Orthomech L4 Cartilage

• Hyaline: Found in nose, ribs
• Fibrous: Found in intervertebral discs, meniscus, temporomandibular joint
• Elastic: High in elastin, found in outer ear, epiglottis

• Water and electrolytes
• Matrix: Has collagen II, aggrecan, and other collagens and PGs
• Cells: Chondrocytes (1-10%)

• Triple helix like a biological rope providing tensile strength
• Cross linked for stability
• Arranged into sheets which form arcs
• Immobilises PGs

The most common GAG in cartilage

Negatively charged and aggregates to hyaluronan

• Bear Loads
• Absorb mechanical shock
• Spread load
• Provide joints with excellent friction, lubrication and wear characteristics.

• Diffusion: Through bone and synovial fluid for very small molecules
• Convective transport: Associated with time varying loads for transport of larger solute molecules

• Indentation
• Confined compression
• Unconfined compression

• Compression
• Tension
• Shear
• Time scale
• Viscoelasticity
• Permeability
• Pressure and charge density
• Hydration

Think about a Pr TeCh HyPe ViSh TyCo

 Gives tissue resistance to compression

• Cartilage swells due to two types of pressure:
• Charge-to-charge repulsive force: Exerted by closely packed negatively charged PGs
• Donnan osmotic pressure: Due to high density of fixed negative charge in PGs

• GAGs and PGs have a negative charge
• PGs are immobilised by cartilage
• Counter ions are attracted to cartilage to maintain equillibrium
• This changes the solute concentration between the cartilage and the synovial fluid
• Water is drawn into cartilage by osmotic pressure and causes cartilage to swell

• Negative charges between closely packed PGs leads to repulsive forces between the sub-units and within each sub-units
• Causes tissue to swell further
• Articular cartilage is prestressed

• Superficial tangential zone
• Middle zone
• Deep zone
• Calcified cartilage
• Cancellous bone
• Subchondral bone
• Tide mark
• Articular surface

Compressive stiffness increases as function of total GAG content

Not corellated to collagen content

• No
• Superficial zones are stiffer than middle and deep zones.
• Collagen fibres take the load

As cartilage is compressed its permeability decreases.

Cartilage is biphasic = fluid water + Solid ECM

• It has Rate dependence
• Elastic behaviour
• At rapid loading, now fluid flow
• Stiffens with increasing strain rate

Function of (1/thickness²)

• Combination of flow dependent drag and non flow-dependent, intermolecular friction of collagen/proteoglycan matrix mechanisms.
• 
• 

A mathematical law that is used to experimentally determine the stress strain response

• It is avascular : No haemorrage or injury response
• No inflammatory cells to remove necrotic tissue

• It lacks cells: Lack of undifferentiated cells, only differentiated condrocytes
• Little cell migration
• Limited synthesis of matrix

• Could not describe the known effects of interstitial fluid flow
• Cartilage exudes water when compressed and absorbs fluid when soaked

More successful models

• Biphasic: Two intrinsically incompressible and immicscible phases
• Triphasic: As above but with effects due to charge

• Physicochemical
• chondrocytes sensitive to extracellular osmolarity and pressure is linked to permeability
• Cell deformation: Chondrocyte volume thought to exert strong influence on biosynthetic activity
• Tough to study in vitro though. Chondrocytes repond differently according to the zones in articular cartilage.
• Hydrostaic pressure: Thought to modulate aggrecan biosynthesis through membrane mediated pathways and through chondrocyte response 
• Fluid transport: Fluid flow might regulate chondrocyte metabolism: Accelerates transport of solutes and macromolecules
• Fluid flow can induce shear stress on chondrocytes to accelerate transport of solutes and molecules
• Electromechanical transduction: Non uniform fixed charge density, electric potentials and currents due to deformation of  matrix

Primary: Unknown cause affecting mainly elderly

• Secondary: After joint injury
• Result of obesity or developmental factors.

Primary changes: Cartilage loss, subchondral bone remodelling, osteophyte reformation

Might also affect muscles, synovial capsule and ligaments

• Alteration of cartilage matrix:
• Decreased proteoglycan content
• Increased water content
• Collagen II first unaffected then network may be damaged
• Blood vessels cross tidemark
• Stiffening of subchondral bone.

• Response of chondrocytes:
• Chondrocytes detect damage and proliferate to synthesise matrix (anabolic)
• Matrix metaloproteases degrade matrix molecules (catabolic).
• Nitric oxide released after mechanical stimulus, stimulate expression of NO through interleukin 1
• Reformation depends on balance of anabolic and catabolic

• Stage 3, death of chondrocytes:
• Loss of cartilage
• Subchondral bone thickening
• Osteophyte formation at joint periphery.

Weight loss, exercise drugs, nutrition, glucosamin sufate etc

• Surgery
• Altering mechanics: If OA is on one side shif the load away with a wedge.

Direct cartilage treatment (cleanup) with arthroscopic washout.

Direct cartilage tissue grafting or autologous chondrocyte cell therapy

Last resort: Joint replacement or joint distraction