9 Cartilage: Anatomy, Function, Biology, Biomechanics, Injury, And Surgical Treatment

9.1 Introduction to cartilage

9.1.1 What do you know about cartilage?

@Jastifer2010Cartilage

9.1.2 Why is this topic important to engineers?

Device development
- Surgical technology, implants, diagnostics
Small lesions
- Repair, Transplant, Scaffold
When the whole joint catastrophically fails
- Joint replacement

@Geeslin2016Cartilage

(slide credit: @Geeslin2016Cartilage)

9.1.3 Outline

Articular Cartilage Composition and Microstructure – Water, collagen, proteoglycans, cells – Layers
Cartilage Subtypes
Biomechanics (tension, compression, shear)
Clinical Applications
- cartilage wear
- osteoarthritis
- cartilage repair

(slide credit: @Geeslin2016Cartilage)

9.1.4 Types of Cartilage

@OpenStaxAnatomy2020 Ch. 4

1. Cartilage is a connective tissue consisting of collagenous fibers embedded in a firm matrix of chondroitin sulfates.
1. Hyaline cartilage provides support with some flexibility. The example is from dog tissue.
1. Fibrocartilage provides some compressibility and can absorb pressure.
1. Elastic cartilage provides firm but elastic support. From top, LM × 300, LM × 1200, LM × 1016. (Micrographs provided by the Regents of University of Michigan Medical School © 2012)

(slide credit: @OpenStaxAnatomy2020 Ch. 4)

9.1.5 Cartilage subtypes

Physeal: growth plate
Fibrocartilage: tendon/ligament bony insertion
Elastic: trachea
Fibroelastic: meniscus
Hyaline: articular

(slide credit: @Geeslin2016Cartilage)

9.1.6 Fibrocartilage - enthesis

@Geeslin2016Cartilage

Apostolakos et al, Musc Lig Tend J 2014

(slide credit: @Geeslin2016Cartilage)

9.2 Tendon healing

@Geeslin2016Cartilage

Rodeo, J Shoulder Elbow Surg 2007

(slide credit: @Geeslin2016Cartilage)

9.3 Meniscus

Crescent shaped
Anchored to the tibia via anterior/posterior roots, capsule
Force distribution

@Geeslin2016Cartilage

(slide credit: @Geeslin2016Cartilage)

9.4 Contact mechanics

Accepted metric for evaluating joint forces
Pressure = Force/Area
- Force = Pressure x Area
- Reciprocally related

Contact pressure “map”

@Geeslin2016Cartilage

Geeslin et al, Knee Surg Sports Traum 2015

(slide credit: @Geeslin2016Cartilage)

9.5 Meniscus

@Geeslin2016Cartilage

Inhomogeneous and (B) anisotropic tensile stiffness

Orthopaedic Sports Medicine. Delee and Drez, Ch 45

(slide credit: @Geeslin2016Cartilage)

9.6 Meniscus repair

@Geeslin2016Cartilage

Repair of radial meniscus tear
PRP augmentation of repair
Platelet rich plasma, mix of growth factors

(slide credit: @Geeslin2016Cartilage)

9.7 Articular cartilage composition, microstructure

Typical total thickness: 2-4 mm
Chondrocytes: cartilage cells
Extracellular Matrix (ECM)
- Predominant component is H2O
- Type II collagen, Proteoglycans
- Charged molecules, ions
Fractional composition varies by zone
Avascular, aneural

(slide credit: @Geeslin2016Cartilage)

9.8 Chondrocytes

Sparsely distributed in articular cartilage
5% of wet weight; <10% of volume
Responsible for the synthesis and maintenance of organic component of the extracellular matrix (ECM)

(slide credit: @Geeslin2016Cartilage)

9.9 Chondrocytes

@Geeslin2016Cartilage

Jazrawi et al. J Am Acad Orthop Surg 2011

(slide credit: @Geeslin2016Cartilage)

9.10 Collagen

Type II in Hyaline, Type I in Fibrocartilage
Accounts for 10-20% of wet weight
Important for tensile strength
Very stable; $T_{\frac{1}{2}}$ ~25 years
Tropocollagen is basic biological unit
- Consists of three α-chains
- Cross-linking between tropocollagen molecules results in high tensile strength

(slide credit: @Geeslin2016Cartilage)

9.11 Collagen

@Geeslin2016Cartilage

(slide credit: @Geeslin2016Cartilage)

9.12 Proteoglycans

Complex macromolecules
Important for providing compressive strength
- Attract water, ions
Building blocks
- Central protein core with polysaccharide chains
- Aggrecans: large aggregating proteoglycans with >100 sidechains
- Aggregate macromolecule: aggrecans bound to HA

(slide credit: @Geeslin2016Cartilage)

9.13 Proteoglycans

@Geeslin2016Cartilage

Ulrich-Vinther et al. J Am Acad Orthop Surg 2003

(slide credit: @Geeslin2016Cartilage)

9.14 Water, ions

Water – Accounts for 70-90% of wet weight – Avascular tissue; H2O allows movement of gases, waste products, nutrients to chondrocytes
Ions – Cations (Na+ and Ca2+) are attracted to negatively charged proteoglycans for electrical neutrality
- Mechanical influence – Fluid flow is important contribution – Joint lubrication

(slide credit: @Geeslin2016Cartilage)

9.15 Articular cartilage zones

@Geeslin2016Cartilage

Ulrich-Vinther et al. J Am Acad Orthop Surg 2003

(slide credit: @Geeslin2016Cartilage)

9.16 Articular cartilage

Millions of cycles required in a lifetime
The body has an efficient method of allowing activity while minimizing wear to the joint surface

@Geeslin2016Cartilage

(slide credit: @Geeslin2016Cartilage)

9.17 Hyaline Cartilage and Synovial Joints

@Geeslin2016Cartilage

Bartel refers to “articular cartilage”
Allows joints to have a wide range of motion
Joint surfaces covered with 2-4 mm of hyaline cartilage
Suited to withstand rigors of joint environment without failing due to cyclic loading
- Isolated tissue
- Distinct from bone
- Devoid of blood supply, nerves
- Cellular density less than any other tissue

(slide credit: @Jastifer2010Cartilage)

9.18

@Geeslin2016Cartilage

Controlled laboratory study
Weight-bearing running 75 minutes, 3.3 km/hr, 5 days per week, 527 weeks, 130% body weight
No difference on LM or mechanical properties

