BMEN 482 - Exam 2 Questions and Complete Solutions Graded A+

BMEN 482 - Exam 2 Questions and Complete Solutions Graded A+ What are stimuli responsive/shape memory polymers - Answer: Polymers that undergo a relatively large & abrupt physical or chemical change in response to small external changes in the environmental conditions Types of stimuli responsive polymers - Answer: Thermoresponsive, pH-responsive, glucose-responsive How do dual shape materials work? What stimulus can be used to enable recovery? - Answer: Dual shape polymers have a permanent structure (shape A) and a temporary shape (shape B). These materials can be programmed with a mechanical deformation that can be fixed (shape B). When an external stimulus is applied recovery occurs, where the polymer switches from its temporary shape back to its permanent shape. Stimulus includes: - Heat - light - electric field - magnetic field - immersion in water What is the process used to generate a secondary shape in thermally-induced shape memory polymers? - Answer: The primary shape A is heated above its transition temperature (either Tm or Tg) and is then deformed into the secondary shape B and is cooled. Material will hold this secondary shape B until it is heated above its transition temp again and will recover into its primary shape. How would you measure shape memory behaviour? - Answer: Strain fixity (Rf) T<Ttrans - Quantifies the ability of the materials switching segments to maintain/fix a mechanical deformation after cooling to result in a temporary deformation Strain recovery (Rr) T>Ttrans - Describes the ability of the material to memorize its permanent shape Rr and Rf should be 100% What is a netpoint? what is a switching segment? - Answer: Netpoints: Determine permanent shape, can be chemical covalent bonds or physical through intermolecular interactions. Stable at temperatures well above Ttrans Switching segments: exhibit a thermal transition (Ttrans = Tm or Tg). Relatively flexible above Ttrans, rigid below Ttrans What are the four types of molecular mechanisms responsible for shape memory polymer behavior? With examples? - Answer: 1. Physically crosslinked w/amorphous switching segments Ttrans = Tg Netpoints = crystalline domains Example: segmented polyurethanes 2. Physically crosslinked w/crystalline switching segments Ttrans = Tg Netpoints = crystalline domains Example: Segmented polyurethanes with PCL soft segments 3. Chemically crosslinked w/amorphous switching segments Ttrans = Tg Netpoints = chemical crosslinks Example: PMMA-PEGDMA networks, polyurethane foams 4. Chemically crosslinked w/crystalline switching segments Ttrans = Tm Netpoints: chemical crosslinks Example: PCL thermosets, ran-copoly-(ethylene/vinyl acetate) (EVA), PCL networks with hard & soft segments, networks formed from stearyl acrylate, MMA and BIS What happens to the Tg and why, when the PEG-DMA amount or MW is varied in PMMA-PEGDMA networks (chemically crosslinked w/amorphous switching segments)? - Answer: The Tg of PMMA is 105C and PEG is -41C. Due to PEGs much lower Tg when the amount of PEG-DMA is increased and its molecular weight is increased the Tg will decrease, as the segmental mobility of the chain will increase. Ways to increase the Tg of a copolymer network is to increase the molecular weight of the switching segment or to decrease the distance between the switching segments How are polyurethane foams formed? What are the reactive groups? What type of polymerization is it? What are the byproducts? How can you tune the Tg of the foams? - Answer: Polyurethane foams are formed with a condensation reaction between polyols (HPED) and diisocyanates (HDI). The reactive groups are the hydroxyl groups in the polyol and the isocyanate group in the diisocyanate. This forms a 100% amorphous thermoset network with a tunable Tg. The Tg can be tuned by increasing the hydrophilicity which will decrease the Tg or by increasing the crosslink density which will increase the Tg. Ways to increase the crosslink density include: - decrease macromer molecular weight - increase the number of functional groups on crosslinkers - increase macromer concentration What effect does varying the molecular weight of PCL/PDMS components in PCL networks with hard and soft segments have on the shape memory affect, Tg and Tm? - Answer: AcO-PCLn-PDMSm-PCLn-OAc PDMS - softening segment PCL - switching segments if n=5 and m=37 there is no shape memory effect if n=30 and m-37 there is a shape memory effect Ttrans = Tm Tm will increase with increasing Mn of PCL How can DSC be used to characterize shape memory polymers? How would the DSC curve differ as crosslink density increases