Articular Cartilage Ori

7/30/2019 Articular Cartilage Ori

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ARTICULAR CARTILAGE AND HEALINGBASIC SCIENCE

VASU NALLALUTHAN

SPV: DR. BADRUL


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Gross anatomy & Type of cartilage1

Cartilage elastic, fibro-cartilage, fibro-elasticand hyaline cartilage.

Articular cartilage type of hyaline cartilagethat cover gliding surfacesof synovial joint.

Highly specialized tissue2

Unique mechanical behavior2

Poor regenerative capacities2


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Embryology of Cartilage1

Cartilage arises from mesenchyme. Some mesenchyme cells aggregate to form a

blastema(5/52 gestational age).

The cells of blastema begin to secrete cartilage

matrix chondroblasts. Further development

Extracellular matrix that produced gradually pushesthe cells apart cells encased in tough and

specialized matrix (chondrocytes). The mesenchymal tissue surround the blastema

membrane perichondrium.


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Anatomy of articular (Hyaline) Cartilage1

Aneural, avascular and alymphatic structure.

Consists: Chondrocytes

Extracellular matrix ~ dense primarily of water, collagen, and proteoglycan.

Low metabolic activity2

Chondrocytes form only15% volume of the articular cartilage.

receive nutrition via diffusion through the matrix.

very specialized cells

responsible for synthesizing and maintaining the matrixinfrastructure.


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Anatomy of articular (Hyaline) Cartilage

Matrix pH is 7.4, changes can easily disruptthe highly specialized matrix infrastructure.

Chondrocyte metabolism for the maintenanceof a stable and abundant extracellular matrix.

Mixture of fluid and matrix provides hyalinecartilage with viscoelasticand mechanicalproperties for efficient load distribution.


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Composition of articular cartilage

Water1,2: 65 80%

80% superficial zone; 65% deep zones

Allows load-dependent (hydraulic pressure) deformation of thecartilage.

Viscoelastic properties2

Its time dependence, reversible deformability, and ability to dissipate load.

It provides nutrition and medium for lubrication, creating a low-friction gliding surface.

majority of water within the interstitial intrafibrillar space (by

collagenproteoglycan solid matrix)2

Related to Donnar osmotic pressure fixedve charges onproteoglycan


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Collagen1,2

: 1020% of wet weight of the articular cartilage.

triple helix structure

Type II collagen forms the principal component (90

95%) of the macrofibrilar framework provides atensile strength to the articular cartilage.

In solid matrix collagen line up in staggered end-to-end and side-to-side fashion to form fibrils with holes

and overlaps. Intra-and intermolecular cross linking fibrils

stabilize the matrix.


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Proteoglycans1,2

: 1020% wet weight protein polysaccharide molecules

provide compressive strength to articularcartilage.

Two major classes in articular cartilage

LARGEaggregating proteoglycan monomers oraggrecans

SMALL proteoglycans including decorin, biglycanand fibromodulin.

They are produced inside the chondrocytes andsecreted in the matrix.


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Aggregan

long protein core with up to 100 chondroitin sulfate and 50 keratan sulfateglycoaminoglycan chains.

Bind via a link protein on the protein core to a hyaluronate molecule.

Hyaluronate molecules form a backbone with palisading aggreganmolecules macromolecular complex proteoglycan aggregate.

The interaction between the proteoglycan molecules and collagenfibrils creates a fiber-reinforced composite solid matrix.

The proteoglycans are entangled and compacted within thecollagen interfibrillar space, which helps to maintain a porous-

permeable solid matrix and determines the movement of the fluid

phase of the matrix


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Proteoglycan aggregate and aggrecan molecule2

Source: Bhosale AM and Richarson JB. (2008). Articular cartilage: structure, injuries and review of management.British

Medical Bulletin; 87:77-95


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Type of collagen and its f(x)2

Source: Bhosale AM and Richarson JB. (2008). Articular cartilage: structure, injuries and review of management. British



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Ultra-structure of articular cartilage1

Source: Bhosale AM and Richarson JB. (2008). Articular cartilage: structure, injuries and review of management. British



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Ultra-structure of articular cartilage1

Chondrocytes organize the collagen,proteoglycans and non-collagenous proteins unique and highly specialized tissue, suitable tocarry out functions.

