Designing soft tissue replacements
Hydrogels as cartilage replacement devices
Gavin Braithwaite
Cambridge Polymer Group,
56 Roland Street, Suite 310
Boston, MA 02129
Cambridge
Polymer Group,
Inc.
Testing, Consultation, and Instrumentation for Polymeric Materials
7-17 Presentation (10/1/2010)
Soft-solids: Natures solution
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Hydrogels are ubiquitous in the body
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–
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–
•
Mucus and tear films
Cartilage
Vitreous humor and cornea
Tendon
Microstructure critical function
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Cambridge Polymer Group
Gels: the fourth phase of matter
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Solid
– Permanent shape, fixed volume
– Elastic recovery
•
Liquid
– Fixed volume, “conformable” shape
– No recovery (viscous)
•
Gas
– Volume expands to fill container
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Gel
– Properties between solids and liquids
– Fixed volume and shape (like solids) while static
• Often turn liquid when agitated
– Partially elastic, partially viscous (viscoelastic)
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Cambridge Polymer Group
Gel microstructure
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Gels and hydrogels
– Gel – gelatus: frozen, immobile
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Gels structure continuous solid supporting a discontinuous solvent
– Solid is usually a crosslinked or associated network of molecules
– Liquid is anything compatible with the network
•
Chemistry of network is critical
– solubility of the network “draws in” solvent to “fill” the network
– must be balanced by a “restraining” force generated within the network
• Network can’t expand beyond the length of the chain
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Cambridge Polymer Group
Characteristics of hydrogels
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High water content
–
–
–
–
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Free water allows diffusion of solutes
Viscous damping of mechanical deformation
Density “matched” to water
Very low solids content
Network structure
– Can be static or dynamic
• Permanent crosslinks (contact lenses)
• Thermally sensitive (jello)
• “labile” (hair-gel)
– Contains and confines water in 3d shape
– Provides elastic recovery
– Provides support for attaching active ingredients
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Cambridge Polymer Group
Biomedical hydrogels
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Hydrophilic polymers form network
– Polymeric backbone grown from
• monomers, oligomers or fully formed polymers
– Crosslinking
• During polymerization, post-polymerization
• Through functional groups, or addition of crosslinker
• Chemical or physical
•
Vast range of performance specifications possible
•
•
•
•
•
•
•
•
Environmental response (monomeric units)
Swellability (crosslink density and monomers)
Permeability (pore-size through crosslink density)
Viscoelastic response (monomeric units and pore size)
Biological interaction (chemistry of monomeric units)
Degradability (presence of specific monomeric units)
Gelation time (crosslinking mechanism)
Injectability (size of initial monomers/oligomers)
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Cambridge Polymer Group
Current uses of hydrogels in medicine
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Predominantly as a carrier or protector
– Drug release
• e.g. drug eluting stents
– “smart” gels
• e.g. enteric coatings (lower stomach targeted delivery)
– Tissue guides
• Nerve regeneration guides
– Vision
• Contact and intraocular lenses
– Tissue bulking
• Soft solid supports tissue
• Provides fluid motion
• Flexible and conformable
– Cartilage replacement
• Lubricious and water filled*
• But….
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Cambridge Polymer Group
Example: The knee
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Structure of joint drives function
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“Spherical” femur
“Flat” Tibia
Mutual translation and rotation
Meniscus spreads the load
Cartilage
– Biphasic
– Transitional
– Lubricious
•
Meniscus
– Reinforced
– Oriented
– Lubricious
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Cambridge Polymer Group
Disease prevalence
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Symptomatic OA (>45 yrs)
– Knee 6.7-16.7 per 100,000
– 253,000 total knees per year
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Cartilage scarring
– Due to traumatic injury
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Meniscal tears
– 61 cases per 100,000
– 850,000 surgeries per year
– Tears associated with subsequent arthritis
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In 25,000 arthroscopies 60% of patients
exhibited cartilage lesions
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Cambridge Polymer Group
Date from: The burden of musculoskeletal disease in the US
And: Baker et al. 2011
Cartilage and meniscal repair
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Cartilage
– Debridement
• Removal of damaged tissue
– Microfracture surgery
• Deliberate generation of fibrocartilage
– Ostechondral plugs
• Repair lesion through “patch”
– Autograft, allograft or synthetic
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Meniscus
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–
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Debridement
Suturing
Partial/total menisectomy with/without support
Allograft or scaffold
Primarily anchored to tibial plateau
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Cambridge Polymer Group
Cartilage properties
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Cartilage composed of collagen
– Hyaline cartilage
• Articular (lubricious)
– Elastic cartilage
• Contains elastic fibers (Epiglottis)
– Fibrocartilage
• Rough and fibrous (meniscus)
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Cartilage
Meniscus
Water content
[%]
68-85
60-70
Collagen
%
10-20
15-25
Proteoglycan
[%]
5-10
1-2
Young’s modulus
[MPa]
5-10
Tensile modulus
[MPa]
~10
UTS
[MPa]
Aggregate modulus
[MPa]
~0.7
~0.4
Permeability x 1015
[m4/N.s]
~4
~1
Friction Coeff
[]
0.1
0.08
Thickness
[mm]
0.5-5
0-10
100-200
2/5
Cambridge Polymer Group
The importance of the mensicus
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Meniscus protects cartilage
– Distributes and cushions loads
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Cartilage does not bear full load
– Tension in meniscus
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Cartilage fails through
– Trauma, arthritis, overuse
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Meniscus fails through
– Trauma, age
Femur
Femur
Meniscus
Tibia
Tibia
Without meniscus
With meniscus
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From Wilson et al (2003)
Cambridge Polymer Group
Why is this important?
