MSE 3611 Midterm 3

type III applications

hydroxyapatite -original bioactive bioceramic, chem of bone -used in dental implants, orthopaedic coating, tympanic implants dislocation seen in 20% alumina implants and 2% HA implants -alumina type I, not form bond -HA, natural bond to surrounding tissue

bioceramic chemistry

interaction with the surrounding tissue will depend heavily on chemistry and structure, some chem have good bond common ceramic chemistries -hydroxyapatite, bone -calcium carbonate, coral -calcium sulfate, plaster -tricalcium phosphate -zirconia, ortho -alumina, ortho -bioglass -carbon

bone remodeling (2)

key signals and hormones -mechanical strain, promotes bone formation -lack of mech forces, increased osteoclastogenesis, responsible for resorption, no blocking sclerostin

osteocyte lacunae and canaliculi

lacunae -holes (10-20) um in bone where osteocytes site -osteocytes get trapped within the bone during he mineralization process canaliculi -small tunnels connecting lacunae -cell-cell communicaiton, mech/chem, coordinates adaptation process pic lec 17

hot isotonic pressing

sim to SSS but add pressure, simple shaped product pressure added during densification under heat

determining MW and PI experimentally

size exclusion chromotography is often used to measure molec weight and PI sm -> diffusivity high, at bottom large -> less distance

controlled drug delivery

sustain drug -maintain const effective drug level in body -avoid undesirable side effects assoc with sawtooth kinetic pattern localized drug action -place drug delivery sysem in or next to diseased tissue/organ target drug action to specific cell -carriers or chem derivatization to target specific cells

common systems/release rates

systems which an provide some control of drug release in the body -temporal -spatial -both -specifically release rate/duration in vivo by simple in vitro test prolonged or sustained release systems are not controlled release systems by this definition

alumina

-highly stable oxide -chem and bioinert -low fracture toughness and tensile strength, no long bone, high compressive strength -high hardness (20-30 GPa), high wear resistance -used for dental implants, orthopedic implants (articulating surface), vertebrae spacers, implant coating, used in compression/articulating surfaces

polydispersity

-Mn treats all polymer chains equally -Mw gives more emphasis to larger chains, mech prop are commonly more closely related to Mw than Mn -to quantify molecular weight homogeneity polydispersity is often calculated PI = Mw/Mn, smallest PI = 1, as PI increases, braoder distribution of MW high MW = tougher short chain = easier to get flow, weaker viscosity UHMWPE, no injection molding, compression molding

polymer structure (lec 19 fig)

-in addition to conformation and config -polymer structure -linear, bifunctional mer -branched, trifunctional mer -crosslinked (tri) -network, tri

polymer synthesis

-based on probability, what you run in rxn chamber -chain length controls prop addition polymerization -chain reaction -unsaturated monomers react, double bond present 1. INITIATION, free radicals, cations, anions, catalyst, open up double bond, creates initiation site on monomer I-I -> 2I I dot + M -> M dot or R dot creates open bond, interacts with monomer, creates monomer that can react, need to break down double bond in monomer 2. PROPAGATION, rapid chain growth unreacted bond still there Rj + M -> Rj+1 OR Mj + M -> Mj+1 3. TERMINATION, rxn with another radical, rxn with solvent molec, fragment of polymer Mj dot + Mx dot -> Mx+j OR Mx + Mj (double bond) condensation polymerization -stepwise growth two monomers react to form covalent bond -elimination of small molec, water, co2 (generate mores) -diacid + diol example in notes (lec 20) synthesis method -strongly affects polumer obtained -Ex free radical polymerization (addition poly), based on probability, MW more diff to control, MW distributed broadly, branched products possible -Ex anionic polymerization (addition poly), lower PI, narrow MW distribution, regular linear chains addition polymerization -homopolymer -copolymer, A-B-A-B, random alternating or block; random - prop weighted avg; block - prop are unique to both, regions condensation -homo and copolymer -co polymer depends on type of monomer, mw of product, disribution of MW (PI)

fucntionality

-bifunctional, bond to add her on both ends, linear -trifunctional, 3 active bonds that can bind to other mers, branched -may result in network polymer -network (strongest) polymer, covalent bond btwn all chains

