Lecture 4 - Cartilage Flashcards
Hyaline / Articular Cartilage + composition
Found
- joint surfaces, nose, ribs
Constituents
- water + electrolytes (68-85% wet weight)
- matrix: collagen II (10-20%), PG (aggrecan, 5-10%)
- cells = chondrocytes (1-10% vol)
Elastic Cartilage
‘Yellow cartilage’
Found
- epiglottis, outer ear, eustachian tube
- high in elastin
Fibrocartilage
Found
- IVD, meniscus
Collagen structure and function
- triple helix - tensile strength
- crosslinks - stability
- sheets form arcs (extend from deep zone)
Function:
- immobilise PGs
- resist tension
Proteoglycans
Structure:
- core protein (hyaluronan) + covalently attached sugars (GAGs) (aggrecan)
Function:
- negatively charged - repel each other –> compressive strength
- cartilage swells: repulsive forces + osmotic pressure
Mechanism:
- Negative PGs - restrained by cartilage
- counter ions into cartilage –> maintain electrostatic equilibrium
- difference in solute conc between cartilage + synovial fluid
- osmotic pressure draws water in –> swells
Chondrocyte roles
- PG synthesis, modification, organisation
- Collagen synthesis & secretion
- matrix degradation & turnover –> controlled by cytokines, growth factors + proteases
Articular cartilage structure
Superficial:
- high collagen density // to surface
- low PG density
- high chondrocyte density + elongated
- high water content (80%)
Middle:
- mid collagen density, unorganised
- mid PG density
- mid chondrocyte density + spherical
- mid water
Deep:
- mid density collagen |_ to surface (woven)
- high PG
- low chondrocyte density + spherical in columns
- low water (65%)
Tidemark:
- calcified cartilage
Cartilage nutrition
Diffusion: - synovial fluid / bone - v. small molecules - slow diffusion rates Convective: - larger molecules - compressed into cartilage from synovial fluid
Cartilage function
- pre-stressed material
- spread loads (deform –> contact area increases + stress decreases)
- absorb mechanical shock
- friction lubrication
Factors affecting mechanical properties of articular cartilage (7)
- compression
- tension
- shear
- time-scale
- permeability
- pressure + charge density
- hydration
Mechanical behaviour 1 - Compression
- stiffness increases as function of GAG content
- equilibrium modulus, Ha = 0.1-2MPa
- highly loaded regions = stiffer in compression and higher PG content
Mechanical behaviour 2 - Tension
- collagen fibres take load
- E tension = 5-50MPa
- superficial zone stiffer
Mechanical behaviour 3 - Shear Loading
- from joint motion
- no volumetric change so no fluid flow
- collagen content related
- dynamic shear mod, G = 0.2-2.5MPa
- rapid loading –> differences in compliance between bone and cartilage –> high shear stress at cartilage-bone boundary
Mechanical behaviour 4 - Time Effects
- biphasic cartilage (water fluid + ECM solid)
- rate-dependent behaviour
- stiffen with increasing strain rate (rapid loading, no fluid flow)
- viscoelastic (slower loading rates, fluid flow)
- creep + stress relaxation –> flow dependent and non-flow dependent mechanisms
Mechanical behaviour 5 - Permeability
- cartilage permeability v low
- varies by zone (lowest in deep)
- varies with deformation (compressed –> permeability decreases)
- compressed –> porosity decreases & density negative charges increases –> harder to squeeze more fluid out
Mechanical behaviour 6 - Pressure & Charge Density
Compression –> forces -ve charges closer + forces water out with dissolved +ve ions
Mechanical behaviour 7 - Hydration
Water content increases –> cartilage becomes less stiff and more permeable
Osteoarthritic cartilage has more water
Constitutive models for cartilage
Simplest: - isotropic, linearly elastic (generalised hooke's law) Viscoelastic: - springs and dashpots Most successful: - biphasic, triphasic
Biophysical factors evoked by mechanical loading of articular cartilage:
- Physiochemical effects
- chondrocytes sensitive to extracellular osmolarity - Cell deformation
- chondrocyte volume - strong influence on biosynthetic activity - Hydrostatic pressure
- modulate aggrecan biosynthesis - Fluid transport
- Chondrocyte metabolism regulated by interstitial fluid flow
- shear stress on chondrocyte –> aggrecan synthesis - Electromechanical transduction
- deformation –> FCD, electric potentials, currents
Effects of motion and loading:
- loading –> maintain healthy cartilage (increased cartilage matrix synthesis)
- immobilisation –> degeneration (loss PGs, thinning, less stiffness)
- too much loading –> degeneration
Cartilage repair problems:
- low blood supply
- lack of cells (only differentiated chondrocytes)
Osteoarthritis:
What is it?
What is the difference between primary and secondary?
What are symptoms?
- degradation of weight-bearing joints (subchondral bone & articular cartilage)
- primary: spontaneous
- secondary: post-traumatic
- £5.7bn/yr
Symptoms:
- pain
- stiffness
- loss of ROM
Osteoarthritis risk factors
- genetic
- environmental
age (>65)
female
obesity
high bone density - biomechanical (joint injury + misalignment)
Progression of OA
- Alteration of cartilage matrix
- fibrillation, delamination, tears/cracks
- less PG
- more water
- collagen II network damaged
- blood vessels cross tidemark
- subchondral bone stiffens - Chondrocyte response
- detect damage (osmolarity, charge density, strain)
- proliferate + synthesise matrix
- Matrix metalloproteases (MMPs) degrade matrix
- synthesis > degradation - Decline in chondrocyte response
- death
- loss cartilage
- subchondral bone thickening
- osteophyte formation
Treatment: Non-surgical and surgical
- weight loss
- exercise + stretching
- drugs
- supplements
Surgery
- osteomy: wedge taken out of bone - shifts load away from OA region
- arthroscopic washout - cleanup / debridement
- tissue grafting / mosaicplasty
- ACI (fibrocartilage)
- microfracture
- joint replacement
- joint fusion (last resort)
Why the composition and structure of cartilage combine to make it a viscoelastic material
- Cartilage is biphasic, consisting of a solid phase – collagen and proteoglycans – and a fluid phase – water and dissolved electrolytes.
- The pores in the solid phase are very small, making it difficult for the fluid to flow.
- Thus, with rapid loading there is no fluid flow, resulting in increasing stiffness. As cartilage is compressed the permeability decreases and the density of negative charges increases, both increasing stiffness.
Indentation - Cartilage Testing
Involves the use of a small diameter indenter on a much larger sample of
cartilage still attached to subchondral bone. The benefit of this is maintenance of the
cartilage/bone interface, but the drawback is the need for a large section of articular surface
and underlying bone.
Unconfined Compression - Cartilage Testing
Is compression of a plug of isolated cartilage between two
smooth metallic platens. This approach will provide the properties of the solid constituents of
cartilage, but the effects of fluid flow are lost.
Confined Compression - Cartilage Testing
Involves placing a plug of cartilage in a confining chamber and
compressing it with a permeable piston. This enables fluid flow effects to be included and
can be done when a large section of cartilage is not available.
Biphasic Model
Consists of two incompressible and immiscible phases (solid and fluid)
Triphasic Model
Similar to Biphasic but with effects due to charge.