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Joint replacement materials with physiological properties
– Less invasive
• thinner, conformable
– Preserve biomechanics
• similar anchoring, protects existing cartilage
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But biomechanical mimic requires similar properties
– Cartilage friendly
• Hydrophilic, lubricious and viscoelastic
– Anisotropic
• Meniscus tensile properties different from compressive
– Compound structure
• Meniscus and cartilage work together
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Design, and testing must take this into account
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Cambridge Polymer Group
Compression testing
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A1 FL0
=
L
A1L
L0
Conventional approach
F
– Compressive Modulus (e.g. ASTM D1621)
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F
stress σ
= =
E=
strain ε
Porous viscoelastic solid
A1
L0
A2
L
– Rate, total strain and fluid component matters
•
•
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Compression using different rates
Creep and recovery
Aggregate Modulus
F
Porous
endplates
Hydrogel
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Cambridge Polymer Group
Example data (PVA hydrogels)
5 mm
14 layers of unspaced coarse nylon
mesh
90
80
Strain (%)
70
60
15-28 control
50
15-28 2L coarse nylon
40
15-28 5L coarse nylon
15-28 10L coarse nylon
30
15-28 14L coarse nylon
20
Elastomer
10
1 hr. load, 0.5 MPa
0.5 hr. load, 0.05 MPa
0
0
0.5
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Time (hours)
15
1.5
Cambridge Polymer Group
stress
=
Tensile testing
strain
∆F
A1
• Conventional approach
= =
∆L
– Compressive Modulus (e.g. ASTM D1621)
L0
=
E
•
Porous viscoelastic solid
A2
∆σ
∆ε
∆FL0
A1∆L
F
– Gripping soft solids virtually impossible
L
• Make materials with grips attached
– Materials anisotropic
A1
• Must test || and _|_
L0
F
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Cambridge Polymer Group
Example data (PVA hydrogels)
Stress vs. Strain
15-28 AG 1
1.2
15-28 AG 2
15-28 AG 3
1
15-28 DP 1
15-28 DP 2
Elastomer
Stress (MPa)
0.8
15-28 DP 3
25-28 AG 1
0.6
25-28 AG 2
25-28 AG 3
0.4
25-28 DP 1
25-28 DP 2
0.2
25-28 DP 3
0
0
50
100
150
200
250
Strain (%)
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Cambridge Polymer Group
Coefficient of Friction
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•
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Various ASTM standards
More important for partial joint replacements
Measures sliding friction as a function of normal force
Sensitive to media and counterface
0.600
LB on CoCr in DI
LB on CoCr in BS
non-LB on CoCr in DI
non-LB on CoCr in BS
0.500
0.400
COF
LB=“load-bearing”
0.300
0.200
0.100
0.000
0.000
0.020
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0.040 0.060 0.080 0.100
Contact Pressure [MPa]
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0.120
0.140
Cambridge Polymer Group
Example data (PVA hydrogels)
0.60
LB on 15-28 DP in BS
LB on 15-28 RSA3 in BS
0.50
NLB on 15-28 DP in BS
NLB on 15-28 RSA3 in BS
COF
0.40
0.30
0.20
0.10
0.00
0.00
0.01
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0.02
0.03
0.04
0.05
Contact Stress [MPa]
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0.06
0.07
Cambridge Polymer Group
Design strategies
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Total replacement of the articular cartilage (TKR)
– Invasive, relieves demands on materials, engineering problem
– Removes meniscus
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Partial replacement/repair (osteochondral plug)
– Stress-shielding an issue
– Fixation and wear a concern
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Mensicus replacement
– Concerns with “intersection” line and modulus matching
– Does not directly protect cartilage surface
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Mensicus replacement with bearing zone
– More forgiving design criteria
– Requirements
• Anistropy
• Lubricious
• Hard wearing
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• Modulus close to meniscus
• Biocompatible
• Hydrated
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Cambridge Polymer Group
Possible design structure
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What would this look like?
Section view
Top view (half of a device)
Femoral head cartilage
Fiber matts
or hoops
Tibial plateau
Contact zone
Anchor point
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Cambridge Polymer Group
Soft-solids require novel designs and testing
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Designs that utilize hydrogels are closest to the natural solution
– Like the natural tissue, can only work in composite design
• Nucleus replacement, relies on annulus
– Too hard, results in end-plate failure
– Too soft, device failure (extrusion)
• Cartilage repair, needs reliable fixation method
– Hydrogels rarely have good tensile properties
– Discontinuities in designs poorly tolerated
– Wear is difficult to predict
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Tests have to take in to account the use of the material
– “simple” engineering tests no longer relevant
• stress-strain, fatigue crack, tensile etc
– Design new tests that mimic conditions likely to be encountered
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Cambridge Polymer Group
Thank you
Cambridge Polymer Group is a contract
research laboratory specializing in
polymers and their applications. We
provide outsourced research and
development, consultation and failure
analysis as well as routine analytical
testing and custom test and
instrumentation design.
Cambridge Polymer Group, Inc.
56 Roland St., Suite 310
Boston, MA 02129
(617) 629-4400
http://www.campoly.com
[email protected]
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