(slide credit: @Geeslin2016Cartilage)

9.19 Friction at articular surfaces

Joint/Material	Coefficient of Friction
Human Knee	0.005-0.02
Human Hip	0.01-0.04
Steel on Steel	0.6-0.8
Teflon on teflon	0.04
Metal on Polyethylene	0.2-0.4

(slide credit: @Geeslin2016Cartilage)

9.20 Mechanical properties

Anisotropy: directioonally dependent; difficult to model mathematiocally
Biphasic – Intrinsic: ﬂow-independent behavior of collagenproteoglycan matrix – Flow of intersHHal ﬂuid through the matrix and resistance of matrix to the ﬂow
Intrinsic propertioes are not representatiove of in vivo behavior, however, they largely determine ﬂuid ﬂow

(slide credit: @Geeslin2016Cartilage)

9.21 Equilibrium stressstrain behavior

Can be determined from steady-state response of tensile creep loading with no ﬂuid ﬂow
Linear up to strains of 15%
Modulus ~ 4-10 MPA depending on specimen locatioon in joint

(slide credit: @Geeslin2016Cartilage)

9.22 Uniaxial tensile test

@Bartel2006

Low constant strain rate
- Values higher than “equilibrium” due to dynamic nature of test
Some ﬂuid ﬂow occurs
Dynamic Young’s modulus, from linear region, is ~ 40-400 MPa

Bartel. Orthopaedic Biomechanics. Ch 4.2.

(slide credit: @Geeslin2016Cartilage)

9.23 Intrinsic compressive properties

Aggregate modulus $H_A$
- RaHo of equilibrium stress to equilibrium strain
- Typical values 0.3-1.3 MPa
Compressive equilibrium
- Depends on repulsive electrical charges of PG, increases with increased PG content (next slide)
- Unrelated to collagen content (structurally) although collagen constrains separation of PG, resulting in internal tensile stresses

(slide credit: @Geeslin2016Cartilage)

9.24 Shear

@Bartel2006

Flow-independent shear rigidity of cartilage likely due to collagen ﬁbers PG likely interact to support matrix

(slide credit: @Geeslin2016Cartilage)

9.25 Shear: collagen and modulus

@Bartel2006

(slide credit: @Geeslin2016Cartilage)

9.26 Creep

@Geeslin2016Cartilage

Material subjected to a constant load
Rapid initial deformation followed by progressive deformation until equilibrium
This property is due to ﬂuid ﬂow which is not instantaneous

(slide credit: @Geeslin2016Cartilage)

9.27 Stress relaxation

@Geeslin2016Cartilage

Material subjected to constant deformation
High initial stress
Progressive decrease in the stress required to maintain deformation

Mow et al. J Biomech 1984

(slide credit: @Geeslin2016Cartilage)

9.28 Creep and stress relaxation

@Geeslin2016Cartilage

Orthopaedic Sports Medicine. DeLee and Drez, ed. Ch 45

(slide credit: @Geeslin2016Cartilage)

9.29 Permeability

Permeability, κ, is the ease of ﬂuid ﬂow
As cartilage is compressed (and ﬂuid ﬂows from cartilage) the permeability decreases (with increased strain), and stiffness increases which prevents further loss of ﬂuid

(slide credit: @Geeslin2016Cartilage)

9.30 Clinical correlates

@Bartel2006

Disruption of the collagen ﬁbril meshwork allows the PG to expand, increases [H2O], decreases [PG]
Less repulsive electrostatic forces to resist loading
Decrease in cartilage stiffness, increase in matrix permeability
In osteoarthritis, decreased PG and increased H2O - Greater deformation - Altered mechanotransduction?

(slide credit: @Geeslin2016Cartilage)

9.31 Surgical repair

@Geeslin2016Cartilage

Microfracture – Results in fibrocartilage repair
Autologous Osteochondral Transplantation – Harvest of viable hyaline cartilage from NWB surface, transfer to defect

Bedi et al. J Bone Jt Surg Am 2010.

(slide credit: @Geeslin2016Cartilage)

9.32 Microfracture – 2 years

@Geeslin2016Cartilage

(slide credit: @Geeslin2016Cartilage)

9.33 Surgical repair

@Geeslin2016Cartilage

Fresh frozen allograph (cadaver)
MRI demonstrates incorporation, isointense cartilage signal

Bedi et al. J Bone Jt Surg Am 2010.

(slide credit: @Geeslin2016Cartilage)

9.34 Evidence based medicine

@Geeslin2016Cartilage

Bedi et al. J Bone Jt Surg Am 2010.

(slide credit: @Geeslin2016Cartilage)

9.35 Future directions

Chondral scaffolds
Osteochondral scaffolds
PRP?
Mesenchymal stem cells
Isolated growth factors
Quantitative MRI

(slide credit: @Geeslin2016Cartilage)

9.36 Chondral scaffolds

@Geeslin2016Cartilage

Chondral scaffolds
- E.g. juvenile, adult
- Fibrin glue
Autologous chondrocyte implantation
- Ex vivo expansion
- Implantation under periostealpatch or other matrix

(slide credit: @Geeslin2016Cartilage)

9.37

Biocartilage (Arthrex) (Hirahara Sports Med Arthrosc 2015)

“…dehydrated allograft cartilage ECM scaffold and can stimulate autologous cellular interactions. The ECM is made up of type II collagen, proteoglycans, and cartilaginous growth factors, which are components of native cartilage”

DeNovo (Zimmer) (Farr AJSM 2014; Farr Cartilage 2011) > “…consists of allograft articular cartilage from donors younger > than 13 years old that has been cut into approximately 1-mm > cubes. It is applied to cartilage lesions in a monolayer and held > in place with the use of fibrin sealant” (particulated juvenile > allograft)

Neocart (Histogenics) (DeBerardino Sports Med Arthrosc 2015) > “3-dimensional type-I collagen scaffold seeded with autologous > chondrocytes”

(slide credit: @Geeslin2016Cartilage)

9.38 Osteochondral scaffolds

@Geeslin2016Cartilage

(slide credit: @Geeslin2016Cartilage)

9.39 Biologics

PRP?
Mesenchymal stem cells
Isolated growth factors

@Geeslin2016Cartilage

(slide credit: @Geeslin2016Cartilage)