osseointegration

-biolog response -bone growth up to/into the surface of the implant without soft tissue at the interface -when bioceramic like calcium phosphates are implanted into the body ow does he bone bond -> HA layer -what mech prop/zones are created -how do we encourage new bone formation -> regenerate tissue, quality

osteonal bone

-blood vessels surrounded by concentric rings of bone tissue -primary osteonal bone, formed from existing collagen, less lamellae, sm number of rings, vascular channels smaller -secondary osteonal bone, replacement of existing bone, will include interstitial bone picture lec 17

plasma spray

-ceramic powder introduced into plasma jet ->10000K, melts powder fast -powder - melt and propelled toward surface/substrate -droplets hit substrate, flatten and cool -applications: coatings on preshaped parts -complications: diff to control, coating composition and microstructure can vary across surface (lateral), gradient from surface outward, product varies, vendor, clinical inconsistency makes metal warmer -> metal on ceramic to ceramic on ceramic and change temp as build -> diff microstructure

summary polymer B

-chemistry and macrostructure affect polymer prop -mech testing highly dependent on testing conditions -large array of bme polymers, surface prop, philic/phobic, mech pro, degradation rate

bone structure: irregular bone

-complicated shape, does not fit into prev category -composed of spongy bone and marrow covered wit compact bone -ex: vertebra, hip bone

slip casting

-decrease porosity, change in volume decrease -prepare slurry or slip, powder and dispersing agent -pour slip into mold -condensation of slip into mold wall, drain, fire -low porosity -fewer defects and higher toughness than many other methods -complex shape, since change in volume can be bad for med device

bone structure: long bone

-diaphysis: compact bone collar over marrow-filled medullary cavity -epiphyses: bone ends, compact over spongy, articular (hyaline) cartilage; epiphyseal lime (remnant of epiphyseal plate) -membrane: periosteum (rich in SC, vascular), endosteum (SC), compact over spongy

conventional methods of drug delivery

-external - intestinal -all other routes considered parenteral

type I

-high compressive strength. resistant to wear -failure loads 10-50 times body weight -high resistance to compressive deformation, resist wear -high hardness -ideal for coupled application, hip implant, biolox fem head

steps in solid state sintering

-initial: particle smoothing, grain boundaries form, necks grow, pore rounding, porosity decreases <12% -intermediate: shrinkage of open pores, more intersecting grain boundaries, mean porosity decreases significantly, slow grain growth -final (1): closed pores, containing furnace has form when density reaches ~92%, closed pores intersect grain boundaries, pores shrink to a limited size or disappear -final (2): grains of much larger size appear rapidly, pores within large grains shrink slowly

PPF - polypropylene furmarate

-linear, unsaturated aliphatic polyester -undergoes biodegradation via hydrolytic cleavage of ester linkages -propylene glycol and fumaric acid, degradation products, both are non toxic, readily removed/utilized -with a few repeat units (n), PPf is viscous yellow liquid at RT -as molec weight increases via optical methods, eventually becomes a solid "plastic" -Mn = 1460 +- 200 g/mol (PDI 2.6)

factors that influence drug delivery rate: system

-mat solubility -swelling -molec weight, control release rate -crystallinity -phys stability, degradation -protein binding

implant-tissue response

-material toxic - surrounding tissue dies -material nontoxic and biologically inactive - fibrous tissue formation, type I -material nontoxic and biologically active - interfacial bond forms material nontoxic and dissolves - surrounding tissue replaces it, degraded and replaced

polymeric drug delivery system

-matrix, within polymer structure itself -reservoir

calculating percent crystallinity

-never 100% -crystalline regions more dense, up to 20% -calculate density of sample, ps -known density in full amorphous, pa -known desnity in almost fully crustalline, pc (pc(ps-pa)*100)/(ps(pc-pa)

woven cortical bone

-no osteons -can be formed de novo, doesn't need existing cartilage or bone -found in young skeletons, less than 5 years old -adults: disease, injury, fracture -most disorganized structure -most osteocytes -mechanical prop: weaker than normal cortical bone -dashed/stripes: fibril of collagen -disorganized, deposited faster

new design

-not randomized which leg got implant, so randomize in new study, random site assignment, stratefied -control mat: marmal HA, diff sizes/quantities of porosity how might you alter the implant -composite mat, HA, TCP -slow degrade and high strength polymer, high strength in regeneration/degradation -Ti foam

molecular weight (lec 19 fig)

