Cartilage, function, structure, mechanics

SUB CRUCE LUMEN - THE UNIVERSITY of ADELAIDE 2009 American College of Rheumatology

Learning Objectives

  • Describe primary mechanical goals of articular cartilage.

  • Describe the structure and composition of articular cartilage.

  • Explain the mechanical behaviour of articular cartilage in terms of biphasic/triphasic nature, heterogeneity and anisotropy.

  • Describe the effect of osteoarthritis on the mechanical behaviour of articular cartilage.

Overview of Joints

Definition

  • Joints are locations at which 2 or more bones make contact.

Types of Synovial Joints

  • Condylar Joints: Example - wrist.

  • Hinge Joints: Example - elbow.

  • Ball & Socket Joints: Example - hip.

  • Saddle Joints: Example - carpometacarpal joint of thumb.

  • Pivot Joints: Example - atlanto-axial.

Structure of Synovial Joints

  • Articular Cavity: Contains synovial fluid.

  • Hyaline (Articular) Cartilage: Layer covers articulating surfaces, optimizes function.

  • Joint Capsule: Composed of inner synovial membrane and outer fibrous membrane.

Major Features and Accessory Structures (Gray’s Anatomy for Students)

  • Important for stability and function of joints.

Characteristics of Cartilage

General Properties

  • Connective tissue that is dense, translucent, and white.

  • Lacks nerve endings and blood vessels.

  • Possesses very low cellular density, which is the lowest among any tissue.

Types of Cartilage

  1. Hyaline Cartilage

    • Composition: Homogenous matrix with Type II collagen fibres oriented along lines of force.

    • Locations: Articular joints, cartilage of nose, larynx, sternum, ribs, and tracheal rings.

  2. Fibrocartilage

    • Composition: Type I collagen and extracellular matrix.

    • Locations: Menisci, labra, intervertebral discs (annulus fibrosus).

  3. Elastic Cartilage

    • Contains elastic fibres.

    • Locations: Ears and epiglottis.

Mechanical Functions of Articular Cartilage

  • Distributes joint loads over a larger area to reduce contact stress which ranges between 2−11extMPa2-11 ext{ MPa}.

  • Allows for relative motion of joint surfaces with low friction and wear.

  • Optimized structure and composition facilitate these functions.

  • Thickness of articular cartilage varies from 1−6extmm1-6 ext{ mm}.

Part 1: Composition & Structure

Composition of Articular Cartilage

  • Triphasic Nature:

    1. Porous Matrix

    • Organic matrix consists of 15-22 ext{% w/w}, characterized by a dense network of collagen fibrils, primarily Type II.

    • Contains a proteoglycan solution/gel, comprising 4-7 ext{% w/w}.

    1. Water

    • Constitutes 60-85 ext{% w/w} of cartilage, along with inorganic salts and other proteins.

    1. Charged Molecules and Ions

    • Ions such as Na+, K+, Ca2+, and Cl- contribute to the unique properties of the cartilage matrix.

Collagen (Type II)

  • Diameter of collagen fibrils varies significantly:

    • 0.01−0.025extμm0.01-0.025 ext{ μm} in the superficial and middle regions.

    • 0.3extμm0.3 ext{ μm} in the deep zone.

  • Type II collagen has a smaller diameter than Type I.

Proteoglycans

  • Structure: Large protein-polysaccharide molecules consisting of a protein core with one or more glycosaminoglycans (GAGs) covalently bonded.

  • Predominant type in cartilage: Aggrecan (80-90% of total proteoglycan content).

    • Overall Structure of Aggrecan: Core protein + chondroitin sulfate and keratan sulfate chains.

    • Aggrecan interacts with hyaluronan (HA) through link proteins, forming large aggregates.

GAG Sidechains

  • GAGs exhibit negative charges from sulfate and carboxyl groups, leading to charge-charge repulsion.

  • Counteracting ions, like Na+, create swelling pressure of approximately 0.25extMPa0.25 ext{ MPa}.