9.39.1 3 Types of Cartilage

Hyaline (most commonly thought of)
- Lines synovial joints (joints that contain synovial fluid)
- Dense, translucent, connective tissue
Fibrocartilage
- Transitional cartilage found at the margins of some joint capsules
- Joint capsules
- Insertions of ligaments and tendons into bone
- Menisci, Annulus fibrosus (vertebral disc) Elastic cartilage
- External ear
- Eustacian tube, epiglottis, and parts of the larynx

(slide credit: @Jastifer2010Cartilage)

9.39.2 Hyaline Cartilage and Synovial Joints

Bartel refers to “articular cartilage”
Allows joints to have a wide range of motion
Joint surfaces covered with 2-4 mm of hyaline cartilage
Suited to withstand rigors of joint environment without failing due to cyclic loading
- Isolated tissue
- Distinct from bone
- Devoid of blood supply, nerves
- Cellular density less than any other tissue

(slide credit: @Jastifer2010Cartilage)

9.39.3 Primary Functions of Articular Cartilage

Distribute joint loads over a wide area in order to decrease stress sustained by contacting joint surfaces
Allow relative movement of opposing joint surfaces, while minimizing friction and wear
Essential for growth and, development of bone
- Less important to engineers

(slide credit: @Jastifer2010Cartilage)

9.39.4 Composition and Structure of Articular Cartilage

@Jastifer2010Cartilage

Chondrocytes (cartilage cells)
Matrix

(slide credit: @Jastifer2010Cartilage)

9.39.5 Composition and Structure of Articular Cartilage

Chondrocytes (cartilage cells)
- Sparsely distributed cells in articular cartilage
- Less than 10% of tissue volume
- Manufacture, secrete, and maintain organic component of extracellular matrix (ECM)

(slide credit: @Jastifer2010Cartilage)

9.39.6 Chondrocyte Distribution in Articular Cartilage

STZ (10-20%)
- Chondrocytes oblong, parallel to articular surface
Middle Zone (40-60%)
- Chondrocytes round
Deep Zone (30%)
Calcified Zone
- Chondrocytes arranged in columnar fashion
Subcondral Bone
- between calcified and noncalcified tissue

@Jastifer2010Cartilage

(slide credit: @Jastifer2010Cartilage)

9.39.7 Chondrocyte Distribution in Articular Cartilage

STZ (10-20%)
- Chondrocytes oblong, parallel to articular surface
Middle Zone (40-60%)
- Chondrocytes round
Deep Zone (30%)
Calcified Zone
- Chondrocytes arranged in columnar fashion
Subcondral Bone
- between calcified and noncalcified tissue

@Jastifer2010Cartilage

(slide credit: @Jastifer2010Cartilage)

9.39.8 Composition and Structure of Articular Cartilage (continued)

Organic matrix
- Composed of dense framework of type II collagen fibrils enmeshed in concentration of proteoglycans (PG)
- Collagen (15-22% of wet weight)
- Proteoglycans (4-7% of wet weight)
- 60-85% water content, inorganic salts, other proteins, glycoproteins, and lipids

(slide credit: @Jastifer2010Cartilage)

9.39.9 Composition and Structure of Articular Cartilage (continued)

Collagen and Proteoglycans
- Form structural components that support mechanical stresses applied to cartilage
- Together with water determine biomechanical behavior of cartilage

(slide credit: @Jastifer2010Cartilage)

9.39.10 Collagen

Most abundant protein in the body
- Think of it structurally as a rope
Provides fibrous ultrastructure in cartilage
Tropocollagen is basic biological unit of collagen
- Composed of 3 alpha chains coiled in left hand helices
- Alpha chains coiled around each other in right hand triple helix
- Form tropocollagen molecules
- Cross links formed between tropocollagen molecules high tensile strength

@Jastifer2010Cartilage

(slide credit: @Jastifer2010Cartilage)

9.39.11 Collagen Structure

@Jastifer2010Cartilage

(slide credit: @Jastifer2010Cartilage)

9.39.12 Structure of Collagen in Articular Cartilage

Inhomogeniously distributed
Three zones
- Superficial tangential zone (STZ)
  - Zone with highest concentration of collagen
- Middle zone
  - Collagen fibers randomly distributed and farther apart
- Deep zone

(slide credit: @Jastifer2010Cartilage)

9.39.13 Arrangement of Collagen in Articular Cartilage

@Jastifer2010Cartilage

Randomly layered fibrils of collagen to accommodate the high concentration of proteoglycans and water
Pattern of collagen fibril arrangement related to tensile stiffness and strength characteristics.
Note correspondence between collagen and chondrocyte arrangement.

(slide credit: @Jastifer2010Cartilage)

9.39.14 Strength of Collagen

@Jastifer2010Cartilage

Strong in tension
Weak in compression (high slenderness ratio: length/width)

(slide credit: @Jastifer2010Cartilage)

9.40 Material Properties of Articular Cartilage

Anisotropic – differ with direction of loading (may be associated with zonal arrangement of collagen)
“Split lines” – surface collagen fiber pattern; functionally related to tensile strength
Referred to in Bartel p133

@Jastifer2010Cartilage

(slide credit: @Jastifer2010Cartilage)

9.40.1 Proteoglycan (PG)

Large protein-polysaccharide molecules that exist as either monomers or as aggregates
PG aggregation promotes immobilization of the PG’s within the collagen meshwork adding structural rigidity to the extracellular matrix of articular cartilage

(slide credit: @Jastifer2010Cartilage)

9.40.2 Proteoglycan Aggregate

(-) charge

@Jastifer2010Cartilage

(slide credit: @Jastifer2010Cartilage)

9.40.3 Water

Most abundant component of articular cartilage
80% concentrated near articular surface
Contains many mobile cations that greatly influence the mechanical and physiochemical behaviors of cartilage, and balance negative charge of PG’s (sodium, calcium)
Essential to health of avascular cartilage (permits movement of gasses, nutrients, and waste products between chondrocytes and surrounding nutrient-rich synovial fluid)
Movement of water (up to 70% under load) important in
- controlling cartilage mechanical behavior
- joint lubrication

(slide credit: @Jastifer2010Cartilage)

9.40.4 Interaction Among Cartilage Components

Collagen and proteoglycans interact to form a porous composite fiber-reinforced organic solid matrix that is swollen with water
Collagen-PG solid matrix and interstitial fluid protect against high levels of stress and strain developing in the ECM when articular cartilage subjected to external loads

(slide credit: @Jastifer2010Cartilage)

9.41 Organization of Cartilage

@Bartel2006

(slide credit: @Jastifer2010Cartilage)

9.42 Biomechanical Loading of Articular Cartilage

Forces at joint surface vary from zero to several times body weight
“Contact” area varies in a complex manner; typically only several square centimeters
Potentially high pressures
Think of cartilage behavior with load as biphasic (solid component and water) … wet sponge?