-one way to represent number of mers/length of each polymer chain is use degree of polymerization, repeat units to make chair -polymer size can also be described in terms of molecular weight -not all chains are exact same length, diff (n) in chain -molecular weight of each repeat unit (math problem lec 19) -distribution of molec weight formed during synthesis -average molec weight -number average molec weight (Mn) -weight average molecular weight (Mw) number average - equal value to all chains Mn = sum(Xi*Mi) Xi = Ni/(sumNi) Mn = sum(Ni*Mi)/sum(Ni) Ni = number of chains with the molecular weight Mi Xi = number fraction of molec weight Mi = avg molec weight for the chosen molecular weight range weight average - more importance on larger chains Mw = sum(wi*Mi) wi = Wi/sum(Wi) Mw = sum(Ni*Mi^2)/sum(Ni*Mi) Wi = moass of chains with the molecular weight Mi (also = Ni*Mi) wi mass fraction of molec weight Mi = average molec weight for the chosen molec weight range Mw >> Mn

configuration (lec 18 fig

-part of the structure of molec that cannot be changed without breaking a bond isotactic -all side groups evenly spaced on same side of polymer backbone syndiotactic -side groups uniformly spaced on either side of polymer backbone atactic -side groups arranced in random manner configuration - how easy it is to fold polymer C-C double bond -double bond reduces number of possible conformations -also controls possible configurations, reduces -cis structure, both side groups are on eh same side of double bond trans -side groups are on the opp side of double bond -cis and trans structures have vastly diff mech prop -bond has to break to change -given polymer chain may contain mult configurations, predominant config is primarily dependent on synthesis method -from these example polymers it is clear that bond must be broken to change config -switching conformation only requires rotation

processing methods

-plasma spray -solid state sintering -hot isotonic pressing -slip casting -rapid prototyping (SLS)

summary: polymers

-polymer- long chains of covalently bonded hydrocarbons -mer - smallest building block of polymer, repeat units -degree of polymerization - number of building blocks -large variation in mech and chem prop, greatly dependent on conformation, configuration, and overall structure

general structure

-polymers are comprised of repeat units called mers -mer - structural entity made of a fixed number of atoms in a given structure that is repeated to form a polymer -monomer, molec containing only one mer -oligomer, molec containing 2-10 mers repeat units can be -saturated, each C on mer bonded to 4 other atoms, polyethylene -unsaturated, 2 of C in mer are bonded with a double bond -affects crystallinity, folding affects crosslinking, available are bonds to bond to adjacent poly chain

structure of polymers

-polymers, also called macromolec, 10^5-10^6 g/mol -synthetic, nylon, polyethylene -natural, collagen, chitosan, leather -can be amorphous, crystalline, or semi crystalline

rapid prototyping

-predictable porosity -a lot of pore sizes and structures binder -to build up part, powder stick in only specific locations -still have to SSS laser -laser 3D print, sinter while building

bone development: msc derived (figure lec 17)

-prob and environ included, msc cluster into ball diff into osteoblast, lay down osteoids -> lay down matrix -> mineralized 1. ossification center, appears in fibrous connective tissue membrane, selected centrally located mesenchymal cells, cluster and differentiate into osteoblasts, forming as ossification center 2. bone matrix (osteoid) is secreted within the fibrous membrane, osteoblasts begin to secrete osteoid, which is mineralized with a few days, trapped osteoblasts become osteocytes, make bone 3. woven bone and periosteum form, accumulating osteoid is laid down btwn embryonic blood vessels, which form a random network. The result is a network (instead of lamellae) of trabeculae, vascularized mesenchyme condenses on the external face of the woven bone and becomes the periosteum, mineralized around existing blood vessels -> woen bone with vascularization 4. bone collar of compact bone forms and red marrow appears, trabeculae just deep to the periosteum thicken, forming a woven bone colar that is later replaced with mature lamellar bone, spongy bone (diploe), consisting of distinct trabeculae, persists internally and its vascular tissue becomes red marrow, porous bone thicken and become compact bone