or decreases? How would you increase or decrease the crosslinking density of an SMP? - Answer: DSC can characterize Ttrans, and crosslinking density (increased crosslink density raises Tg). Increase crosslink density by increasing the number of reactive groups on the crosslinker, decrease MW macromer or pendant crosslinkers, and increase macromer concentration What does the DSC curve from a block segmented copolymer differ from a random copolymer? - Answer: Block has two distinct Tgs for each block, random polymer has one generalized Tg How can DMA be used to understand the miscibility of polymer blends? How would the plots differ for miscible and immiscible homopolymers? - Answer: If the system is miscible the Tg of the resulting mixed system will sit in the middle of the parent Tg. If immiscible the blend will exhibit two different Tg that corresponds to that of the parent material. What is the main function of plasticizers? What happens to the Tg of a polymer after adding a plasticizer to its composition? Can you give an example of a plasticizer? What are plasticizers added to? - Answer: Plasticizers low MW materials that reduce intermolecular forces and are an additive that increase the plasticity/fluidity of a material by lowering/broadening its Tg. A common plasticizer is DEHP which is used in medical devices such as IV tubing, catheters, nasogastric tubes and dialysis bags. What is a hydrogel? What biomedical applications are they used in? - Answer: Hydrogels are lightly crosslinked water swollen polymer networks. They are used in wound dressings, skin tissue engineering and drug delivery What does physical and chemical crosslinking refer to? Explain the differences between natural and synthetic polymers, and the advantages synthetic polymers bring to biomaterial applications. - Answer: Physical crosslinking - thermoplastic hydrogels with non covalent crosslinks, stabilized by H-bonds and other secondary interactions Chemical crosslinked - thermosets, covalent crosslinks (cannot be melted) Natural polymer - typically proteins, bioactive/biological Synthetic polymers = PEG, silicone Advantages: controllable & reproducible chemistry/properties, can tailor molecular weight, block structures, degradable linkages and/or crosslinking methods What are some examples of natural polymers used in the clinic? Are they physically or chemically crosslinked? What are their applications? - Answer: Collagen: Physically crosslinked, stabilized by hydrogen bonds. Stays in solution at low pH & temp. Increase pH (neutral) and temp to body temperature polymer gels. Used in dermal fillers, injected in liquid form and then gels at body temp Alginate: physically (ionically) crosslinked. Negatively charged species in the backbone ionically interact with soluble cations to form 3D gels. Applications: dental impressions (powder with sodium alginate and calcium sulfate, crosslinks into a solid gel when mixed with water), cell delivery, tissue fillers. What are the advantages and disadvantages of using photoinitiators compared to thermal initiators when considering cell encapsulation and cytotoxicity? Can you give an example of new photoinitiators being developed? What are the advantages to these new photointiators compared to more commonly used initiators? - Answer: Thermal initiators (heat) - higher temp needed when compared to photoinitiators, reduced ability to encapsulate cells - can design to crosslink at body temp (cytocompatible & injectable), but take more time to gel and/or results in a lower crosslinking efficiency Photoinitiators (UV light) - Can conduct crosslinking at low temp - easy to control crosslinking - can crosslink through the skin, but with care to prevent burning - UV light is cytotoxic and can limit the encapsulation of cells New initiator: LAP - More cytocompatible - improved kinetics - longer wavelengths - cell encapsulation at lower concentrations - improved viability Can you identify hydrophilic monomers and crosslinkers? What type of polymerization reaction would be used to synthesize hydrogels? - Answer: Ester & amide groups Formed through additions reaction How can you alter crosslinking density in hydrogels? What would happen to crosslinking density if there are substantial amounts of interchain reactions? What affect does the increase or decrease of crosslink density have on the swelling ratio and modulus? - Answer: Decrease macromer MW, increase macromer concentration or increase amount of interchain reactions : increase crosslink density which will lead to: - decrease swelling ratio - increase modulus (stiffness) How is the swelling ratio measured? What properties does the