bme 3170: exam 1

Describe the difference between a normal wound response and an implant response

• normal wound response: involves tissue injury, inflammation, tissue removal, and tissue remodeling —> scar tissue

• implant response: involves tissue injury, inflammation, tissue removal, chronic phase —> fibrous capsule

what is a fibrous capsule

• tough, protective layer of connective tissue that encases organs, joints, or foreign medical implant

• part of body’s response to “walling-off” implant

what is the chronic phase in implant wound healing

• prolonged inflammatory and tissue remodeling stage characterized by the foreign body reaction that leads to formation of fibrous capsule

explain the proliferative phase and the remodeling phase of wound healing

• proliferative phase:

  • initiated by monocytes and macrophages within 1 day on implantation

  • 3-5 days: fibroblasts and vascular endothelial cells proliferate to form granulation tissue

  • fibroblasts synthesize collagen which leads to fibrous capsule formation

• remodeling phase:

  • occurs immediately after granulation tissue is laid down

  • formation of scar tissue (aligned collagen tissue)

  • requires degradation of granulation tissue by collagenase (released by inflammatory and other extracellular matrix cells) alongside deposition of collagen fibrils

  • degree and properties of remodeling tissue vary depending on tissue type

what is a fibroblast

• most common type of cell found in connective tissue thats in charge of synthesizing structural framework (extracellular matrix and collagen) of tissues

what is the extracellular matrix

• non-cellular web of proteins and carbohydrates that surrounds, supports, and gives structure to cells within tissues

what is a monocyte

• a white blood cell that act as a mobile reserve, monitoring the body for signs of infection or tissue damage

• circulating precursors in blood

what is a macrophage

• a differentiated monocyte (once it enters a tissue) that are long-lived cells that permanently reside in tissues or migrate to sites of injury

• mature, active cells in tissues

list some of the proteins that are absorbed on the surface of an implanted material

• albumin

• IgG

• fibrinogen: ready absorbs, denatures, and exposes hidden epitopes that lead to neutrophil and macrophage accumulation

list some of parameters that control the foreign body reaction

• surface properties of biomaterial

• form of the implant

• surface to volume ratio of the implant

• topography/roughness of the implanted material (ex: rough vs smooth surfaces)

describe the process of fibrosis

• fibrosis: the formation of a thin layer of soft tissue (fibrous capsule) that covers an implant to isolate it from body

  • repair at implant site:

    • replacement of injured tissue by the same cell type

    • fibrous capsule formation

  • permanent cells (nerve, cardiac, skeletal) lead to fibrous tissue formation

  • stable or mesenchymal cells lead to fibrous encapsulation because implant hinders normal regeneration

what are stable cells

• cells that do not multiply but retain ability to divide rapidly in response to injury

what are mesenchymal cells

• multipotent stem cells that can differentiate into a wide variety of connective tissues

define frustrated phagocytosis

• process that occurs when a phagocyte attempts to engulf a target that is too large for it to fully consumed

  • phagocyte increases contact with the target surface → spreading too thin → lamella shaped cell that partially covers the target → recruits more phagocytes → releases enzymes (phagocytic oxidation) to degrade the biomaterial

list the classic signs of inflammation

• redness (increased concentration of red blood cells)

• heat

• pain

• swelling (increased pressure on pain receptors

list the three reactions the body has to a foreign body

• expel: fight off

• wall off: blocks

• ingest: takes in

explain the host response and the material response

• host response: biological reaction of body to implanted material

  • includes: inflammation, cellular invasion, immune system activation, tissue remodeling, foreign body reaction, fibrous capsule formation

• material response: behavior and changes of the implant material in response to the physiological environment

  • includes: protein adsorption onto its surface, degradation/corrosion from cellular attack or phagocytic enzyme release, and physical/chemical interaction with surrounding tissues

what is a crystal

• a solid material where atoms self organize in a periodic array

  • single crystal: atoms are in a repeating or periodic array over the entire extent of the material

  • polycrystalline material: comprised of many small crystals or grains

what are the three crystal structures

• body centered cubic: atom sits at each of the eight corners of a cube and one atom sits directly in center