(slide credit: @Jastifer2010Cartilage)

9.42.1 Arrangement of Collagen in Articular Cartilage

Superficially:
- Tangential orientation of collagen resists shear as joint surfaces move past each other

@Jastifer2010Cartilage

(slide credit: @Jastifer2010Cartilage)

9.42.2 Arrangement of Collagen in Articular Cartilage

@Jastifer2010Cartilage

Middle:
- High water content, high PG content
- With early load, water moves to joint space and participates in lubrication With late load, negative charge of PG molecules begin to repulse each other and offer resistance to compression
- Fairly isotropic

(slide credit: @Jastifer2010Cartilage)

9.42.3 Viscoelasticity

-Cartilage is viscoelastic - Hysteresis - Strain rate dependent on time - Creep - Stress relaxation

(slide credit: @Jastifer2010Cartilage)

9.42.4 Mechanical testing

(slide credit: @Jastifer2010Cartilage)

9.43 Intrinsic compressive properties

@Bartel2006

Confined compression creep test: is a uniaxial strain test.
- confined chamber so deformation can only occur along axis of loading,
- an applied constant stress,
- fluid can escape through porous surface,
- creep occurs and eventually equilibrium (steady-state is reached when ﬂuid ﬂow stops)
Experiment is repeated over varius stresses and respective strains and aggreate modulus $H_A$ is obtained (typically 0.3-1.3 MPa)

(slide credit: @Jastifer2010Cartilage, @Geeslin2016Cartilage)

9.44 Intrinsic compressive properties

Early load results in ﬂuid efflux
Late load results in increased charge density due to negative PG side-chains

@Geeslin2016Cartilage

(slide credit: @Geeslin2016Cartilage)

9.45 Intrinsic compressive properties

@Bartel2006

(slide credit: @Geeslin2016Cartilage)

9.45.1 Compression test of cartilage plug

(Mow 1977) - Stress Relaxation - Nonlinear phenomenon

@Jastifer2010Cartilage

(slide credit: @Jastifer2010Cartilage)

9.45.2 Shear Stress

High poison’s ratio, thus normal load leads to large lateral displacement relative to bone thus high shear stresses at cartilage/bone interface

Not intuitive but joints aren’t normal, and thus see shear stress

@Jastifer2010Cartilage

(slide credit: @Jastifer2010Cartilage)

9.45.3 Pure Shear

Small torsional displacements of cylindrical samples (which produce pure shear), result in no volume change of the cartilage to drive fluid flow. The interstitial fluid (water) has low viscosity and does not make an appreciable contribution to resisting shear. Therefore, the resistance to shear is due to the solid matrix. Tests of cartilage in shear show that the matrix behaves as a viscoelastic solid

@Jastifer2010Cartilage

(slide credit: @Jastifer2010Cartilage)

9.45.4

Pure shear is equivalent to a combination of tension and compression applied at +/-45 degrees to the plane of shear

@Bartel2006

(slide credit: @Jastifer2010Cartilage)

9.45.5

If shear can be thought of as partially a tensile force and collagen resists tensile forces, then an increase in collagen content should increase resistance to shear:

@Bartel2006

(slide credit: @Jastifer2010Cartilage)

9.45.6

Likewise for compression and proteoglycan content

@Bartel2006

(slide credit: @Jastifer2010Cartilage)

9.45.7

Less water means less proteoglycan per unit volume? Also a function of ageing

@Bartel2006

(slide credit: @Jastifer2010Cartilage)

9.45.8 Creep Test

Constant load
Deformation is not instantaneous, as it would be in a single-phase elastic material such as a spring.
Displacement of the cartilage is a function of time, since the fluid cannot escape from the matrix instantaneously
Initially, the displacement is rapid. This corresponds to a relatively large flow of fluid out of the cartilage. As the rate of displacement slows and the displacement approaches a constant value, the flow of fluid likewise slows.
Equilibrium takes several thousand seconds

@Jastifer2010Cartilage

(slide credit: @Jastifer2010Cartilage)

9.45.9 Creep Test

Biphasic model consideration leads to:
- Aggregate modulus
  - Modulus at equilibrium 0.5 to 0.9 MPa (referred to Young’s modulus of cartilage
- Permeability
  - Resistance to flow

@Jastifer2010Cartilage

(slide credit: @Jastifer2010Cartilage)

9.45.10 Permeability

Flow velocity proportional to pressure gradient
$10^{-15}$ to $10^{-16} m$^4$/Ns
If a pressure difference of 210,000 Pa (about the same pressure as in an automobile tire) is applied across a slice of cartilage 1 mm thick, the average fluid velocity will be only 1*$10^{-8}$ m/s, which is about 100 million times slower than normal walking speed

(slide credit: @Jastifer2010Cartilage)

9.46

@Jastifer2010Cartilage

(slide credit: @Jastifer2010Cartilage)

9.47

@Bartel2006

As you compress the tissue, you do two things: - close the space for water to flow through by compacting tissue, also - increase charge density thus slowing flow.

(slide credit: @Jastifer2010Cartilage)

9.48 Putting it together

As you stand
- Complex interaction of stress in the cartilage matrix and pressure in the fluid.
- Cartilage stops itself from “bottoming out” because its permeability decreases with increased strain, and it’s stiffness increases.
- Cartilage has to be thought of as a dynamic structure (see example 4.2)

(slide credit: @Jastifer2010Cartilage)

9.49 Clinical Correlate

Arthritic cartilage has a lower modulus and increased permeability (higher water content, lower proteoglycan content).
This leads to greater and more-rapid deformation than normal.
Theoretically, these changes may influence the metabolic activity of the chondrocytes, which are known to respond to their mechanical environment (mechanotransduction).