swelling ratio of a hydrogel impact? - Answer: Swelling ratio = (Ws-Wd)/Wd * 100 Swelling ratio increases with decreased crosslinking density, polymer hydrophilicity, IPNs/Semi IPNs (different chain types repel each other and open up the network) Extent to swelling impacts hydrogel: - surface hydrophilicity - diffusion - optical properties - mechanical properties What is an IPN? How is an IPN synthesized? Can you give an example of an IPN? How does the properties of an IPN differ from a single network hydrogel? - Answer: An IPN is a combination of two polymer networks where at least 1 network is synthesized or crosslinked in the presence of the other. Crosslinked polymer is swollen in monomer solution which is then crosslinked into a second network At least 1 network must be hydrophilic Ig 1st network has a high crosslink density & the 2nd has a low crosslink density there is a double network hydrogel, which is very tough, ductile, strong, well-hydrated. Example: Asymmetrically crosslinked poly-(Am-co-AMPS) with poly-(Am) What is a semi-IPN? How is a semi-IPN synthesized? How does it differ from an IPN? - Answer: A semi-IPN is a chemical blend. A monomer is mixed with thermoplastic polymer and then the monomer is polymerized and crosslinked to form a network. There is no covalent bonding and the thermoplastic can be removed from the network. Often show superior swelling behaviors Can you give specific examples of no-degradable and biodegradable hydrogels? (2 from each category is fine). - Answer: Non-degradable: 1. Poly vinyl alcohol 2. Poly acrylic acid Biodegradable: 1. Co-polymers with polyglycolic acid and/or polylactic acid 2. Polypropylene fumarate How does the degradation rate of ester-containing hydrogels differ from amide-containing hydrogels? Why does the swelling ratio of ester-containing hydrogels change after implantation? - Answer: Ester-containing hydrogels degrade within the body, this leader to an increased swelling ratio over time due to decrease in the crosslink density. Esters are hydrolytically labile when switched with biostable amides there is no change in swelling ratio due to there being no degradation. What does LCST mean? What happens to the solubility of a polymer with an LCST when solution temperature increases or decreases? What is VPTT? What happens to the solubility of a Hydrogel with a VPTT when the solution temperature increases or decreases? What is the relationship between LCST and VPTT? - Answer: LCST: lower critical solubility temperature When temperature of a water soluble polymer with a LCST increases the polymer becomes insoluble as it decreases it becomes soluble. VPTT: Volume phase transition temp When temperature increases a hydrogel with a VPTT will deswell when the temperature decreases in will swell In general LCST 1-5C lower than VPTT What is the mechanism behind poly(NIPAAm)'s thermoresponsiveness and explain? - Answer: poly(NIPAAm) has a hydrophobic isopropyl group with a hydrogen bonding site. When the hydrogel is placed in water below the LCST it is soluble. Hydrogen bonding occurs between the amide group and water, water will surround the hydrophobic isopropyl group. When the water is above the LCST it will be insoluble and the H-binding is disrupted, there is reduced structured water around hydrophobic groups causing hydrophobic interactions to dominate as the isopropyl groups are pushed together. How could the thermosensitivity of hydrogels be improved? And how can you tailor the LCST? - Answer: Improve thermosensitivity: - introduce pores during fabrication - introduce hydrophilic moieties (reduce hydrophobic aggregation) - comb structure (graft poly(NIPAAm) faster shrinking) Tailor LCST - Hydrophilic monomers - increase LCST - Hydrophobic monomers - decrease LCST How would you modify the LCST of PEO-PPO-PEO block thermoplastics? What is the mechanism behind their swelling/compacting nature? What are the advantages of these block thermoplastics? What are their applications? Why are they described as amphiphiles? - Answer: LCST - 20-85C Increase length hydrophobic block (PPO) - decrease LCST More hydrophobic blocks - decrease LCST Increase concentration in water - decrease LCST Physically crosslinked hydrogel, crosslinks via reverse thermal gelation which is driven by hydrophobic interactions. Soluble in low temperatures heat above LCST insoluble and hydrophobic domains become physical crosslinks Advantages: viscous liquid @25C, gel at 37C, injectable, promote slow drug release Applications: Drug delivery Amphiphile: When a hydrophobic segment is coupled to a hydrophilic segment Can you give two examples of anionic hypercoiling polymers with