Outline

1
Polymeric Biomaterials For Orthopedics

• Outline
• Bone and Bone Tissue
• Cartilage Tissue
• Orthopedic Fracture Fixation
• biostable polymers
• Total Joint Replacement
• non-degradable polymers
• Orthopedic Fracture Fixation, etc
• - biodegradable polymers

2
Tissues
Biomaterial a material that can function as a
whole or part of a device to treat, assist,
repair or replace an tissue, organ, or function
of the body.
Tissue Define Organ Define
3

• Types of Tissues
• 1. Epithelial tissue
• covers the body surface and forms the lining for
  most internal cavities
• the skin is an organ made up of epithelial tissue
• Function protect
• Connective tissue
• Most abundant
• ___________, ____________blood, tendons,
  ligaments
• Function _______________, ______________, binds
  tissues together
• 3. Muscle Tissue
• Skeletal contraction of skeletal parts attached
  to bone via tendons
• Smooth walls of internal organs and blood
  vessels
• Cardiac walls of the heart
• Nerve Tissue
• Consists of nerve cell or neurons located in the
  brain, spinal cord, and nerves
• Produces and conducts nervous impulses to and
  from all parts of the body.

4
Bone Tissue vs. Bone

• Tissue
• Bone or Osseous Tissue
• ? A Connective Tissue
• mineralized connective tissue
• ? A Hard Tissue (see next slide)
• tissue that has become ____________________
• tissue having a __________________________________
  ___
• Cartilage is also a hard tissue but it is not
  mineralized
• Organ
• Bone
• 1. Rigid organ primarily composed of
  ____________________

5
HARD TISSUES VS. SOFT TISSUES
Connective Tissues Connect, support, or surround
other structures and organs of the body

• Soft Tissues
• Muscles support/moves bone
• Tendons connect muscles to bone
• Ligaments connect bone to bone
• Synovial tissue makes up joint capsule
• Fascia sheet or band of fibrous connective
  tissue enveloping, separating, or binding
  together muscles, organs, and other soft
  structures of the body.
• Also nerves, blood vessels, fat
• Hard Tissues
• Tissues that have become mineralized /or have a
  firm intercellular substance
• Cartilage and bone

6

• Bone tissue is different from bones
• bones are __________ made up of bone tissue as
  well as marrow, blood vessels, epithelium and
  nerves
• bone tissue refers to the _______________________
  ___that forms the rigid sections of the organ.

7

• Two Major Types of Bone Tissue
• 1. Cancellous bone (or trabecular bone /
  spongy bone)
• - made up of individual trabeculae
• - Elastic Modulus ______________
• 2. Cortical bone (or compact bone)
• represents nearly 80 of the skeletal mass
• Elastic Modulus ________________

Steak T-Bone
Human Pelvis
depts.washington.edu/bonebio/bonAbout/trab1.jpg
8
BONE TISSUE COMPOSITION

• Living cells
• - osteoblasts __________________ produce
  mineralized collagen matrix
• - osteocytes osteoblasts become osteocyctes
  when entrapped in matrix
  (maintenance)
• - osteoclasts _____________________ remove
  mineralized matrix (bone
  resorption)
• osteoblasts
• deposit a matrix of collagen and release
  calcium, magnesium, and phosphate ions, which
  chemically combine and harden within the matrix
  into _____________________________mineralized
  connective tissue.

9
BONE TISSUE COMPOSITION

• Extracellular Matrix (ECM)
• A structural component of tissues that is
  _______________________.
• - collagen fibers (Type I) - a
  fibrous structural protein
• - 25
• - carbonated hydroxyapatite
• - proteoglycans
• - water 20

FYI - Proteoglycans composed of a protein
backbone to which is attached long side chains of
negatively charged glycosaminoglycan (GAGs)-
long, unbranched polysaccharide units e.g. GAGs
hyaluronan, chondroitin sulfate, keratan sulfate,
heparin, etc
10
COLLAGEN

• Main component of bone tissue and cartilage
  (also, skin, teeth, ligaments, etc)
• ________________make up the extracellular matrix
  (ECM) to support cells
• A fibrous structural protein
• Provides structure and strength to bone tissue
  and cartilage
• STRUCTURE
• Primary Structure Amino Acid Sequence