  • Equilibrium compressive stiffness of the extracellular matrix (ECM) is between 0.5−1.0extMPa0.5-1.0 ext{ MPa}.

Collagen-Proteoglycan Interactions

  • The ECM consists of collagen and proteoglycans interacting through friction.

  • The swelling pressure generated by fixed charge density inflates the collagen network, allowing it to resist tensile and shear loads.

Interstitial Water

  • Approximately 30 ext{%} of the interstitial water is located in the intrafibrillar spaces of collagen.

  • Changes in water content influence mechanical properties, swelling, and fluid-transport properties, which are driven by:

    • Concentration of proteoglycans (swelling pressure from fixed charge density).

    • Organization of the collagen network.

    • Strength and stiffness properties of the network.

Cellular Component

  • Chondrocytes: Form less than 10 ext{%} of tissue volume; They are responsible for manufacturing, secreting, and maintaining the organic components of the ECM.

  • Chondrocytes are embedded in the matrix, receiving nutrients and metabolites through diffusion and rarely divide.

Zones of Cartilage

  • Superficial Tangential Zone (10-20%):

    • Composed of 75-80% water.

    • Contains 85% dry weight collagen with the lowest aggrecan content.

    • Collagen fibers are of finest diameter, densely arranged parallel to the surface, providing high tensile strength and resistance to shear forces.

  • Middle Zone (40-60%):

    • Features decreased collagen content.

    • Increased fiber diameter and loose packing of fibers.

    • Contains the maximum amount of aggrecan.

    • Water content progressively decreases with depth.

  • Deep Zone (30%):

    • Exhibits large bundles of collagen fibers that are radially oriented and equal to the perpendicular structure of the articular surface.

    • Contains the highest collagen content and is anchored to subchondral bone by inserting into the calcified cartilage layer through a tide-mark.

Illustration of Cartilage Zones

  • Collagen fibrils serve as a crucial structural framework throughout various zones of articular cartilage, providing support and stability to chondrocytes and proteoglycan aggregates.

Part 2: Mechanics

Mechanical Behaviour of Cartilage

  • Cartilage is characterized as anisotropic in tensile strength owing to the arrangement of collagen fibers across different zones, including cross-link density and collagen-proteoglycan interactions.

  • Heterogeneity: Exhibits varied properties due to its multi-zonal structure.

  • Poroelastic Solid: Consists of three factors affecting its mechanics:

    1. Intrinsic, flow-independent behavior of the collagen-proteoglycan matrix.

    2. Flow of interstitial fluid through the matrix, along with fluid resistance.

    3. The ionic phase ultimately leads to swelling that resists fluid flow.

Strength Properties

  • Tensile stiffness and strength primarily provided by collagen fibrils.

  • Compressive stiffness is a result of the collagen network restraining the swelling pressure of the proteoglycans.

Models of Cartilage Mechanics

  1. Isotropic, Linear Elastic Model: Excludes creep and stress relaxation, appropriate for specific physiological situations.

  2. Spring-Dashpot Models: Account for creep and stress relaxation without fluid flow consideration.

  3. Biphasic Model (Mow et al., 1980): Encompasses viscoelastic properties and fluid mechanics in assessment.

Biphasic Model Overview

  • Comprised of:

    • Two Incompressible Phases:

    • Fluid phase.

    • Porous, permeable solid phase.

  • The viscoelastic behavior in compression correlates with interstitial fluid flow and frictional drag effects, while shear viscoelastic behavior arises mainly from the movement of collagen and proteoglycans.

  • Permeability declines as load increases, leading to closing of pores and a rise in fixed charge density.

Creep and Compression

Confined Compression Loading

  • Time taken to reach creep equilibrium is inversely proportional to the square of tissue thickness, typically taking 4-16 hours for cartilage that is 2-4 mm thick.

Aggregate Modulus

  • Calculated where aggregate modulus is defined as:
    extAggregateModulus=racextequilibriumstressextequilibriumstrainext{Aggregate Modulus} = rac{ ext{equilibrium stress}}{ ext{equilibrium strain}}

  • Typical values range from 0.3–1.3extMPa0.3 – 1.3 ext{ MPa}.

