Rethinking Arthritis

Robert Joseph DPM, PhD

Classically Why Cartilage Is Difficult

to Repair or Regenerate
suppose to look white, shiny & glisening

Avascular
Relatively Acellular
Low Metabolic Activity
Heterogeneous

arthritc cartilage

General Organization of Cartilage

the way it functions
lots of bricks holding everything together

Mortar = Matrix

Bricks= Cells

Chronic Cartilage Degeneration

basically the motor breaks down
bricks break down-cells break down

Mortar Breakdown
Matrix Degradation

Broken Bricks
Cell Death

Catabolism is greater than anabolism thus things break down

synovial fluid-very import in cartilage health

Cartilage Degeneration

Inflammatory
Cytokines

Catabolism

Growth Factors

Anabolism

Cartilage Repair
Chondrocytes are Natural Tuck-pointers
cells are natural tuck pointers takes out bad bricks puts in new ones

Most Tissue Have

More Cells Than
Matrix

2-5 % Chondrocytes
why doesnt it repair itself? a lot of repair is down by
lots of dif cell

A lot of Repair Needs to Be Performed By Few Cells

Relatively Acellular

Cartilage Repair
Text

No Arterioles
Synovial Fluid
chondrocytes only change cells right in
front of them

Subchondral plate
Cartilage is
Avascular

collegen twists & turns like chicken wire; acts like a sponge filled with water

Chrondrocytes Only Repair The

Immediate Vicinity
Pericellular
Territorial
Interterritorial

Fibronectin

Cartilage is a
heterogeneous tissue
Modis L Organize of
Extracellular Matrix 91

Proteoglycan

Superficial Zone

flat cells

round cells

Middle Zone

cells in clusters

Deep Zone

Subchondral Bone

Not All Chondrocytes are the Same

Cartilage is
Heterogeneous

Cartilage is
Heterogeneous
Composition
Thickness
Softness
Subchondral bone stiffness
Mechanics

ankle

Talar Dome

knee
vs

Distal Femur

Talar Dome

Superficial Zone

Middle Zone

Deep Zone

Subchondral Bone

Deep Zone Matrix

Middle Zone Matrix

Chondrocyte
Superficial Zone Matrix

Cartilages Physical Properties

Limit Current Treatment
Therapies

Osteochondral Lesion
MRI

Osteochondral Transplantation
Focal Lesion of Cartilage

Physical Stress Riser

SR-concentration of forces in one concentrated area

A Concentration of Stress in Material

occurs in

Geometric Discontinuities
Cracks
Holes
Sharp Angular Bends

occurs in

Changes in Cross Sectional Area

Points of material property change

Consequence of Stress Raisers

Engineering
Cracks
Material Fatigue
Material Breakdown

Biologic Tissues
Fracture
Tissue Breakdown
Degeneration
-very slow

Osteochondral Transplantation
know/understand this slide

Histologic
Mismatch of
Cartilage
Zones

Stress Riser

Metabolic Stress Raiser

Changes in chondrocyte metabolism that alter
the physical composition of the extracellular
matrix thereby creating a mechanical stress
raiser by altering the deformation
characteristics of cartilage
Mechanical stimulus influences chondrocyte
metabolism
Chondrocyte metabolism influences matrix
mechanics

Metabolic Stress Raisers

Limit cartilages ability to successfully recreate

the natural layers and heterogeneous nature
of cartilage

Autologous Chondrocyte Transplantation

wont line up perfectly; cells will be all over the place(random)
odd mismatch of chondrocytes

Consequences of Stress Raiser

Formation in Cartilage Repair
Fibrocartilage
Biologic Scab

The Horizon of Therapy

get native cells to go where they need to go
strif each cell layer after u take plug out of pt

Scaffold Engineering
Scaffold Delivery Systems
Growth Factors
Multipotent cells
Mesenchymal cells

grow cells on scaffold over & over again

trick cells into behaving like normal cells & trick them
into staying where they really belong

Summary
Unique properties of cartilage make it difficult to
heal:

Avascular
Low cellularity
Slow metabolism
Heterogeneous composition

Stress raiser formation contributes to failure of

several popular treatments of O.C.D.
Physical stress raiser
Metabolic stress raiser

Thank You
Robert Joseph, DPM, PhD
footbiochemistry@hotmail.com