carboxylic acid groups? (two examples are fine). - Answer: Poly(acrylic acid) (PAA), Poly(methacrylic acid) (PMAA) What happens to the polyacid at low pH? Is it coiled or uncoiled? What happens to a polyacid at high pH? Is it coiled or uncoiled? What is the mechanism which induces the coiling or uncoiling of a polyacid? - Answer: Polyacids contain an ionizable carboxylic acid group. At low pH, the group is uncharged and accepts protons making it act in a hypercoiled neutral state. At high pH, the group acts as a polyelectrolyte and donates protons making it act in a swollen charged state, due to electrostatic repulsion. As the size of the hydrophobic pendant group increases the polyacid will be even more compact at low pH What are Nanocomposite Hydrogels? What are the motivations to use them? How are nanostructures incorporated into hydrogels? - Answer: Nanocomposite hydrogel: a water-swollen crosslinked polymer network containing nanoparticles or nanostructures Motivation: improve mechanical properties, introduce stimuli-responsiveness, regulate swelling behavior Formation - Entrapped within the network, physical crosslinker, chemical crosslinker, absorb or attach to polymer chains What are three biomedical applications of polymer/silicates? - Answer: Smart drug delivery vehicles, wound dressings, lenses How are crosslinks formed in PEG/laponite? What structure does the laponite form when integrated into PEG? What does thixotropy mean? - Answer: Physically crosslinked via H-bonding, dipole, ionic and other interactions that attach polymer chains to laponite, reversible. Structure: house of cards structure Thixotropy: decrease in viscosity as stress over time increases. polymer adsorbs/desorbs with shear, injectable Application: self healing materials How is PNIPAAM/laponite crosslinked? How do the properties of PNIPAAm differ compared to when laponite is added? How can these properties be leveraged for cell culture? - Answer: Chemically crosslinked: NIPAAm polymerization initiated from laponite surface, KPS initiator, TEMED catalyst Increases toughness of Poly NIPAAm Used in cell cultures Culture cells in deswollen state (T>VPTT) Release sheet by cooling (T<VPTT) swelling-release If metallic nanoparticles demonstrate a weak association with a polymer what properties can be changed? - Answer: Unchanged properties: thermosensitivity, viscoelasticity Changed properties: electrical conductivity, response to optical stimuli, anti-microbial properties What biomedical applications can the hydrogels incorporating gold nanoparticles be used for? How does photothermal therapy work? What is the importance of the therapeutic window? - Answer: Drug carrier Photothermal therapy: Absorbs near-IR light, excites the gold, releases vibrational energy (heat), generated heat kills tumor cells Therapeutic window: Most biological tissues have relatively low light absorption in the visible & NIR spectral regions especially between 600-1300nm. NIR in therapeutic window can penetrate into tissue and be reflected back to the surface without being significantly absorbed by tissues. How does the incorporation of gold nanoparticles into PNIPAAM influence the polymers thermoresponsive behavior and electroconductivity? - Answer: Stronger covalent interaction with gold NPs Thermo-switchable electronic properties T<30C coil, T>30 globule Conductivity controlled average interparticle distance Swell - low conductivity Deswell - high conductivity What are the biomedical advantages of adding silver to a hydrogel? How are silver nanoparticles synthesized in-situ within the hydrogel/polymer? - Answer: Add electronic & anti-bacterial properties to hydrogel Polymer COOHs are temporary anchoring agent for attaching silver cation, the silver is then reduced to form NPs NP size more uniform if formed in a more highly crosslinked network How can the incorporation of magnetic nanoparticles influence drug release from PNIPPAAm hydrogels? - Answer: Fe3O4 responsive to magnetic fields Can be used as a remote controlled biomaterial to induce swelling/deswelling for drug delivery Magnetic field off - swollen, release off Magnetic field on - deswollen, release on Magnetic field off - swollen, release off Why do we care about the bulk and surface properties of polymeric biomaterials? - Answer: Bulk properties - thermal behavior, mechanical behavior, degradation. Influence the action of a material Surface properties - hydrophobicity, charge, physical characteristics. Surface properties are what the body see, they affect the biological response to implants and impact implant success What is surface tension? What is the difference between