@Jastifer2010Cartilage

(slide credit: @Jastifer2010Cartilage)

9.50 Clinical Correlate

Cartilage thought to fail in tension/shear at surface that creates a fissure that propagate
Femoral head arthritis far more likely than talus arthritis

@Jastifer2010Cartilage

(slide credit: @Jastifer2010Cartilage)

9.51 Clinical Correlate

Old cartilage fails earlier than young cartilage

@Jastifer2010Cartilage

(slide credit: @Jastifer2010Cartilage)

9.52 Clinical correlate

@Geeslin2016Cartilage

Hypothesis: - Cartilage thought to fail in tension/ shear at surface that creates a fissure that propagate

Fact: - Femoral head arthritis far more likely than talus arthritis

(slide credit: @Geeslin2016Cartilage)

9.53 Clinical correlate

@Geeslin2016Cartilage

Old cartilage fails earlier than young cartilage

(slide credit: @Geeslin2016Cartilage)

9.54 Lubrication of Articular Cartilage

Synovial joints subjected to enormous range of loading conditions
Cartilage typically sustains little wear

(slide credit: @Jastifer2010Cartilage)

9.54.0.0.1 -Implication:

Sophisticated lubrication process required

(slide credit: @Jastifer2010Cartilage)

9.55 Joint Lubrication

Amazing engineering feat
Coefficient of friction of cartilage on cartilage somewhere around 0.001!!!!
Compare to teflon on teflon .04

(slide credit: @Jastifer2010Cartilage)

9.56 Lubrication Processes for Articular Cartilage

@Jastifer2010Cartilage

(slide credit: @Jastifer2010Cartilage)

9.57 Boundary Lubrication

Synovial fluid constituent responsible for boundry lubrication - glycoprotein – lubricin or - phospholipid – dipalmitoyl

phosphatidylcholine ??

@Jastifer2010Cartilage

(slide credit: @Jastifer2010Cartilage)

9.58 Boundary Lubrication

Surfaces of cartilage protected by a layer of boundary lubricant
- Direct surface-to-surface contact is prevented
- Most surface wear eliminated
- Lubricin (glycoprotein) synovial fluid constituent responsible for boundary lubricant
  - Absorbed as monolayer to each articular surface
  - Able to carry loads (normal forces) and reduce friction
Independent of physical properties of lubricant (e.g., viscosity) and bearing material (e.g., stiffness)
Primarily depends on chemical properties of lubricant
Functions under high loads at low relative velocities, preventing direct contact between surfaces

(slide credit: @Jastifer2010Cartilage)

9.59 Modes of Mixed Lubrication

Combination of fluid-film and boundary lubrication
Temporal coexistence of fluid-film and boundary lubrication at spatially distinct locations
Joint surface load sustained by fluid-film and boundary lubrication Most friction in boundary lubricated areas; most load supported by fluid-film

@Jastifer2010Cartilage

(slide credit: @Jastifer2010Cartilage)

9.60 Lubrication Processes for Articular Cartilage

@Jastifer2010Cartilage

(slide credit: @Jastifer2010Cartilage)

9.61 Fluid-film Lubrication

Thin film of lubricant separates bearing surfaces
Load on bearing surfaces supported by pressure developed in fluid-film
Lubrication characteristics determined by lubricant’s properties
- Rheological properties
- Viscosity and elasticity
- Film geometry
- Shape of gap between surfaces
- Speed of relative motion of two surfaces

(slide credit: @Jastifer2010Cartilage)

9.62 Lubrication Processes for Articular Cartilage

@Jastifer2010Cartilage

(slide credit: @Jastifer2010Cartilage)

9.63 Hydrodynamic Lubrication

Occurs when 2 nonparallel rigid bearing surfaces lubricated by a fluid-film that moves tangentially with respect to each other
Wedge of converging fluid formed
Lifting pressure generated in wedge by fluid viscosity as the bearing motion drags fluid into gap

(slide credit: @Jastifer2010Cartilage)

9.64 Schematic of Hydrodynamic Lubrication

@Jastifer2010Cartilage

(slide credit: @Jastifer2010Cartilage)

9.65 Schematic of Hydrodynamic Lubrication

@Jastifer2010Cartilage

(slide credit: @Jastifer2010Cartilage)

9.66 Lubrication Processes for Articular Cartilage

@Jastifer2010Cartilage

(slide credit: @Jastifer2010Cartilage)

9.67 Squeeze-film Lubrication

Occurs when weight bearing surfaces move perpendicularly toward each other
Wedge of converging fluid formed Pressure in fluid-film result of viscous resistance of fluid that acts to impede its escape from the gap
Sufficient to carry high loads for short durations (eventually contact between asperities in bearing surfaces)

(slide credit: @Jastifer2010Cartilage)

9.68 Schematic of Squeeze-film Lubrication

@Jastifer2010Cartilage

(slide credit: @Jastifer2010Cartilage)

9.69 Schematic of Squeeze-film Lubrication

@Jastifer2010Cartilage

(slide credit: @Jastifer2010Cartilage)

9.70 Articular Cartilage Asperities and Lubrication

Articular cartilage not perfectly smooth; asperities
Fluid film lubrication in regions of cartilage non-contact
Boundary lubricant (lubricin) in areas of asperities
Low rates of interfacial wear suggests that asperity contact rarely occurs in articular cartilage

(slide credit: @Jastifer2010Cartilage)

9.71 Asperities in Articular Cartilage

@Jastifer2010Cartilage

(slide credit: @Jastifer2010Cartilage)

9.72 Lubrication Processes for Articular Cartilage

@Jastifer2010Cartilage

(slide credit: @Jastifer2010Cartilage)

9.73 Modes of Mixed Lubrication

Boosted lubrication
- Shift of fluid-film to boundary lubrication with time over the same location
- Articular surfaces protected during loading by ultrafiltration of synovial through the collagen-PG matrix

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(slide credit: @Jastifer2010Cartilage)

9.74 Modes of Mixed Lubrication

Boosted lubrication (continued)
- Solvent component of synovial fluid passes into the articular cartilage during squeeze-film action yielding a concentrated gel of HA protein complex that coats and lubricates the surfaces
- As articular surfaces approach each other, difficult for HA macromolecules to escape from gap between surfaces

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(slide credit: @Jastifer2010Cartilage)

9.75 Variation of Lubrication Processes for Articular Cartilage

Elastohydrodynamic Lubrication - associated with deformable articular cartilage - pressure from fluid-film deforms surfaces Fluid-film Lubrication