side groups

-size - if large and bulky, prevents neighboring chains from coming close enough to form crystalline structure, polystyrene, bulky side group -location - atactic (random) polymer more difficult, prevents neighboring chains from folding in ordered fashion, , same idea for copolymers

factors that influence drug delivery rate: drug

-solubility -partition coef -molec weight -chem stability, processing, how long is it stable, shelf stability -physical stabiliyt, processing, how long is it stable, shelf stability -protein binding

solid state properties

-tacticity, how individ chain prop control -crystallinity, how individ chain prop control, controls mech, degradation/swelling; crystallinity -> R, folding, MW; long chain - gets tangled up; short chain - a lot mroe motion so harder to corral; mid length more ideal for folding -thermal prop -mech prop

bone structure: short bone

-thin layer of compact bone surrounding spongy bone -low density, high flexibility

bone structure: flat bones

-thin periosteum covered compact bone on outside -endosteum covered spongy none on inside -no diaphysis or epiphysis -bone marrow fills space btwn trabecular -thin periosteum covered, good at resist compression

bone development

1) msc derived, bone marrow sc 2) from existing cartilage

bone development: from existing cartilage (fig)

1. formation of bone collar around hyaline cartilage model, ossify along diaphysis 2. cavitation of the hyaline cartilage within the cartilage model, cavity, epiphyses 3. invasion of internal cavities by the periosteal bud and spongy bone formation, blood vessels, osteoblast precursor 4. formation of medullary cavity as ossification continues, appearance of secondary ossification centers in the epiphyses in preparation for stage 5, more blood vessels 5. ossification of the epiphyses, when compleded, hyaline cartilage remains only in eh epiphyseal plates and articular cartilages, line because 2 distinct bone formation

implant-tissue interface

4 major types of interaction defined by -bioreactivity, chem -tissue ingrowth, chem and shape

chemsitry: bone vs soft tissue (picture lec 16)

A: good bond to bone dashed: good bond to soft tissue B: intert, fibrous capsule C: high degradable, resorbable D: not practical for bme use change chem to change biolog response

quantifying thermal prop

DSC can provide -Tg - heat capacity, increase an energy is absorbed by chain rearrangement -Tm - peak endotherm heat flow -assess structural prop -area under Tm endotherm proportional to percent crystallinity how thermal relate to structural -measure struct by thermal heat flow -double oven -reference sample -maintain unknown sample at sam etemp as reference -measure power needed to do this, keep both at same temp heat flux -single oven -measure temp diff betwen sample and reference -less accurate, slower, less sensitive, less expensive

bone remodeling (fig)

growing shaft is remodeled by 1. bone resorbed here 2. bone added by appositional growth here 3. bone resorbed here

maintaining drug action

half life -many drugs have short half life -ampicillin - 100 min -penicillin - 45 min -require significant conentration to remian effective -maintain activity by taking multiple doses

replacement

heat wood under Ar -leaves behind only C template infuse C template -Si melt -forms SiC at higher temps -lose some porosity but have original structure of wood -small interconnected channels with large pores

Solid state sintering: thermodynamics

GT = Gv + Gb + Gs reduction in free energy Gv = volume free energy, increase Gb = grain boundary free energy, decrease, merging particles and growing them Gs = surface free energy, decrease, merging particles and growing them -layered in with other manu tech, mold, printed pores shrink -> much less pores, dont get 100% densification

classes of polymers

homo polymers copolymers nonresorbable bioresorbable

bme polymers: non resorbable homopolymers

PMMA - polymethylmethacrylate -plexiglas, lucite -hydrophobic -clear -tough -applications: hard contact lens, bone cement 2-hydroxyethyl methacrylate, HEMA -hydrophilic -clear -soft -crosslinked to resist degradation -contact lens -philic -> hold moisture there, ride on film of liquid high density polyethylene, HDPE -hydrophobic -tough -inexpensive -application: tubing, drains, catheters, UHMWPE -> acetabular cup polypropylene PP -high rigidity, semi crystalline form -chem resistance -good tensile strength -applications: simialr to PE, storage container (conical tubes), tubing (more rigid), doesnt stick to tissue (wound dressing, mesh) polytetrafluoroethylene PTFE -gortex, teflon -very stable -diff to process -hydrophobic -low coef of friction -applications - vascular graft -high Tm, diff to process polyvinylchrloride, PVC -hard -brittle -can be soften with plasticizers, easier to slide past each other, plasticizers can be eluted int the body -applications - tubing polydimethysiloxane PDMS -extremely flexible -low Tg -applications - catheter, tubing, insulation, blood vessels heart valve, cosmetic surgery