adsorption and absorption? - Answer: Surface tension: extra energy associated with a material surface due to unbound atoms with unfilled valance shells. Thermodynamically unstable therefore is the driving force of adsorption of proteins to material surface to minimize surface tension Adsorption - attachment/adhesion to a solid surface Absorption - penetration of molecules into the bulk of material Which surface properties affect protein adsorption? - Answer: Hydrophobicity, charge, physical characteristics How do you control the hydrophobicity/hydrophilicity of surfaces? - Answer: Synthetic polymers with methyl and styrene groups are hydrophobic The introduction of oxygen or nitrogen increases the hydrophilicity What effect does increased surface hydrophobicity have on protein adsorption? - Answer: Increased protein adsorption How does surface charge affect protein adsorption? - Answer: Occurs through the dissociation of ionizable surface groups or the specific adsorption of ions from solutions. The effect of surface charge depends on the charge of both the surface & protein What affect does increased steric hindrance and surface roughness have on protein adhesion? - Answer: Increased steric hinderance (PEG chains) decreased protein adsorption Increased roughness increased protein adsorption (trapped in valleys) Which factors contribute to the ideal surface modification technique? How can surface modification be accomplished? - Answer: Ideal surface modification: 1. Thin - minimizes effect on bulk 2. Resistant to delamination 3. Simple & robust 4. Discourages surface rearrangement Accomplished through: 1. post-fabrication processing 2. material synthesis How does plasma treatment work? What is plasma treatment often used for? What are the advantages and disadvantages of plasma treatment? (three advantages and three disadvantages) - Answer: Plasma is a molecularly dissociated gaseous environment with positive/negative ions, free radicals, electrons, molecules, and/or photons. You obtain plasma by applying an electric potential across a gas. The process for plasma treatment includes using a surface as a cathode which has a negative potential relative to the anode. Electrons travel from sample whole positive ions flow to the sample. Gaseous ions and radicals interact with sample and cause surface reactions. Free radicals polymerize molecules rom gas phase onto the surface or small molecules combine into larger particles that settle on the surface. Used for: cleaning, additions of -OH & -NH2 groups for further modification, direct polymerization of molecules to sample Advantages: free of voids, easily prepared, sterile when removed from reactor Disadvantages: expensive, chemistry within reactor ill defined, uniform reaction in long, narrow pores difficult What technique is used to apply solution coatings? what is the protocol for the technique? - Answer: Least complex surface modification Dip substrate into solution with dissolved coating material, dry substrate, coating is deposited on surface What are the primary concerns associated with biological surface modification? - Answer: The molecule must remain attached while maintaining bioactivity, orientation & rotational ability of individual molecules must be maintained so that conformation is not affected What are the advantages of biological surface modification using covalent attachment? - Answer: Increased stability What is needed for covalent attachment to occur? What are the advantages of using a spacer arm? Can you give the name of a common spacer? - Answer: Requires reactive substrate surface (-OH, -COOH, -NH2) A spacer arm is an inert molecule that provides physical space between the molecule & substrate Advantages: provide greater rotational freedom & improve bioactivity, can be designed to release biomolecule after implantation Example: Acrylate-PEG-NHS How is a biomolecule non-covalently attached to a surface? - Answer: Biomolecule is adsorbed to material by hydrophobic and/or electrostatic interactions What is the advantage of using knitted PET over woven PET for the formation of vascular grafts? - Answer: Knitted - fewer leaks - rigid/difficult to handle - in-growth new tissue prevented Woven - first infuse w/patients blood - more compliant Why is GORE-TEX (ePTFE) also used in vascular grafts? - Answer: Strong & microporous Which polymeric materials are used in a bileaflet tilting disk heart valve? What are the advantages of using a heart valve composed of these materials? - Answer: Pyrolytic carbon & Dacron or GORE-TEX sewing cuff. Advantages: biocompatible, thromboresistant, good durability, wear resistant, good strength What is the