Hydrodynamic Lubrication

Boundary Lubrication

Squeeze-film Lubrication

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(slide credit: @Jastifer2010Cartilage)

9.76 Comparison of Hydrodynamic and Squeeze-film Lubrication under Rigid and Elastodynamic Conditions

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(slide credit: @Jastifer2010Cartilage)

9.77 Elastohydrodynamic Lubrication

Beneficial increase in surface areas
- Lubricant escapes less rapidly from between the bearing surfaces
- Longer lasting lubricant film generated
- Stress of articulation lower and more sustainable
Elastohydrodynamic lubrication greatly increases load bearing capacity

(slide credit: @Jastifer2010Cartilage)

9.78 Dynamic Relationship between Vertical Load and Hip Joint

Lubrication

Support phase

Swing phase

Support phase

Swing phase

Initial load on hip at heel contact likely supported by hydrodynamic lubrication
Small vertical load on hip articular cartilage supported by hydrodynamic lubrication
As load continues, fluid is squeezed between articular surfaces and is supported more by squeeze-film lubrication

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(slide credit: @Jastifer2010Cartilage)

9.79 Dynamic Relationship between Vertical Load and Hip Joint

Lubrication

Time = start - Load on hip supported by squeeze-film lubrication

Time = 3 minutes - Over time fluid-film may be eliminated and surfaceto-surface contact may occur

time = start time = 3 minutes

Surfaces protected by thin layer of ultrafiltrated synovial gel (boosted lubrication) or by the adsorbed lubricin monolayer (boundary lubrication)

@Jastifer2010Cartilage

(slide credit: @Jastifer2010Cartilage)

9.80 Two Types of Wear of Articular Cartilage

Interfacial – due to interaction between bearing surfaces
- Adhesion wear – surface fragments from bearing surfaces in contact with each other adhere and are torn away
- Abrasion wear – soft material is scraped by hard material (opposing surface or loose particles)

===========================================

*Effective joint lubricating system makes interfacial wear unlikely under normal articular cartilage conditions
*Interfacial wear may take place in an impaired or degenerated synovial joint

===========================================

Fatigue wear
- due to accumulation of microscopic damage within the bearing material under repetitive stress; not from surface-to-surface contact
- Bearing surface failure from repeated application of high loads over short period of time or repetition of low loads over long period of time

(slide credit: @Jastifer2010Cartilage)

9.81 Potential Methods for Articular Cartilage Degeneration

Magnitude of imposed stresses
Total number of sustained stress peaks
Change in the collagen-PG matrix
Change in mechanical properties of the tissue

(slide credit: @Jastifer2010Cartilage)

9.82 Articular Surface of Cartilage

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(slide credit: @Jastifer2010Cartilage)

9.83 Characteristics

Chondrocytes (cartilagecells)
- Located in lacunae
Extensive extra-cellular matrix
Fibers, ground substance
Collagen, hyaluronic acid, proteoglycans, glycoproteins, elastic (in elastic cartilage)
Macromolecules, water, fibers bind together and give firm, flexible properties to tissue.
No blood or nerve supply
Low metabolic rate.

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(slide credit: @Jastifer2010Cartilage)

9.84 Perichondrium

Dense connective tissue that covers cartilage (except articular cartilage of joints.)
Contains blood, nerve supply, lymphatics.
Contains collagen fibers, fibroblasts

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(slide credit: @Jastifer2010Cartilage)

9.84.1

@Bartel2006

9.85 Cartilage Mechanics (Jastifer Lecture)

Question:

Orthopedic surgeons refer to cartilage as a a shock absorber, do you agree? Why?

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9.86

Wolff’s Law

“Bone in a healthy person or animal will adapt to the loads it is placed under” -Late 1800’s

1960’s

According to this a typical bone, e.g. the tibia has a security margin of about 5 to 7 between typical load (2000 to 3000 μStrain) and fracture load (about 15000μStrain).

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Mechanotransduction

http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=mechano&part=A1859

This same effect is seen in Tendons, Ligaments, Muscle, Bone, and to lesser extent Cartilage

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What do you know about cartilage?

Hyaline (most commonly thought of)

Fibrocartilage

Lines synovial joints (joints that contain synovial fluid) Dense, translucent, connective tissue Transitional cartilage found at the margins of some joint capsules Insertions of ligaments and tendons into bone Menisci, Annulus fibrosus (vertebral disc)

Elastic cartilage

External ear Eustacian tube, epiglottis, and parts of the larynx

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Hyaline Cartilage and Synovial Joints

Activity throughout a lifetime requires millions of joint cycles Body has developed an efficient way to deal with activity while minimizing wear

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Hyaline Cartilage and Synovial Joints

Bartel refers to “articular cartilage” Allows joints to have a wide range of motion Joint surfaces covered with 2-4 mm of hyaline cartilage

Suited to withstand rigors of joint environment without failing due to cyclic loading Isolated tissue

Distinct from bone Devoid of blood supply, nerves Cellular density less than any other tissue

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Primary Functions of Articular Cartilage

Distribute joint loads over a wide area in order to decrease stress sustained by contacting joint surfaces

Allow relative movement of opposing joint surfaces, while minimizing friction and wear

Essential for growth and, development of bone

Less important to engineers

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Composition and Structure of Articular Cartilage Chondrocytes (cartilage cells) Matrix

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Composition and Structure of Articular Cartilage

Chondrocytes (cartilage cells) Sparsely

distributed cells in articular

cartilage Less than 10% of tissue volume Manufacture, secrete, and maintain organic component of extracellular matrix (ECM)

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Chondrocyte Distribution in Articular Cartilage Chondrocytes oblong, parallel to articular surface

Chondrocytes round

Chondrocytes arranged in columnar fashion

-between calcified and noncalcified tissue

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Chondrocyte Distribution in Articular Cartilage Chondrocytes oblong, parallel to articular surface

Chondrocytes round

Chondrocytes arranged in columnar fashion

-between calcified and noncalcified tissue

Composition and Structure of Articular Cartilage (continued)

Extracellular matrix (figure 4.8) Composed

of dense framework of type II collagen fibrils enmeshed in concentration of proteoglycans (PG) Collagen

(15-22% of wet weight) Proteoglycans (4-7% of wet weight) 60-85% water content, inorganic salts, other proteins, glycoproteins, and lipids