Gly 1/3 or 33 X usually Pro 13 Y usually
Hyp 10 or X and Y other amino acids
Note you should know formula, s, amino acid
names (but not structures of amino acids).
Glycine (Gly)
Proline (Pro)
Hydroxyproline (Hyp)
11
COLLAGEN STRUCTURE
_________________________________ - right handed
triple helix of - 3 polypeptide strands (MW
100K) - strands held together by H-bonding -
total MW 300K - Rod is 300 nm long and 1.5 nm
diam. Tropocollagen undergoes self-assembly to
form ______________(10-300 nm diam.) (see next
slide for 3-D detail) Assembly results in a
____________ _________________________which
are staggered by 1/4 length of
individual molecule
fibril
tropocollagen
fibril
Staggered tropocollagen
Fibril stabilized by crosslinks
12
Organization is 3-dimensional
fibril
Collagen fibers (2 ?m)
13
BONE TISSUE FORMATION
During fibril formation
Crystals of bone mineral form within and between
collagen fibrils in a process called bone
mineralization. The crystals are The crystals
are aligned along the axis of the collagen
fibrils and reinforce the collagen matrix to
provide a very strong and tough composite.
14
http//www.soe.uoguelph.ca/webfiles/kgordon/Academ
ic20Courses/Bone_for_Biomaterials.htm

• Cancellous bone
• made up of individual trabeculae, each with it's
  own stiffness, that form a
• structure that has it's own unique stiffness.
• Therefore cancellous bone has a material
  stiffness, which is the stiffness of
• each trabecula, and a structural stiffness
  which is the stiffness of the trabecular
• structure.
• Cortical (compact) bone
• represents nearly 80 of the skeletal mass
• it forms a protective outer shell around every
  bone in the body.
• It has a slow turnover rate and a high
  resistance to bending and torsion.
• It provides strength where bending would be
  undesirable as in the middle of long
• bones.

15
BIOMECHANICS OF BONE ANISOTROPIC BEHAVIOR
ANISOTROPICStrength of bone depends on (a)
whether it is loaded in ___________________and/or
(b) if the load is supplied ______________________
_____to the bone The difference is due to the
relative orientation of the osteons to the
applied load (a) Cortical bone is stronger in
compression than in tension. StrenthCompression
Strengthtension In compression EL
3 -regardless if load is longitudinal or
transversely applied.
x
x
Stressstrain plot for human cortical bone for
tensile and compressive loading. Data are shown
for a longitudinal loading direction.
16
BIOMECHANICS OF BONE ANISOTROPIC BEHAVIOR
(b) If cortical bone is loaded transversely in
tension (rather than longitudinally in tension),
the strength (E, T.S.) and elongation at break
(i.e. strain to failure) is reduced substantially.
x
Stress
Stress
x
Strain
17
BONE TISSUE MECHANICAL PROPERTIES
Tensile Strength (MPa) and elongation at break
of cortical bone from the human femur as a
function of age
Healthy bone
Osteoporosis
Bone tissue is stronger in compression vs. in
tension _______________
18
CARTILAGE

• hard connective tissue
• 3 Types of Cartilage in Human Body
• (1) _________________________
• -ear and nose
• (2) ___________________ - Intervertebral space,
  meniscus, TMJ
• (3) _________________________
• - articulating ends of bones
• - protects underlying bone in a joint from
  abrasion and wear
• - if damaged (trauma, osteoarthritis), bone
  is exposed to stress
• concentrations leads to pain from
• the nerves in the bone

19
ARTICULAR CARTILAGE COMPOSITION

• Living cells
• - _______________ precursors of chondrocytes
• - _______________ secretion and maintenance of
  matrix
• (2) Extracellular Matrix
• - Collagen fibers (Type II) Tissue structure
  and tensile strength 45
• - Elastin fibers (structural protein) Tissue
  structure and elasticity
• - Proteoglycans
• - resist compression
• - serve as space-filers
• - provide hydrate space around cells
• - Structure composed of a protein b.b. to which
  is attached long side chains of negatively
  charged glycosaminoglycan (GAGs)- long,
  unbranched polysaccharide units
• - GAGs hyaluronan, chondroitin sulfate, keratan
  sulfate, heparin, etc
• - Water 70

20
Hyaluronan (a GAG)
Structure of the ECM
21
Bone Tissue vs. Cartilage Water Content
22
Bone Tissue vs. Cartilage Collagen Content
23
Bone Tissue vs. Cartilage Mechanical Properties
24
LONG BONE REPAIR

• Long bones
• Are longer than they are wide
• Ends covered with _____________________
• Ex. femurs, tibias, fibulas (leg) humeri,
  radii, ulnas (arm) phalanges and toes

25
LONG BONE REPAIR

• Bone tissue undergoes spontaneous regeneration
  and remodeling
• Accomplished via balance between
• Wolffs Law of Bone Remodeling
• - More stress applied ? equilibrium shifted to
  ___________ activity
• - Less stress applied ? equilibrium shifted to
  ____________ activity
• Goal of long bone fracture treatment
• - stabilize fracture (prevent excessive motion
  between bone fragments) and allow bone
  regeneration/remodeling