definition of hemocompatibility, hemostasis, and anticoagulation? How does thrombosis compromise device function? - Answer: Hemocompatibility: Material that does not cause thrombosis/clot formation. Does not change blood function/components Hemostasis: Mechanism to stop bleeding from injured vessels Anticoagulation: Medicine that helps prevent blood clots (heparin) Thrombosis can compromise device function by causing fatal embolism How does the hydrophobicity or hydrophilicity of a surface affect thrombus formation? - Answer: Hydrophilizing a surface can help with thromboresistance What approaches can be used to improve hemocompatibility? (be able to name 3 of the 6 approaches). - Answer: PEO/PEG coating, zwitterions, hydrogels What are the advantages of using silicon acrylates combined with MMA over PMMA to replace and intraocular lens? - Answer: PMMA: Tg 105C rigid, larger incision needed Silicones acrylates and MMA: foldable, lower Tg, smaller incision needed What are the benefits of using silicone hydrogels in soft contact lenses? which other biomedical application are silicone hydrogels used? - Answer: Advantages: Good O2 permeability Other applications: Wound dressings What is the difference between hard and soft tissues? - Answer: Hard tissues have becomes mineralized and/or have a firm intercellular substance How is bone tissue composed? What are the functions of osteoblasts, osteocytes, and osteoclasts? What is the function of the ECM? - Answer: Living Cells: - Osteoblasts: bone forming cells, produce collagen matrix & release calcium, magnesium & phosphate which form mineralized connective tissue - Osteocytes: osteoblasts become osteocytes when entrapped in matrix (maintenance) - Osteoclasts: bone absorbing cells, remove mineralized matrix ECM: A structural component of tissues that is not a part of the cells Includes: - Collagen fibers (type 1) - a fibrous structural protein - Carbonated hydroxyapatite - Proteoglycans - Water How does bone mineralization occur? What properties does mineralization impart on the collagen fibrils? - Answer: Bone mineralization: crystals (carbonated hydroxyapatite) of bone mineral form within & between collagen fibrils Aligned along collagen fibril axis to reinforce the collagen matrix & provide a very strong and tough composite What is the difference between cancellous and cortical bone? - Answer: Cancellous bone (spongy bone) - made up of individual trabeculae - elastic modulus 0.1-4.5 GPa - Porous/large surface area Cortical bone - 80% skeletal mass - elastic modulus 17-24 GPa - forms protective outer shell around bone - slow turnover rate - high resistance to bending & torsion - provides strength How does tensile strength and %elongation at break of the cortical bone in the femur change as a function of age? - Answer: Decreases What are the three types of cartilage? - Answer: Elastic (ear & nose), fibrocartilage (intervertebral space), articular (articulating ends of bones/joints) What is the function of chondroblasts and chondrocytes in articular cartilage? What is the composition of the ECM in articular cartilage? - Answer: Living cells: - Chondroblasts - precursors of chondrocytes - Chondrocytes - secretion & maintenance of matrix ECM: - Collagen fibers (type 2) 45% - tissue structure & tensile strength - Elastin fibers - Tissue structure & elasticity - Proteoglycans - resist compression, space fillers, provide hydrated space around cells - Water What is the definition of a long bone? Give an example of a long bone - Answer: Longer than they are wide Example: femur How does Wolff's Law of bone remodelling work? What is the goal of long bone treatment? What types of treatment are available? - Answer: Wolff's Law of remodeling - more stress applied, equilibrium shifted to osteogenic activity - less stress applied, equilibrium shifted to osteoclastic activity Goal: stabilize fracture (prevent motion between fragemetns) and allow remodeling Treatments: - nonsurgical: cast - surgical: external fracture fixation (fracture site not opened), internal fracture fixation (open fracture site) What properties should a bone plate exhibit? (be able to name 3). What is the function of a bone plate? - Answer: Properties: adequate stiffness & strength, no stress-relaxation or creep, non brittle behavior Function: restores continuity by compression of bone fragments (plate osteosynthesis). Affixed using screws. Used for places where casts can not be applied What is the problem with bone plates composed of metal? How does this issue lead to osteopenia? - Answer: Elastic modulus mismatch This leads to stress shielding and osteopenia (reduced bone mass) Result of