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Composition and Structure of Articular Cartilage (continued)

Collagen and Proteoglycans Form

structural components that support mechanical stresses applied to cartilage Together with water determine biomechanical behavior of cartilage

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Collagen

Most abundant protein in the body

Think of it structurally as a rope

Tropocollagen is basic biological unit of collagen Composed of 3 alpha chains coiled in left hand helices Alpha chains coiled around each other in right hand triple helix Form tropocollagen molecules Cross links formed between tropocollagen molecules  high tensile strength

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Collagen Structure

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Structure of Collagen in Articular Cartilage Inhomogeniously distributed Three zones

Superficial Zone

Middle

tangential zone (STZ)

with highest concentration of collagen

zone

Collagen fibers randomly distributed and farther apart

Deep zone

Arrangement of Collagen in Articular Cartilage

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Arrangement of Collagen in Articular Cartilage

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Randomly layered fibrils of collagen to accommodate the high concentration of proteoglycans and water

•Pattern of collagen fibril arrangement related to tensile stiffness and strength characteristics. •Note correspondence between collagen and chondrocyte arrangement.

Strength of Collagen

Strong in tension Weak in compression (high slenderness ratio: length/width)

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Material Properties of Articular Cartilage

Anisotropic – differ with direction of loading (may be associated with zonal arrangement of collagen) “Split lines” – surface collagen fiber pattern; functionally related to tensile strength Referred to in Bartel p133

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Proteoglycan (PG) Large protein-polysaccharide molecules that exist as either monomers or as aggregates PG aggregation promotes immobilization of the PG’s within the collagen meshwork adding structural rigidity to the extracellular matrix of articular cartilage

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Proteoglycan Aggregate

(-) charge

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Water

Most abundant component of articular cartilage

80% concentrated near articular surface

Contains many mobile cations that greatly influence the mechanical and physiochemical behaviors of cartilage, and balance negative charge of PG’s (sodium, calcium)

Essential to health of avascular cartilage (permits movement of gasses, nutrients, and waste products between chondrocytes and surrounding nutrient-rich synovial fluid)

Movement of water (up to 70% under load) important in controlling cartilage mechanical behavior joint lubrication

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Interaction Among Cartilage Components

Collagen and proteoglycans interact to form a porous composite fiber-reinforced organic solid matrix that is swollen with water

Collagen-PG solid matrix and interstitial fluid protect against high levels of stress and strain developing in the ECM when articular cartilage subjected to external loads

Organization of Cartilage

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Biomechanical Loading of Articular Cartilage

Forces at joint surface vary from zero to several times body weight

“Contact” area varies in a complex manner; typically only several square centimeters

Potentially high stress’s

Think of cartilage behavior with load as biphasic (solid component and water)…wet sponge?

Arrangement of Collagen in Articular Cartilage •Superficially: •Tangential orientation of collagen resists shear as joint surfaces move past each other

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Arrangement of Collagen in Articular Cartilage •Middle: •High water content, high PG content •With early load, water moves to joint space and participates in lubrication. • With late load, negative charge of PG molecules begin to repulse each other and offer resistance to compression •Fairly isotropic

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Stress-Strain Curve Uniaxial tensile test: •Constant low strain rate •Dynamic young’s modulus somewhere 40-400MPa •Model does not accommodate fluid flow, or physiologic loading

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Mechanical testing

•Confined compression creep test: is a uniaxial strain test. •Confined chamber so deformation can only occur along axis of loading, •An applied constant stress, •Fluid can escape, •Creep occurs and eventually equilibrium •Experiment is repeated over various stresses and respective strains and aggreate modulus HA is obtained (typically 0.3-1.3 MPa)

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Compression test of cartilage plug (Mow 1977)

•Stress Relaxation •Nonlinear phenomenon

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Shear Stress

High poison’s ratio, thus normal load leads to large lateral displacement relative to bone thus high shear stresses at cartilage/bone interface

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Pure Shear

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Remember: Pure shear is equivalent to a combination of tension and compression applied at +/-45 degrees to the plane of shear

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If shear can be thought of as partially a tensile force and collagen resists tensile forces, then an increase in collagen content should increase resistance to shear:

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Likewise for compression and proteoglycan content

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Less water means less proteoglycan per unit volume? Also a function of ageing

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Creep Test

Constant load Deformation is not instantaneous, as it would be in a single-phase elastic material such as a spring. Displacement of the cartilage is a function of time, since the fluid cannot escape from the matrix instantaneously Initially, the displacement is rapid. This corresponds to a relatively large flow of fluid out of the cartilage. As the rate of displacement slows and the displacement approaches a constant value, the flow of fluid likewise slows. Equilibrium takes several thousand seconds

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Creep Test Biphasic model consideration leads to: Aggregate modulus Modulus

at equilibrium 0.5 to 0.9 MPa (referred to Young’s modulus of cartilage

Permeability Resistance

to flow

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Permeability

Flow velocity proportional to pressure gradient 10-15 to 10-16 m4/Ns If a pressure difference of 210,000 Pa (about the same pressure as in an automobile tire) is applied across a slice of cartilage 1 mm thick, the average fluid velocity will be only 1*10-8 m/s, which is about 100 million times slower than normal walking speed

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As you compress the tissue, you do two things: close the space for water to flow through by compacting tissue, also increase charge density thus slowing flow.

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Putting it all together

As you stand Complex interaction of stress in the cartilage matrix and pressure in the fluid. Cartilage stops itself from “bottoming out” because its permeability decreases with increased strain, and it’s stiffness increases. Caritlage has to be thought of as a dynamic structure (see example 4.2)

Clinical Correlate

Arthritic cartilage has a lower modulus and increased permeability (higher water content, lower proteoglycan content).

This leads to greater and more-rapid deformation than normal.

Theoretically, these changes may influence the metabolic activity of the chondrocytes, which are known to respond to their mechanical environment (mechanotransduction).

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Clinical Correlate

Hypothesis:

Cartilage thought to fail in tension/shear at surface that creates a fissure that propagate

Fact:

Femoral head arthritis far more likely than talus arthritis

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Clinical Correlate

Old cartilage fails earlier than young cartilage

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Lubrication of Articular Cartilage Synovial joints subjected to enormous range of loading conditions Cartilage typically sustains little wear ——————————————————-Implication:

Sophisticated lubrication process required

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Joint Lubrication

Amazing engineering feat

Coefficient of friction of cartilage on cartilage somewhere around 0.001!!!!