• face centered cubic: atoms located at eight of the eight cube corners and the center of all six faces

• hexagonal closed packed: hexagonal prism three layers within a single repeating unit cell

  • top and bottom layers (A layers): one atom at each of six corners and one atom in face center of top and bottom layer

  • middle layer (B layer): three full atoms sit entirely inside the unit cell

explain the different classes of materials

• metals: held together by non-directional (isotropic) metallic bonds where metal atoms have free valence electrons that can travel about the material

  • pure metal elements or alloys

  • high electrical and thermal conductivity and allow plastic deformation

• ceramics: inorganic compounds composed of combinations of metallic and non-metallic atoms bound by ionic or covalent bonds

  • more open, complex crystal structures

  • bound electrons limits thermal/electrical conductivity and ionically bonded ceramics are brittle

• polymers: composed of carbon atoms bound together by highly directional covalent bonds

  • built from a basic repeating unit (mer) forming linear, chainlike structures

  • categorized as either thermoplastic or thermosetting

what does it mean to be thermoplastic

• can be melted and reshaped repeatedly

what does it mean to be thermosetting

• harden permanently after being heated once

what is plastic deformation

• permanent change in shape or size of a solid material that occurs when it is stressed beyong its elastic limit

explain the uniqueness of carbon

• listed under ceramics as an inorganic material yet seves as foundational atomic backbone for polymers

• exhibits polymorphism, existing as distinct crystal structures with identical composition

what is polymorphism

• ability to freeze into different crystal structures despite having the exact same chemical identity

explain viscoelasticity

• mechanical behavior of materials that combines viscous flow and elastic response, associated with time dependent phenomena such as creep

• “silly putting effect”

what is creep

• slow, permanent, and progressive deformation of a solid material that occurs overtime when subjected to prolonged mechanical stress

  • accelerated by time and high temperatures

explain the function and give examples of collagen rich and elastin rich tissues

• collagen rich: to withstand tensile (pulling) loading

  • ex: tendons, ligaments, cartilage

• elastin rich: provide flexibility and withstand tensile loading in structures subject to repeated bending or expansion

  • ex: blood vessels, skeletal muscle, elastic cartilage

explain the stress strain relationship of load bearing connective tissue

• general shape: non-linear, strain-rate dependent, and characterized by energy loss (hysteresis)

• toe region: initial non-linear region where crimped collagen fibers uncrimip and align in direction of load

• linear region: where aligned fibers are stretched along their axes, providing maximum stiffness

• yield/failure region: where individual fibers begin to micro-rupture before complete failure

explain why ligaments are less strong/less stiff than tendons

• ligaments: contain lower collagen density and higher matrix content, more woven fiber arrangement, slightly higher elastin content

• tendons: have highly parallel, uniaxial fibers, not as much elastin

explain the effects of creep and stress relaxation on tendons and ligaments

• creep on tendon: slightly lengthens under constant stress, letting muscle contract further to recruit more fibers and reduce fatigue

• relaxation on tendon: internal stress decreased over time under constant strain

• benefit: allow joint structures to loosen slightly over time under sustained load, reducing potential injury risks

creep in viscoelastic materials

• time dependent increase in strain/deformation when under constant stress

stress relaxation in viscoelastic materials

• time dependent decrease in stress when held at constant strain/length

rate dependency in viscoelastic materials

• stiffness and strength increase when material is loaded at higher strain rates

what is hysteresis

• energy dissipated (lost as heat) during a cycle of laoding and unloading

explain Wolff’s Law

• living bone adapts its structure (remodels) in response to mechanical loads placed upon it

  • high mechanical strains trigger new bone formation

  • reduced loading triggers osteoclasts to break down bone

  • internal spongy bone re-orient along principal stress trajectories to maximize strength

  • bone mass shifts toward concave side of bending force to minimize flexural deformity

  • optimizes bone’s strength to weight ratio by adding material only where needed

describe why type 316L stainless steel is not recommended for long-term use as fracture plates