removal of normal stress from the bone by implant as the metal fixation device carries too large a portion of the bones load. What polymer alternatives are there to metals for the construction of bone plates? - Answer: PEEK, CFR-PEEK, PPES, PES, PPS, PBPS What health issue is caused by articular cartilage damage? - Answer: osteoarthritis What polymer is used as the plastic spacer in knee replacements? - Answer: UHMWPE What are the two factors that lead to the failure of joint replacements? - Answer: Implant loosening - stress shielding (bone loss around implant) - wear debris How does the wear of UHMWPE acetabular cups lead to implant loosening? What is the process leading to implant loosening? - Answer: Wear particles migrate to bone and cause osteolysis This leads to rapid bone loss and implant loosening Immune response to wear particles Bone modeling balance upset - osteoclast activity increases - osteoblast activity decreases How can wear resistance be improved? - Answer: 1. Sterilization with gamma in an air-free environment leads to crosslinking What are the benefits of using CFR-PEEK as an alternative to UHMWPE for articulating joint replacement? - Answer: Higher wear resistance against CoCr, alumina, and zirconia surfaces compared to UHMWPE What are the definitions of bioactive, osteoconductive, and osteoinductive? - Answer: Bioactive: promoting integration/bonding with surrounding bone tissue and the attachment and differentiation of osteogenic cells Osteoconductive: permitting bone conformal growth onto a porous surface in order to guide the regeneration of bone in the desired shape Osteoinductive - Stimulating differentiation of multipotent cells into bone-forming lineages How is new bone produced at the interface of a bioactive implant and the bone? - Answer: 1. Ions leach out of bioactive implant and react with the ions in body fluids 2. Carbonated hydroxyapatite layer is formed between bone and implant 3. Osteoblasts migrate from existing bone into the HCA matrix 4. Osteoblasts differentiate, proliferate and generate new ECM 5. New bone is produced at the interface between the implant & bone What does biodegradation involve? What are the mechanisms of biodegradation? - Answer: Biodegradation: chemical scission/breaking of covalent bonds Mechanisms: hydrolytic, enzymatic, oxidative What bonds can be hydrolyzed? How is hydrolytic degradation catalyzed? What are the degradation products? Why doesn't PET exhibit significant degradation? - Answer: Hydrolysis: anhydrides & orthroesters > esters > amide > urethane > ethers (not significantly degradable) Water must be present, catalyzed by acid or base Degradation products are acids PET is a polyester that does not degrade, because of hydrophobic ring next to ester What is the difference between surface and bulk erosion? - Answer: Surface erosion: limited to the surface, a decrease of sample thickness with time rate(water penetration) < rate(hydrolysis) Hydrophobic polymers with very susceptible bonds Bulk erosion: erosion occurs throughout the entire volume, develops cracks/holes, breaks into pieces, pieces erode rate(water penetration) > rate(hydrolysis) Hydrophilic polymers with somewhat susceptible bonds Which polymers undergo bulk erosion? (name 3) - Answer: PGA, PLLA, PCL What factors contribute to different rates of hydrolysis? - Answer: 1. Increase hydrophilicity, increase rate 2. Decrease Tg, increase rate 3. Decrease crystallinity, increase rate 4. Increase temperature, increase rate 5. Acid or base present, increase rate 6. Increase porosity/surface area, increase rate What is the motivation in using polymers for improved drug delivery? - Answer: Maximize drug activity, minimize side effects, deliver low MW drugs with poor water solubility/poor tissue penetration What is the traditional role of a polymer drug excipient? - Answer: Inactive carrier for active ingredients. Tablets/capsules. Binder, coating or anti-adherent. How does immediate release of drugs occur? - Answer: Polymer disintegrates, the drug released (in minutes) into the stomach (drug must be stable in acidic pH), moves into the small intestine, systemic circulation How are polymers used in immediate release dosage forms? What polymers are used in each type of form? (be able to name 2). - Answer: Tablets: - Binder for compacting drugs, holds together - anti-adherent, prevent drugs from sticking to each other - coating, preventing disintegration, mask taste, color code, aesthetics & safety Examples: PNVP & PEG Capsules: an alternative to tablets for poorly compressible drugs - polymer excipient, inactive carrier for 1 or 2 pieces of drug Examples: Gelatin, PNVP How