Permeability of Cartilage

  • Articular cartilage is roughly 80% porous.

  • Permeability quantifies the resistive force required for fluid flow at specified speeds, influenced by the interactions between interstitial fluid and pore walls.

  • Pores are generally about 6extnm6 ext{ nm} in diameter, targeting molecular sizes.

Cartilage in Tension

  • Conducting equilibrium tensile measurements involves low strain rates which negate biphasic fluid flow effects to focus solely on the collagen-proteoglycan matrix response, yielding strains of less than 15%, with EE values between 5−10extMPa5-10 ext{ MPa}.

Part 3: Degeneration

Cartilage Degeneration Mechanisms

  • Wear Types in Cartilage:

    1. Adhesive/Abrasive Wear: Unlikely due to effective surface lubrication preventing separation.

    2. Fatigue: Repetitive mechanical stress leads to micro-damage, disrupting the collagen-proteoglycan matrix and causing proteoglycan “washout.”

    3. Impact Loading: Occurs without stress relaxation, leading to fibrillations and deep fissures in the cartilage network.

Osteoarthritis (OA)

  • Defined as a family of diseases where both cartilage and surrounding tissues pathologically respond to environmental factors, notably mechanical loading.

    • Physical activity in healthy, asymptomatic individuals has been shown to offer biochemical and biomechanical protection against:

    • Cartilage thinning.

    • Development of cartilage defects.

    • Bone marrow lesions.

Biomechanical Risk Factors for OA Development

  • Obesity: Increases joint stress.

  • Trauma: Leading to injury.

  • Joint Destabilisation: Affects cartilage function.

Diagnostic Imaging Techniques in OA

  • Magnetic Resonance Imaging (MRI) and High-Speed Dual-Fluoroscopy tools facilitate measurement of cartilage deformation during various activities.

  • Cartilage strains are dependent on anatomical location within the joint as well as specific activities undertaken.

  • Strain accumulation occurs throughout the day with recovery taking place during the night, showcasing the viscoelasticity of cartilage.

Histological Changes in OA - OARSI System Classification

  • Grade 0: Surface intact; cartilage morphology appears normal.

  • Grade 1: Surface intact; exhibits superficial fibrillation, edema or cell death/proliferation.

  • Grade 2: Surface shows discontinuity.

  • Grade 3: Presence of vertical fissures.

  • Grade 4: Notable erosion.

  • Grade 5: Denuded surfaces.

Human Femoral Head Imaging Cases

  • A comparison of a 79-year-old with no marked degeneration against a 69-year-old with significant cartilage loss, showing areas of total cartilage loss, termed eburnated bone.

Advanced OA Effects on Subchondral Bone

  • Notable findings include eburnated bone and subchondral bone cysts, reflecting advanced degenerative changes.

Model of OA Pathogenesis Including Bone

  • Healthy knee showcases optimized subchondral bone with an even distribution of trabecular rods, positively supporting cartilage functionality.

  • Early-stage OA demonstrates cartilage that appears intact but experiences abnormal bone resorption due to mechanical stress; leading to fewer supporting trabeculae.

  • Advanced stages reflect microstructural changes which disrupt regular cartilage support, contributing to local stress concentrations and further cartilage degradation.

Osteochondral Changes with OA

  • Changes such as tide mark duplication, increased neoangiogenesis (formation of new blood vessels), and nerve growth indicate advanced pathology.

  • Late-stage manifestations include decreased bone mineral density, hypertrophy of chondrocytes, fissures, and increased bone volume.

Summary

  • Function of articular cartilage in diarthrodial joints is critical for distributing load (reducing stress) and providing a low-friction surface for joint movement.

  • The biomechanics of cartilage can be elucidated through biphasic or triphasic models, highlighting how material properties as well as fluid interaction resonate with its compressive behavior.

  • Damage to cartilage disrupts interstitial fluid balance, ultimately compromising load-bearing capacity.