• corrodes in highly stressed and oxygen-depleted regions (ex: contact areas under screws of fracture plate)

explain what fabrication method should be used to make the 316L stainless steel fracture plates are why

• cold-working is used because strain hardening through mechanical deformation at normal temperatures increases strength and hardness

explain the difference between wrought and cast Co-based alloys

• cast alloys: formed via investment casting (lost wax process)

• wrought alloys: mechanically worked (cold or hot) for superior tensile and fatigue strength

what is investment casting

• coating a wax replica of a part in ceramic, melting the wax out to leave hollow mold, and filling old with molten metal to create final part

what is cold working

• mechanically shaping metal at room temp, distorting internal crystal grains and permanently strengthens material through strain hardening

what is hot working

• shaping metal at high temperatures above its recrystallization threshold, allowing new. stress-free grains to continuously form so metal remains highly malleable without cracking

list the three microstructural defects that might occur with cast Co-based alloys

• cored microstructure: resulting from dendrites- chemical imbalance where high-melting point cobalt locks into branch centers and shoves elements to outer edges

• dendrite formation: tree-like crystal branches as molten cobalt alloy sodifies

• large grain sizes

explain the function of Cr, Ni, and Mo additions to 316L stainless steel

• Cr: imparts corrosion resistance and stabilizes ferritic phase

  • ferritic phase: magnetic, room temperature form

• Ni: stabilizes austenitic phase and enhances corrosion resistance

  • austenitic phase: non-magnetic, high temperature form that gives steel toughness and corrosion resistance

• Mo: enhances resistance to pitting corrosion

describe why reducing carbon content from 0.08% to 0.03% improved the mechanical and chemical properties

• improves corrosion resistance

why is Ti and Ti alloys less desirable for bone screws and fracture plates

• poor shear strength despite having excellent strength per density

what is the purpose of aluminum and vanadium in the Ti alloy

• aluminum: stabilizes alpha phase

  • alpha phase: stable, room temp form of Ti arranged in NCP that provides strength and creep resistance

• vanadium: stabilizes beta phase

  • beta phase: high temp form of Ti arranged in BCC that makes metal highly formable and easily heat tratable

what are the passivation layers for the following: stainless steel, Cr alloys, Ti alloys

• stainless steel: forms surface chromium oxide (Cr2O2)

• Cr alloys: forms chromium oxide layer

• Ti alloys: forms titanium dioxide layer (TiO2)

what is a passivation layer

• self-healing oxide film that spontaneously forms on surface of certain metals to block oxygen and moisture

explain why wrought CoNiCrMo alloy is one of the strongest implant materials available

• combines cold worked matrix phase, solid solution strengthening, and precipitation hardening

list the interstitial elements that can be added to titanium

• oxygen

• carbon

• nitrogen

explain why interstitial element might be added to titanium

• strengthen material through interstitial solid solution strengthening mechanisms (ex: oxygen increases yield strength)

explain what 45S5 means

• formula containing 45 wt % silica (SiO2) with a 5:1 of CaO to P2O5

list the three key features of a bioglass that distinguishes it from regular plate glass

• less than 60 mol % SiO2

• high Na2O and CaO content

• high CaO/P2O5 ratio

describe how does a bioglass form a bond with bone

• forms a biologically action carbonated hydroxyapatite (HA) layer simultaneously with CaO, P2O5, and SiO2 rich layer on reactive surface

explain what is partially stabilized zirconia

• zirconia stablized with additives (ex: 6 wt % yttria (Y2O3)) to maintain high temp cubic/tetragonal phase and resist phase-transformation volume changes

list the desirable properties of bioglass/glass ceramics

• low thermal coefficient of expansion

• good tensile strength

• high resistance to scratching and abrasion

list the undesirable properties of bioglass/glass ceramics

• brittleness (low fracture toughness)

explain how bone is attached to CaP (note bonding to none is different for CaP than bioactive glasses)