Could better biomaterials allow this to occur
better?
26
LONG BONE REPAIR

• Types of Treatments
• Non-surgical cast
• 2. Surgical
• a. external fracture fixation
• - do not open fracture site
• - bone fragments held together by pins through
  
• skin onto skeleton and structurally
  supported
• by external bars.
• b. internal fracture fixation
• - open fracture site
• - bone fragments held together by wires,
• screws, plates, and /or intramedullary
  devices

EXTERNAL FIXATION DEVICES
27
INTERNAL FIXATION DEVICES
Bone Plates
Intramedullary Nails/Rods
Pins
Screws
28
PLATES
Gross slide next.
29
BONE PLATES

• Bone plates are affixed using screws on to the
  bone over the fracture
• Used for
• 1. Places where casts can not be applied to the
  injured area
• -- facial areas such the nose, jaw or eye
  sockets
• 2. Femural fractures
• 3. Other fractures
• referred to as ______________________

30
PROPERTIES REQUIRED FOR BONE PLATES

• A fractured bone has lost its support function
  due to discontinuity (break).
• A bone plate ______________________ by
  compression of the bone fragments.
• Bone plate materials should exhibit
• 1. Adequate modulus of elasticity (E)
• - stiffness should be close to that of bone
• 2. Adequate strength (tensile, compression,
  flexural, etc).
• 3. No stress-relaxation or creep dimensionally
  stable
• 4. Non-brittle behavior some toughness,
  ductility (adapt to curved
• bone surface)
• 5. Required mechanical properties during entire
  healing period
• 6. Biocompatible

31
METALLIC BIOMATERIALS FOR INTERNAL FIXATION
DEVICES
Wong and Bronzino, 9-6.
32
CONVENTIONAL METALS FOR FIXATION

• Stainless steel 316L
• - ASTM F138, F139
• - Iron (60-65), chromium (17-19), nickel
  (12-14)
• - Minor amounts of nitrogen, manganese,
  molybdenum, phosphorous, silicon and sulfur.
• - L low carbon content (lt0.03 wt carbon)
• Cobalt-chromium alloy (Co-Cr alloy) (Haynes 25)
• - ASTM F90
• - Cobalt (45.5-56.2), chromium (19-21),
  tungsten (14-16), nickel (9-11)
• - Minor amounts of manganese, phosphorous,
  silicon, sulfur
• - low carbon content (lt0.15 wt)
• - low iron content (lt 3 wt)
• Titanium alloy (Ti-6Al-4V)
• - ASTM F136
• - Titanium (88.3-90.8), aluminum (5.5-6.5),
  vanadium (3.5-4.5)
• - Minor amounts of hydrogen, iron, and nitrogen.
• - low carbon content (lt0.08 wt)
• - low oxygen content (lt0.13 wt)

33
In tension
Hench and Jones, Biomaterials, artificial organs,
and TE
1 GPa 103 MPa 109 N/m2 145,038 psi
34
STRESS SHIELDING

• DEFINE Osteopenia (reduced bone mass) as a
  result of removal of normal stress from the bone
  by an implant
• Metal fixation device carries too large of a
  portion of bones load
• Mechanical mis-match (modulus) of metal fixation
  devices and bone (see Table)
• May be eliminated by use of lower-modulus
  materials cp-Ti and Ti-alloys, polymers

35
Elastic Modulus
Mechanical Mismatch Issues A biomaterial that
replaces a tissue but has, for instance, higher
stiffness may be problematic (e.g. may cause
stress shielding). Similarly, if it lacks
rigidity, it may also be problematic.
36
Density
A biomaterial that replaces an equivalent volume
of tissue may have different weight as a result
of the differences in density. In some
applications, this can be problematic.
Source J. Park R.S. Lakes, Biomaterials An
Introduction (3rd Ed), p. 93 ISBN
978-0-387-3789-4
37
Alternatives to Metal Fixation Devices
What is the typical maximum elastic modulus of
polymers? Non-degradable Polymers PEEK PES and
PPS Biodegradable Polymers
38
Poly(aryl-ether-ether-ketone) (PEEK)
OPTIMA LT1 (Invibio)

• Semi-crystalline
• Tg
• High modulus, strength, wear resistance, and
  resistance to
• hydrolysis

39

• In 1990s PEEK emerged as leading
  high-performance thermoplastic for replacing
  metal orthopedic components for load bearing
  applications requiring excellent
  biocompatibility, including fracture fixation,
  spinal implants, and total joint replacement

FRACTURE FIXATION
ENDOLIGN
CFR-PEEK pins, intramedullary nails, screws, and
bone plates
40
Also
SPINAL IMPLANTS

• CFR-PEEK (carbon fiber reinforced) spinal fusion
  cage (Invibio).
• Lateral radiograph of CFR-PEEK spinal fusion
  cage\
• Note cage has tantalum microspheres for
  visualization