Compare to teflon on teflon .04

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Lubrication Processes for Articular Cartilage (High loads) Fluid-film Lubrication

Hydrodynamic Lubrication

(Low loads) Boundary Lubrication

Squeeze-film Lubrication

Arthroplasty

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Boundary Lubrication Synovial fluid constituent responsible for boundry lubrication • glycoprotein – lubricin or • phospholipid – dipalmitoyl phosphatidylcholine ??

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Boundary Lubrication

Surfaces of cartilage protected by a layer of boundary lubricant Direct surface-to-surface contact is prevented Most surface wear eliminated Lubricin (glycoprotein) synovial fluid constituent responsible for boundary lubricant

Absorbed as monolayer to each articular surface Able to carry loads (normal forces) and reduce friction

Independent of physical properties of lubricant (e.g., viscosity) and bearing material (e.g., stiffness) Primarily depends on chemical properties of lubricant Functions under high loads at low relative velocities, preventing direct contact between surfaces

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Modes of Mixed Lubrication Combination of fluid-film and boundary lubrication

Temporal coexistence of fluid-film and boundary lubrication at spatially distinct locations Joint surface load sustained by fluid-film and boundary lubrication Most friction in boundary lubricated areas; most load supported by fluid-film

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Lubrication Processes for Articular Cartilage Fluid-film Lubrication Hydrodynamic Lubrication

Boundary Lubrication

Squeeze-film Lubrication

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Fluid-film Lubrication Thin film of lubricant separates bearing surfaces Load on bearing surfaces supported by pressure developed in fluid-film Lubrication characteristics determined by lubricant’s properties

Rheological

properties Viscosity and elasticity Film geometry Shape of gap between surfaces Speed of relative motion of two surfaces

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Lubrication Processes for Articular Cartilage Fluid-film Lubrication

Hydrodynamic Lubrication

Boundary Lubrication

Squeeze-film Lubrication

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Hydrodynamic Lubrication Occurs when 2 nonparallel rigid bearing surfaces lubricated by a fluid-film that moves tangentially with respect to each other Wedge of converging fluid formed Lifting pressure generated in wedge by fluid viscosity as the bearing motion drags fluid into gap

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Schematic of Hydrodynamic Lubrication

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Lubrication Processes for Articular Cartilage Fluid-film Lubrication

Hydrodynamic Lubrication

Boundary Lubrication

Squeeze-film Lubrication

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Squeeze-film Lubrication

Occurs when weight bearing surfaces move perpendicularly toward each other Wedge of converging fluid formed Pressure in fluid-film result of viscous resistance of fluid that acts to impede its escape from the gap Sufficient to carry high loads for short durations (eventually contact between asperities in bearing surfaces)

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Schematic of Hydrodynamic Lubrication

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Schematic of Squeeze-film Lubrication

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Articular Cartilage Asperities and Lubrication Articular cartilage not perfectly smooth; asperities Fluid film lubrication in regions of cartilage non-contact Boundary lubricant (lubricin) in areas of asperities Low rates of interfacial wear suggests that asperity contact rarely occurs in articular cartilage

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Asperities in Articular Cartilage

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Lubrication Processes for Articular Cartilage Fluid-film Lubrication

Hydrodynamic Lubrication

Boundary Lubrication

Squeeze-film Lubrication

Mixed Lubrication

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Modes of Mixed Lubrication 2. Boosted lubrication

Shift of fluid-film to boundary lubrication with time over the same location Articular surfaces protected during loading by ultrafiltration of synovial through the collagen-PG matrix

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Modes of Mixed Lubrication 2. Boosted lubrication (continued)

Solvent component of synovial fluid passes into the articular cartilage during squeeze-film action yielding a concentrated gel of HA protein complex that coats and lubricates the surfaces As articular surfaces approach each other, difficult for HA macromolecules to escape from gap between surfaces

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Variation of Lubrication Processes for Articular Cartilage Elastohydrodynamic Lubrication - associated with deformable articular cartilage - pressure from fluid-film deforms surfaces Fluid-film Lubrication

Hydrodynamic Lubrication

Boundary Lubrication

Squeeze-film Lubrication

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Comparison of Hydrodynamic and Squeeze-film Lubrication under Rigid and Elastodynamic Conditions

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Elastohydrodynamic Lubrication

Beneficial increase in surface areas Lubricant

escapes less rapidly from between the bearing surfaces Longer lasting lubricant film generated Stress of articulation lower and more sustainable

Elastohydrodynamic lubrication greatly increases load bearing capacity

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Dynamic Relationship between Vertical Load and Hip Joint Lubrication

Support phase

Swing phase

Support phase

Swing phase

•Initial load on hip at heel contact likely supported by hydrodynamic lubrication

•Small vertical load on hip articular cartilage supported by hydrodynamic lubrication

•As load continues, fluid is squeezed between articular surfaces and is supported more by squeeze-film lubrication

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Dynamic Relationship between Vertical Load and Hip Joint Lubrication Time = start •Load on hip supported by squeeze-film lubrication

Time = 3 minutes •Over time fluid-film may be eliminated and surfaceto-surface contact may occur

time = start

time = 3 minutes

•Surfaces protected by thin layer of ultrafiltrated synovial gel (boosted lubrication) or by the adsorbed lubricin monolayer (boundary lubrication)

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Two Types of Wear of Articular Cartilage

Interfacial – due to interaction between bearing surfaces

Adhesion wear – surface fragments from bearing surfaces in contact with each other adhere and are torn away Abrasion wear – soft material is scraped by hard material (opposing surface or loose particles)

=========================================== Effective joint lubricating system makes interfacial wear unlikely under normal articular cartilage conditions Interfacial wear may take place in an impaired or degenerated synovial joint

=========================================== Fatigue wear

due to accumulation of microscopic damage within the bearing material under repetitive stress; not from surface-to-surface contact Bearing surface failure from repeated application of high loads over short period of time or repetition of low loads over long period of time

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Potential Methods for Articular Cartilage Degeneration Magnitude of imposed stresses Total number of sustained stress peaks Change in the collagen-PG matrix Change in mechanical properties of the tissue

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Articular Surface of Cartilage

Normal intact surface

Eroded articular surface

Vertical split in articular surface

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