• attaches through the growth of an epitaxial bonding layer

list the factors that increase biodegradation of CaP ceramics

• increased surface area

• decreased crystallinity, crystal perfection, or grain size

• ionic substitutions of CO3(2-), Mg(2+), and Sr(2+)

list factors that decrease biodegradation of CaP ceramics

• fluoride (F(-)) substitution

describe the four ways of attaching ceramic prostheses to the skeletal system

• morphological fixation: dense, nearly inert ceramics into surface irregularities

• biological fixation: bone ingrowth into porous ceramics

• bioactive fixation: chemical bonding at surface reactive ceramic interface

• resorbable replacement: slow replacement by natural bone tissue

describe the addition reaction (include the three steps) and give an example

1. initiation: free radical activation

2. propagation: rapid monomer addition

3. termination: joining of radials

• ex: polymerization of polyethylene from ethylene monomers

describe the condensation reaction and give an example

• step growth reaction where functional groups combine to form long polymer chains, producing a small molecule byproduct at each step

• ex: synthesis of nylon (polyamide)

describe what happens to chain mobility as the chains increase and how it is related to mechanical strength and molecular weight

• as chain length and MW increases, entanglements increase —> restricts chain mobility —> increased mechanical strength and viscosity

explain the importance of crystallinity as it pertains to mechanical properties

• higher crystallinity increased packing density and intermolecular bonding

  • higher tensile strength, modulus, and hardness

  • reduced ductility and impact resistance

explain the term polydispersity

• the range of different chain lengths or particle sizes in a polymer or particle sample

• the measure of the breadth of the molecular weight distribution in a polymer sample

• defined by ratio of weight-average to number-average molecular weight

• PDI = (Mw/Mn)

describe how PVC can be made flexible and why it isn’t recommended for long-term use

• made flexible by adding low-molecular-weight plasticizers

• unsuitable because plasticizers leach out over time, causing embrittlement and potential toxicity

what are plasticizers

• chemical additives mixed into polymers to increase flexibility, stretchiness, and workability by reducing friction between molecular chains

explain why some polymers readily crystallize and other polymers do not

• readily crystallize: simple structures, high symmetry, stereoregularity, and strong interchain forces

• prevent crystallize: bulky side chains or random structures

explain why polypropylene’s crystallinity rarely exceeds 50-70%

• methyl side groups introduce steric hinderance and structural defects during chain folding, leaving amorphous regions trapped between crystalline lamellae

explain why nylon has excellent fiber forming ability

• regular amide groups along backbone form strong, extensive interchain hydrogen bonds, allowing high chain orientation upon drawing

list advantages of bioerodible materials

• eliminate need for surgical removal after healing

• prevent chronic FBR

• allow gradual load transfer to repairing tissue

• enable controlled release of encapsulated drugs

list some of factors influencing the bioerosion rate

• chemical bond stability

• hydrophilicity/hydrophobicity

• crystallinity

• molecular weight

• porosity

• surface to volume ratio

• local mechanical stress or pH

list some of the requirements in terms of biocompatibility of degradable polymers

• non-toxic polymer and degradation byproducts

• non-immunogenic/inflammatory reaction

• clearance or metabolism of degradation products without systemic accumulation

explain zero order release

• drug release that occurs at a constant rate over time

explain the therapeutic index

• safe drug concentration range located between minimum effective level and toxic level

describe the burst effect and why does it occur

• initial rapid release of large amount of drug, caused by drug accumulation at or near the device surfacing dissolving quickly upon exposure

explain the diffusion controlled delivery systems-monolithic and membrane control

• monolithic diffusion controlled: drug dispersed/dissolved within a polymer matrix

• membrane diffusion controlled: feature a drug core surrounded by a rate controlling polymer membrane

explain what the rate limiting step is for a membrane controlled delivery system and why it is important for the flux to remain constant

• drug diffusion across membrane

• flux must be constant to ensure zero-order release

  • done by maintaining unchanged membrane properties and constant change in C

explain water penetration controlled delivery systems

• delivery rate is governed by water volume flux

  • osmotically controlled devices and swelling controlled devices

what is a osmotically controlled device

• water drives a movable partition to force drug out

what is a swelling-controlled device

water swells a polymer, shifting Tg below ambient temperature to release drug