mer conformation

each macromolec can take on a wide variety of diff shapes -in contrast to metals and ceramics where atomic structure is largely based on chem -C-C-C bonds in backbone not strictly linear, 109.5 degrees -folding of polymer chain -C can rotate along this 109.5 bond allowing polymer to bend and fold back upon itself, cone (3D space) -chem of backbone and size of side groups affects conformation -conformation, part of the structure that can be changed by rotation about a single bond -lowest energy in coiled state, rotate bonds to get diff conformation

second level structure

secondary level - what makes up the osteon osteon -lamellae - rings/layer -osteocyte lacunae -osteocyte canaliculi -cement line

properties

selection based on desired -stability -tissue response -mech prop needed

Conformation (lec 19 fig)

easiest to hardest bending and rotation easy - polyethylene middle - polystyrene, large side group hard - polyisoprene, double bond doesnt allow rotation lec 19 figure

calcium phosphates

apatites -least soluble of calcium phosphates -general formula: M10(ZO4)6X2 M = Ca, Sr, Ba, Cd, Pb, Mg, Na, K, H Z = P, CO3, V, S, Si, Ge, Cr, B X = OH, CO3, O, BO2, F, Cl Ex: Ca10(PO4)6(OH)2, hydroxyapatite vary alloy, very strongly alters prop if add/remove just 1% stability -dependent on temperature and presence of water, body temperature (Stable (dicalcium phosphate, hydroxyapatite)), higher temperature (tricalcium phosphate (TCP), not stable at body temperature and degrades, tetracalcium phosphate, stable) -unhydrated high temp calcium phosphate phases, form HA at fluid exposed at surface of body, make direct bond to bone bonding mechanism -bone bonds to HA layer, bulk or surface -osteoblasts at junction, produce bone matrix with collagen-osteoid, 3-5 microns wide, thin layer, bond matures and interface shrinks (0.05-0.2 microns), perfect epitaxial alignment of bone crystalites with apatite crystalites in implant, cystals line up perfectly with ceramics, gradient in mech prop of very high: sharp gradient, site of fracture (solid ceramic to bone(, want to use porous ceramic HA: remodeled by normal (slow) osteoclasts TCP: degradable, rapid turnover

drug delivery

better targeting -spatial targeting of drug -temporal targeting of drug reduce discomfort of patient if need constant injection ability to reposition drug within market, change how delivered long lasting biotherapeutics direct cell funct in healing or forming tissues

examples of type III

bioactive glasses -bioglass - larry hench, original composition glass + bone (Ca/P final Ca/P ratio 5:2 bioactive class-ceramics -ceravital dense HA -durapatite -calcitite bioactive composites -HA-PE HA-bioglass keep bulk but change surface prop

type III

bioactive mat -intermediate - btwn type II and IV -elicits a biological response at surface that encourages formation of a bond btwn tissue and mat, expanding field, wide array of bonding and thicknesses of bond can be achieved -HA bonds directly to bone -not degrade fully, hold mech prop and bonds

summary of ceramics

bioglasses/bioceramics -approx some aspects of bone chemistry -stability depends on chem of ceramic, temp and pH of fluid -formation of HA layer on bioglasses and bioceramics aid in bone bonding processing methods -require high temp -cam be tuned to provide complex geometries

bone replacement

bone autograft -stem cell pop -bone -> same architecture, same material components

bone growth (figure)

bone grows in length because 1. cartilage grows here 2. cartilage is replaced by bone here 3. cartilage grows here 4. cartilage is replaced by bone here change in thickness around collar