FYI The Brantigan spinal cage was developed to
stabilize the anterior column of the lumar or
cervical spine and facilitate fusion as treatment
for intractable back pain due to degenerative
disc disease and /or spinal instability.
41
Poly(phenylsulfones) (PPS)
Poly(ether sulfones) (PES)

• ____________________
• Tg

Solvay Advanced Polymers (Atlanta)
42
TOTAL JOINT REPLACEMENT
HIP REPLACEMENT
The hip joint is the largest load-bearing joint.
A hip joint is lined with articular cartilage a
layer of tissue that provides low-friction and
shock-absorbing properties. Arthritis and injury
can damage this protective layer of cartilage,
causing extreme pain for a patient performing
even simple activities.
43
Total Hip Replacement (THR also called total hip
arthroplasty THA)
In a hip replacement, the upper leg bone, or
femur, is separated from the hip socket, and the
damaged head is removed (A). A reamer is used to
prepare the socket for the prosthesis (B). A file
is used to create a tunnel in the femur for the
femoral stem (aka prosthesis) (C). The hip and
socket prostheses are cemented in place (and,
optionally, the femoral stem) (D), and finally
connected (E).
44
KNEE REPLACEMENT
The healthy human knee joint is aslo lined with
articular cartilage. Arthritis and injury can
similarly damage this protective layer of
cartilage causing extreme pain.
wear
http//tc.engr.wisc.edu/UER/uer01/author1/content.
html
45
In tension
Copolymer of glycolic acid and
D,L-lactide From Table 2 of Middleton article.
Some values changed to reflect other literature
values
1 GPa 103 MPa 109 N/m2 145,038 psi
46
Cemented Hip Replacement
47
What Happens?
Following implantation of a __________ ___________
__, certain ions leach out of the implant (e.g.
Ca, Si, Magnesium). These ions react with the
ions present in body fluids and
forms __________________________________which is
the mineral found in natural bone. An HCA layer
forms between the existing bone and
implant. After _______________ migrate from
existing bone into the HCA matrix, they
differentiate and proliferate and
________ ________________________at the interface
between the implant and existing bone. So, can
be used for bone tissue engineering or bone
regeneration
HCA
48
SUCCESS RATE

• In USA
• 250,000 hip 320,000 knee replacements
  annually
• Expected to increase 25 by 2030
• Hip Replacement
• Average age for hip replacement 66 years old
• 57 are women
• Success rates
• - after 10 years 90 function well
• - after 20 years 80 function well
• - after 30 years 50 function well
• Failure primarily due to implant loosening (due
  to bone loss)
• May require a revision surgery

49
STRESS SHIELDING BY METALLIC FEMORAL STEM
Can lead to implant loosening due to bone loss
around implant
50
Wear Debris Causes Bone Loss
Progressive lucent zone around acetabular
component. Steeper position of the cup indicates
migration. Subtle excentric positioning of the
femoral head is indicative of UHMWPE wear.
Illustration of the typical radiographic changes
in loosening
Loosening can even lead to femoral fracture
51
Wear of UHMWPE Acetabular Cup

• UHMWPE generates wear particles - billions to
  trillions wear particles produced (150,000 per
  step)
• - Wear rate 0.1 mm/year
• - most are lt 1 micron
• - Wear particles migrate to bone and cause
  osteolysis
• ___________________________
• immune system response to wear particles
• bone modeling balance upset
• osteoclasts (bone resorption) increases
• osteoblasts (bone building)
• Causes loss of bone, implant loosening

UHMWPE wear particle
(Courtesy of C. Schwartz, TAMU)
52
IMPROVEMENT OF UHMWPE WEAR-RESISTANCE
Sterilization of UHMWPE with _____________________
_____________ leads to crosslinking and
subsequent improved wear-resistance
Graph demonstrating a 90 reduction in wear
(measured by weight loss) at 5 million cycles
(5 years normal wear) based on hip simulator
studies
http//www.orthoassociates.com/Totalhip2.htm
53
IMPROVEMENT OF UHMWPE WEAR-RESISTANCE
54
ARTICULATING SURFACE OF HIP AND KNEE
REPLACEMENT NEW SUBSTITUTE FOR UHMWPE ?
UHMWPE (light gray bars)
30 wt CFR-PEEK (dark gray, white bars)
CFR-PEEK _____________________________ (e.g.
decreased wear rate) against CoCr, alumina,
and zirconia surfaces compared to UHMWPE
UHMWPE
small differences in processing
55
CFR-PEEK FEMORAL STEM
Without Ti mesh
EPOCH Stem FDA approved in July 2002 Core
Co-Cr-Mo alloy (forged) Middle CFR-PEEK Outer
Ti mesh to encourage bone growth (cementless)