do delayed-release dosage forms work? What type of drugs are they used for? - Answer: Release into the small intestine directly, puts more drugs into the systemic circulation Good for drugs not stable in an acidic environment What mechanisms are used for the spatial control of drug delivery? How does an enteric coating work? - Answer: 1. Surgically implant drug delivery system directly at the site Polymer holds drug at sire and is then released 2. Use a targeting mechanism The polymer acts as a carrier and gets the drug to the desired site where it is released Enteric coating The coating is applied to the drug to control where it is absorbed, and prevent the release of medication before it reaches the small intestine Can be pH-sensitive polymers What is the difference in sustained drug release and pulsatile controlled release for temporal drug control? - Answer: Sustained release - occurs via diffusion/degradation - therapeutic drug level sustained over a long period of time - good for rapidly metabolized drugs Pulsatile controlled release - occurs via swelling/deswelling - at therapeutic drug level only when necessary - good to minimize effects How does sustained release of drugs occur at the macroscopic and molecular level? - Answer: Macroscopic: drug passes through pores Molecular level: drug passes through polymer chains What is the difference between matrix and reservoir diffusion? - Answer: Matrix diffusion: polymer and drug mixed to form a homogenous system. Over time release rate decreases as the drug has a longer distance to travel to the external environment Reservoir diffusion: drug reservoir in a matrix surrounded by a film that controls release. The drug delivery rate remains fairly constant How does swelling and de-swelling controlled release work? - Answer: Ideally no diffusion until swelling (or deswelling) event and diffusion at desirable levels during swelling (or deswelling) on-off control through stimuli responsive hydrogels Matrix: matrix shells Reservoir: membrane film swells What is the advantage of using hydrogels for drug delivery? How can matrix and reservoir systems be prepared? What mechanisms can be used for controlled drug delivery? What stimuli can the hydrogels be made responsive to? - Answer: Hydrogels advantages: high biocompatibility, high water content and soft surface properties, adsorption proteins are minimized, increased circulation time Matrix: drug uniformly distributed in highly crosslinked hydrogels Reservoir: drug/hydrogel core covered with a water-insoluble membrane Mechanism Diffusion: delivery at controlled rates (non-responsive) Swelling/deswelling: pulsatile/on-off control (stimuli-responsive) Examples: temperature, pH, glucose How are pluronics (PEO-PPO-PEO) used in sustained drug release? - Answer: Slow drug release via diffusion through gel, improves peptide stability, paclitaxel injected intratumorally delayed tumor growth, lidocaine injected near sciatic nerve prolonged drug release How can non-degradable polymers be used for sustained drug release? (be able to name 2 types of polymers for sustained release that degrade by bulk and surface erosion) - Answer: Sustained release over long periods of time Rate of diffusion controls drug release 1. PDMS: birth control like Norplant 2. Thermoplastic PDMS: intraocular drug delivery 3. Transepidermal patch: smokers, Parkinson's, contraception Polymers used: PVC, PS, PU, PVAc Bulk erosion: PGA, PLAs Surface erosion: polyorthoesters (gentamycin), polyanhydrides (antineoplastic) How are biodegradable microparticles used to deliver drugs? Can you name a specific application? - Answer: Useful for oral and injected drug delivery PLGA microparticles are widely studied Luteinizing hormone-releasing hormone used for the treatment of hormone-dependent cancers 3microm inhalation <1nm for injection <100nm to be taken up by the cell What are the 5 different types of microparticle formulations? - Answer: 1. Microcapsule with a solid core 2. Microcapsule with non-solid core 3. Microcapsule with solid micro/nanodomains 4. Microcapsule with non-solid micro/nanodomains 5. Microsphere with a molecular mix of matrix & drugs How can hydrophobic drugs be delivered using microparticles? - Answer: Easier to formulate in slowly degrading microparticle systems If water solubility too low, release may be too slow, use porous microparticles Taxol: cancer drug: solid tumors breast/lung water insoluble so requires formulation with poluoxytheylated castor oil for injections, serious hypersensitivity Use PLGA microparticles (30microm) In vitro: slow sustained release Taxol w/no initial burst Added pores: channels for diffusion