summary: bioceramics for bone

bone is classified by location and shape bone hierarchical -two main macro-structures: compact and trabecular -microstructure --cellular: osteoblasts, osteoclasts, osteocytes, osteogenic progenitors --materials: collagen type I and mineral (hydroxyapatite) development and growth -complax coordinated action

bone remodeling

bone is dynamic and active tissue small-scale changes in bone architecture occur continually activation -detection of initiating signal by osteocytes, mech strain, hormone action -damage to matrix or immobilization cause osteocyte apoptosis -increase osteoclastogenesis resorption -osteoclast respond to signals from osteocytes, recruit osteoclast precursors -cytokines released induce osteoclast formation, osteoclast activity -osteoclasts seal to bone, digest mineral, phagocytose remnants reversal -undigested, demineralized collagen removed, osteoblast lineage cells adhere -details of transition not well understood formation -mech stimulation and endocrine signaling, osteocytes normally produce sclerostin, prevents Wnt signlaing, bone inducer, mechanical strain blocks production of schelostin, results in bone production -osteoblast progenitors return, differentiate into osteoblasts, secrete molec that eventually become bone' -want Wnt signaling, bone formation -osteoids -> becomes bone

bone structure: microscopic

cellular components -osteogenic cells (stem line), develop into osteoblast -osteoblasts, forms bone matrix -osteocytes, command center, maintains bone tissue -osteoclasts, remodel/resorb, breakdown of bone matrix constituents -collagen -mineral - Hydroxyapatite hierarchical structure

bones

classified my -location: axial vs appendicular -shape: long, short, flat, irregular functions of bone -support -protect -movement -storage - minerals, growth factors, fat -hematopoesis compression, tension, torsion

bone structure: macroscopic texture

compact (lamellar) bone/cortical -low porosity -appears smooth from teh naked eye cancellous (spongy bone)/trabecular -trabecullae -high porosity (40-95%) -red or yellow marrow, age dependent red-> flat bone decreases into adult yellow -> fatty marrow

structure of spongy bone

complex -multiple layers of structure ranging from few microns to hundreds of microns, collagen and HA -multiple material types, HA and collagen -very difficult to engineer in a bottom up approach -distinct hierarchical structure

crystallinity and polymeric mat

crystallinity, key phys prop of polymers -percent crystallinity varies in polymers far more than metals or ceramics -large number of molec in polymer cell -unit cell is very complex -little symmetric, large percent crystallinity -dependent on chem structure of mer and polymer config -mer side group -chain branching -tacticity -regularity of mer placement in copolymer

ideal drug delivery systems

deliver drug at rate which matches needs of body -when glucose level drops, delivers appropriate amt of glucose to return to baseline deliver drug to active site only (cell, tissue, organ) no drug delivery systems do both, diff to manage

cortical bone organization

dense compact bone -level 0: solid mat, macro -level 1: primary osteonal bone, secondary osteonal bone, intersitial bone, plexiform bone -level 2: lamellae, lacunae, cement line -level 3: collagen-mineral composite as levels increase zoom in more layers of organization

types of ceramics, glasses, glass-ceramics

described in terms of biological response type I - bioinert/nearly inert -no chem or biological bond at T-M interface, can have adherence of tissue/bone to surface irregularities, implant cemented or press fit into surrounding tissue, morphological fixation -relative movement, controls capsule formation -development of fibrous capsule around implant, ex: alumina more movement -> thick capsule

autograft bone harvesting

disadvantages to autograft -secondary wound site, infection of harvest site -painful procedure -finite available for use, limited supply

replacing bone

disease and injury may require the replacement of bone can be repalced with -autograft, sm size, cellularized, vasculature, donor site morbidity -allograft, decellularized human tissue, difers from location, variation -bioceramics advantages/disadvantages

bioactive glasses

distinguished by ability to bond to bone and/or soft tissue -form carbonated HA layer upon implantation, mediate bond to bone chemistries known to bond to bone -SiO2, Na2O, CaO, P2O5 -specific proportions, >60% SiO2 (silica), high Na2O and CaO content, high CaO/P2O3 ratio coatings on bulk mat to increase bonding to bone, used as bulk if need high mech prop instantly bioglass 45S5 most common, orig bioglass