Morphologically 4 named zones, from top tobottom

1. Superficial zone

2. Transitional zone

3. Middle (radial) or deep zone and

4. Calcified cartilage zone


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Structure of Cartilage2


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Articulating Surface (Superficial zone)1

The thinnest layer, composed of flattened ellipsoid cells. Lie parallel to the joint surface

The fibrils provide greatest tensile and resist shear strength2

Covered by a thin film of synovial fluid laminasplendens or lubricin. Protein responsible for smooth gliding surface2

Chondrocytes synthesize high concentration of collagen +low concentration of proteoglycans highest water contentzone.

Also as a filter for the large macromolecules protecting cartilage from synovial tissue immune

system. Disruption of this zone alters the mechanical

development of osteoarthritis. A.k.a tangential zone


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Transitional zone1,2

Cell density lower, with predominantlyspheroid-shaped cells, embedded in abundantextracellular matrix.

Large diameter collagen fibres randomly

arranged in this zone. Proteoglycan aggrecan concentration is higher

in this zone.


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Middle (radial)/ Deep zone1,2

40% to 60% of articular cartilage volume Higher compressive modulus than superficial

zone

Collagen fibrils are thicker fibers, packed

loosely, and aligned obliquely to the surface.

Chondrocytes are arranged perpendicular to thesurface and are spheroidal in shape.

Highest concentration of proteoglycans.

The cell density is lowest in this zone.


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Calcified cartilage zone1,2

Mineralized zone contains small volume of cells embedded in a calcified

matrix a very low metabolic activity. Chondrocytes hypertrophic phenotype and synthesize Type X collagen,

responsible for providing important structural integrity and provide a shockabsorber along with the subchondral bone.

The visible border between the 3rd and 4th zones is termed as tidemark,

which has a special affinity for basic dyes, such as toluidine blue. This zone provides an important transition to the less resilient subchondral bone.

This zone was considered as an inactive zone

Chondrocytes in this zone were able to incorporate sulphate into pericellular and territorialmatrix.

Following injury, the metabolic activity in this zone becomes temporarilyimpaired.

Matrix zones is organized in three different zones in the cartilage

1. Pericellular

2. Territorial

3. Inter-territorial


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Calcified cartilage zone

Pericellular matrix : Thin rim of matrix-organized issue in close contact with the cell membrane (2-m m wide).

Rich in proteoglycans and non-collagenous proteins, like cell membrane-associatedmolecule anchorin CII, and decorin.

Contains non-fibrillar collage, made of Type VI collagen.

Territorial matrix Surrounds pericellular region and is present throughout the cartilage.

Surrounds individual chondrocytes or a cluster of chondrocytes including their pericellularmatrix.

In the radial zone, it surrounds each column of chondrocytes.

Collagen fibrils organized in a criss-cross forming a fibrillar basket surrounding clusteredbunch of chondrocytes, protecting them from mechanical impacts.

Inter-territorial matrix

Most of the volume of all types of matrices + largest diameter of collagen fibrils. Fibres oriented differently in different zones, depending on the requirement, viz. parallel in

the superficial zone and perpendicular in the radial zone.

Special features to identified formation of aggregates of proteoglycan molecules


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ORGANIZATION OF ARTICULAR CARTILAGE3


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f(x)of hyaline articular cartilage1,2

1. Provides a low-friction gliding surface.2. Acts as a shock absorber.

3. Minimizes peak pressureson the subchondralbone.

4. compressive strength

5. Wear-resistantunder normal circumstances


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f(x)of the matrix1

1. Protectsthe chondrocytes- mechanical loading,

maintain their phenotype.

2. Storage cytokines and growth factors forchondrocytes.

3. Determines the type, concentration and rate of

diffusion of the nutrientsto chondrocytes.

4. Acts as a signal transducerfor the cells.

Matrix deformation produces mechanical, electrical andchemical signals, affecting the functions of chondrocytes.

Matrix recording a loading history of the articular cartilage.


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Natural Hx of Chondral Injuries1

Articular cartilage lesions most commonly 4th

decade of life Full thickness lesions common in young adults

3rd decades, following acute traumatic injuries. Repetitive minor trauma and major overt injuries

Typical symptoms of chondral injury are similar tomeniscus tear, like swelling, local pain, locking,pseudo-locking and catching.

Outerbridge has classified these focal chondraldefects into different stages, based on the severity

of the defect. Large focal defects untreated premature end-

stage arthritis.


