based on Load history. Catabolic/ anabolic coupling tunnel excavation by osteoclasts and lamellar bone laid by osteoblasts in concentric layers fill core until small lumen left

as blood vessel. Bone Cell Types:Osteoclasts: Large multinucleated cells. Affix to the bone interface and seal it off to nearby environment. Acidify the enclosed microenvironment and dissolve organic and inorganic compounds of bone. “breakdown”Osteoblasts: Derived from stem cells in the marrow, periosteum & soft tissue. They secrete osteoid and mineralize it to make new bone. “build”

Osteocytes: Reside permanently in and on the bone. “maintaining” cells.Layer 4: Cortical and Trabecular BoneSpongy/Cancellous Bone: highly porous High concentration of blood vessels and cell-to-bone ratio Low density Low mechanical properties, weak, High surface areaCompact/Cortical Bone: Less porous Few blood vessels and low cell-to-bone ratio Higher density Greater mechanical propertiesProperties of Cortical Bone

Forms most of the shell along the diaphysis of a long bone. Anisotropic- properties are dependent upon the orientation of the applied load. Generally, cortical bone is strongest along the long axis of the bone with an ultimate tensile strength of approximately 180 MPa. In contrast, the tensile strength in the tangential and radial directions are 70 MPa and 30 MPa. The strength is dependent upon the orientation of the lamellar sheets as discussed in layer II.

The lumens of the osteons and vascular canals running radially through the bone may act as potential stress concentrations. In Longitudinal direction: holes have minimal effect σ= F/AIn radial direction holes significant effect: kt=1+2(a/b)

Properties of Trabecular BonePrimary difference between cortical and trabecular bone is porosity or density of the bone. Apparent

density of bone:

no haversian canals but bone is deposited in longitudinal layers. Cancellous bone has significantly lower calcium content than cortical. Significantly higher water content than cortical -> more active in remodeling and less mineralizedCompressive strength of trabecular bone and compressive modulus is related to apparent

density by power laws: σ= 60⍴2 and E= 2915⍴3

Trabecular bone is composed of short struts called trabeculae. Very small changes in pore size/density of trabecular bone, the strength also changes exponential. Struts deteriorate with age. As we age (1) reduction in # trabeculae (2) reduction in thickness (3) increase in length

Pcrit=π2 EI

L2 , I=π4

I 4(circular cross section)

When L increases critical load for buckling decreases. Therefore it’s more likely to buckleBiomechanical Testing of BoneExperimental Factors: (1) Specimen preparation (2) Specimen preservation- 1) Chemical Fixation and 2) Freezing. Formalin denatures proteins and prevents lysis, de-thawing problems (3) Hydration- Dry Samples: ↑Young’s Modulus (E), ↓Strength, ↓toughness Wet Samples: ↓Young’s Modulus (E), ↑Strength, ↑toughness (4) Temperature-body temperature (37°C)-(23°C) increases E by about 2-4% (5)Strain Rate- ↑bone strength approx. 15%. (6) method testing- tensile vs compressiveBiological Factors Affecting Bone Strength: Age of donor - peak bone mineral density at around age 30 and strength decreases about 2% per decade after. Disease – osteoporosis Gender - women less bone mass & steeper decline after age 50 due to menopausal. Activity level – remodelling is triggered by repetitive loading Structure of Ligaments and Tendons