chain fold models of crystallinity

lamella -basic unit of crystal structure -larger than unit cell -polymer chains folded back on hemselves, 3D pattern -highly idealized -tightly packed in one plain -chains of polymer -crystals not as uniform in reality, mult chains within them, amorphous regions within lamella -crystallizaton from melt, from spherulites, 3D aggregates of lamella

second level structure (2)

lamellae -3-7 um thick layers of bone -oriented concentrically around haversion canal -contain collagen and mineral, HA

synthetic bone graft

location and anatomy determines chemistry and physical prop

polymers

long chain of molec natural polymers -chitosan -collagen -cellulose -dna -natural rubber sunthetic polymers -PE -PS -PLA -PGA -PLGA -PCL

mechanical prop

mechanical testing highly dependent on test conditions -temo -> high temp decreases E, more deform -strain rate noncrystalline polymer -chains sliding past one another -breaking and reforming H bonds, weak interaction -no preferential direction of motion, in contrast to crystalline mat semicrystalline polymers -contain spherulites, packets of lamella -amorphous regions in between exposure to tensile force -tie chains exend and lamella slide past eachother -lamella become reoriented, chain folds aligned along axis of loading -blocks of crystalline phase become separated from one another -blocks and tie molec oriented along axis of applied tensite force -start to unravel fracture along the chains

Ceramics, glasses, glass-ceramics

medical industry -diagnostic instruments -carriers for enzymes, antibodies, anitgens -crowns -articulating surfaces -scaffold/filler for bone repair -porous bioceramic scaffolds -wear rate -alumina on alumina materials design -composition -microstructure -phase state -surface -shape

thermal prop

melt/liquid state -thermal energy - random chain motion -cool -> temp is reached where chain motion stops; glass transitional temp (Tg); varies from polymer to polymer -polymer below Tg is hard and glass polymers above Tg -> rubbery polymers with crystallinity -melting temp (Tm), increase cryst, increase Tm -melting of crystalline phase measured by -differential scanning calorimetry (DSC) -viscoelastic response Tg determines mech prop

regenerating bone

multiple strategies non degradable bioceramics/bioglass -encourage osseointegration -permanent biomat biodegradable bioceramic/ceramic composite -encourage bone ingrowth -balance deposition and degradation; tight control over degradation, pore structure, bone deposition, replaced by new bone

type II

nearly inert microporous mat, facilitating ingrowth of tissue -ingrowth of tissue into pores on surface or thruout implant, increase resistance to motion, decreases fibrous capsule, biological fixation -pores, must be at least 50 -150 um, capillary ingrowth, provide blood supply, larger to have bone ingrowth coatings to material addition of pores -decreases mech prop, porous ceramic coating norm to use bioact for coating

Raw materials/powder

obtain as powder raw materials -commonly precipitated in the lab/company -purifying mat precipitation -difficult process to control -large batches batch prop -primary particle size (TEM), size -> grain size -primary particle shape (affects packing), TEM, SEM, OVS -agglomerate size (particle size analysis) -agglomerate strength (affects packing) -phase purity (XRD), crystallinity, accurate within 5% -solute impurities care about chem of powder

cement line

only in secondary osteonal bone -result of remodeling process -form where osteoclast resorption ends and new formation begins -1-5 um thick -collagen I deficient structures pic lect 17