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Natural Hx of Chondral Injuries

Structurallesion

LocalBleeding

Formation ofblood clot

Localized

spontaneousrepair

activity

Direct

ossification@ bony

surface


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Partial thickness vs Full thickness

Damage to the cells and matrixcomponents limited to superficialarticular involvement.

Characterized by proteoglycan(PG) concentration and hydration.

in cartilage stiffness and an in

hydraulic permeability leading togreater loads transmitted to thecollagen-PG matrix, whichincreases ECM damage.

Breakdown of the ECM may lead togreater force transmitted to the

underlying bone that eventuallyleads to bone remodeling.

By visible mechanical disruption limitedto articular cartilage.

Characterized as (but not limited to)chondral fissures, flaps, fractures, andchondrocyte damage.

Lack of vascular integration, and lack ofmigration, of mesenchymal stem cells tothe damaged area limits the repair of thistype of injury.

Mild repair occurs as chondrocytes startproliferating and synthesizing additionalECM

Response is short lived, and defectsremain only partially healed.

Normal articular cartilage that is adjacentto the damaged site may undergoadditional loading forces pre-disposing itto degeneration over time.

Partial Full


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Partial thickness vs Full thickness


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Classification3

OUTERBRIDGECLASSIFICATION

OF CHONDRAL INJURIES

MODIFIED INTERNATIONAL

CARTILAGE REPAIR SOCIETY

CLASSIFICATION

SYSTEM FOR CHONDRAL

INJURY


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Management

The most commonly tx for end-stage kneeosteoarthritis prosthetic replacement of thearticular surface (a.k.a total knee arthroplasty).

Suitablefor the elderly people (> than 60years of age,

with a sedentary life style) Pt < 45 yearsof age not ideal candidatesfor TKR


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Repair & Regeneration of chondral Injuries1

Repair restoration of a damaged articular surface with a

neocartilage tissue, which resembles to the native cartilage,but does not necessarily duplicate its structure, compositionand function.

Regeneration formation of tissue, indistinguishable fromthe native articular cartilage.

A typical tissue response to injury follows a cascade ofnecrosis, inflammation, repair and scar remodelling.

Vascular phase of this cascade is the most importantdeterminant of healing. Hyaline cartilage, being avascularstructure, lacks an ability to generate this vital response.

Thus, after any mechanical insult or damage, the intrinsic

reparative ability of cartilage is very low. Healing of the cartilage defect means restoring structural

integrity and function of the damaged tissue.


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Factors a/w repair response1

Depth Of Defect Size of Defect

Age

Trauma

Mechanical malalignment of the joint


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Intervention

Therapeutic interventions without active4

Lavage and Arthroscopy

Shaving

Laser Abrasion/ Laser Chondroplasty

Bone marrow stimulation1 Joint Debridement and Pridie drilling1

Abrasion Chondroplasty4

Microfracture technique4

Spongialization4

Extensive Surgical intervention4,6 Osteotomy1

Distraction of Joint


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Intervention

Therapeutic interventions with active biologics4

Mosaicplasty (Osteochondral Transplantation)1

Perichondrial grafts 1

Periosteal grafts 1

Autologous chondrocyte implantation1 Tissue Engineering4

Matrices

Carbon fibre implants1

Cells in Suspension

Cells in a Matrix-Carrier System


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Intervention


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Different strategies for cartilage repair


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Osteochondral Transfer


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Autologous Chondrocyte implantation


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References

1. Bhosale AM and Richarson JB. (2008). Articular cartilage:

structure, injuries and review of management. British MedicalBulletin; 87:77-952. Pearle AD et al., (2005) Basic Science of Articular Cartilage and

Osteoarthritis.Clinical Sports Medicine; 24: 1-123. Pylawka TK et al. Chapter 30: Articular Cartilage Injuries. Available

at

www.pacificaorthopedics.org/downloads/knee/Articular_Cartilage_Injuries.pdf. Accessed on 14 /06/124. Hunziker E.B., (2001).Articular cartilage repair: basic science and

clinical progress. A review of the current status and prospects.Osteoarthritis and Cartilage 10, 432463.

5. Redman et al. (2005) Current Strategies for Articular Cartilage

Repair. Review of Cartilage Repair . Strategies European Cells andMaterials Vol. 9: pp 23-326. ODriscoll SW. (1998) Current Concepts Review: The Healing and

Regeneration of Articular Cartilage. Journal of Bone and JointSurgery, Incorporated. Vol 80-A:1795 - 1812

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