Routes

oral is E, all others are P

spherulite

polarized light microscopy light - amorphous

resorbable polymer

polyglycolic acid PGA -highly crystalline -high Tm -low solubility in organics -applications: absorbable suture, significant mech strength lost 2 -4 weeks, fast healing rate, internal bone fixation, biofix polylactic acid PLA -more hydrophobic than PGA -chiral molec; dexro and levo forms are not superimposable, different molec, utilize trait to control prop, pure d and l forms of PLA semicrystalline, mixed d and l forms amorphous, can affect mech prop adn degradation rates -applications: internal bone fixation, scaffold mat, L form -> polymeric stent -slow degrading polyglycolide lactide copolymer PLGA -adapt PGA to wider range of app -combine mroe hydrophobic PLA with PGA -PLA limit water uptake -redices rate of backbone hydrolysis -copolymer principle not fully applied, crystallinity of PGA rapid lost when copolymerized, why -> change in chem and structure; what prop will change -> decrease crystallinity and increase degradation rate; 50-50 copolymer degrades more rapidly than homopolymer because change in chem structure, change structure with chem -water -> decrease hydrolysis -PGA lose crystallinity -> density increase, greater chance water flow thru -applications: tissue eng, scaffold, drug delivery, surgical adhesive -hydriphibic degrade slower -crystalline help prevent degrade Polydioxanone PDO -high intial tensile strength -applications: ligament surger, stress shield, protects healing tendon grafts; tendons polycaprolactone -semicrystalline -low Tm 59-64 c -easily blended with other polymers -slower degradation than PLA -largely nontoxic and tissue compatible -applications: degradable staple, suture, tissue eng -incorp other bio, growth factor, tissue eng, proteins

super porous HA

remodeled why do authors want to use super porous HA -chem -lot of space for boen ingrowth advantages over normal level of porosity -bone ingrowth thruout, not just on surface -interconencted pores -bone deposition inside how was super porous achieved -dropping aqu phosphoric acid in suspension of Ca hydroxise -> HA slurry. slurry sprayed and dried -> spheroid powder, milled and mixed into soluble polymer soln. porosity and pore size controlled by bubbling in anionic surfactant. casted into mould. sintered. outcomes looking for -strength - compression -new bone deposition how was new bone formed within the pores -penetrate into superficial pores, 3D interconencted macropores and micropores, osteoblast did new bones fill all void space -no act diff in animals vs humans, good for young ppl not older, bone defects (filler) in what bme situations might this implant be ideal -no constant load, lower load situation -minor bone recosntruction (skull) -non weight bearing restrictions present? -metallic fixtures to help stabilize during intial bone growth choose longer time points, not numerous short time points

summary of engineering design

replacing bonem anatomic location -multiple strategies, type of injury -difficult to replicate bone structure/biology, determine how much is neessary to mimic -balance deposition, degradation, mech prop, architecture

type IV

resorbable mat, TCP -degrade gradually over a period of time, slowly, deposition of bone is a slow process, bone regeneration slower complications -maintenance of strength and stability during degeneration and replacement period -balancing degradation and repair rate, often desire near equal balance -mat must be made of metabolically acceptable material, ex TCP -body needs to be familiar with components

bme polymer: non resorbable copolymers

tetrafluoroethylene hexafluoropropylene FEP -high resistance to degradation -application sim to PTFE -melting point 265 C, easier to process, chem inertness and low friction -less energy to make flowable -tubing polyurethane - block copolymers -hard blocks, Tgs above room temp; diisocyanate and chain extender (2,4-toluene diisocyanate (TDI); methylene di(4-phenyl isocyanate (MDI)); chain extender (aliphatic glycol; diamine materials (2-6 Carbons)) -soft blocks, Tgs much lower than Trm; rubber characteristics, polyether polyols, MW 1000-2000, short chains -tough elastomers -good fatigue prop -applications: pacemaker lead insulation, vascualr graft, heart assist balloon pumps, artificial heart baldder -good fatigue prop -blood vessels, scaffold for heart musc

solid state sintering

use heat to densify mat solid sintering - thermally catalyzed densification -fire power at temp below Tm, enough energy to diffuse and move together -atomic and molec diffusion result in densification and loss of porosity, gets fused together neck together, merge into one particle initial step

methods to mimic structure

utilize preexisting cellular structures in nature -plant: wood, cellulose -coral complex porous structures use structures as a template how was wood used as a template -replacement strategy -> mult chem conversions to be repalced by mat we need

SiC modifications

what were outcomes of chem treatment -produce HA at surface could you use this in vivo -soak mat in SBF -a lot of questions about outcome disadvantages -reduction in porosity -a lot of effort, hard manu strategy you would use -diff species of wood -> more pores -nat strucutre already a ceramic -3D printed scaffold

SiC Ceramics

why cant we use SiC ceramics as is -no natural biocompatibility what do authors do to enhcance its funct -chem conversion to help promote bone regeneration and attachment of osteoblasts