INFLAMMATION,

WOUND HEALING AND

FOREIGN BODY
RESPONSE
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GENERAL
 Various mechanisms are activated to maintain homeostasis

in blood and tissues after implantation of a device.

 Host reaction varies with:

 Type of tissues

 Organ

 Species

 Extent of injury

 Implantation procedure
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 INFLAMMATION
Inflammation: swelling, redness, heat, and pain produced in an

area of the body as a reaction to vascular living tissue injury or

infection
◦ Injury may be due to injection, insertion or surgery performed

for implantation of a device (biomaterial)

The inflammatory response is the early step in wound healing

process

Inflammation serves to contain , neutralize, dilute or stop

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 Inflammation starts a series of events that may heal and repair

the implant site through replacement of injured tissue by

regeneration of parenchymal cells, formation of scar tissue, or a
combination of both.

 After injury:

 Vascular flow, caliber and permeability change

 Fluid, proteins and blood cells escape from the vascular system into the

injured tissue (exudation).

 Changes are induced in blood and its components , cellular events occur

and characterize the cellular response

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 Initial inflammatory response is activated after injury

to vascular tissues due to implantation

 Blood and its components are involved and this
activates coagulation system, complement system,
fibrinolytic system etc.

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Cell types, dominating the inflammatory response

differ according to the age of the injury

 For the first few days, Neutrophils are the most activated cells

 Monocytes replace neutrophils in coming days. Emigration of

monocytes may continue for weeks depending on the injury,

implanted biomaterial (activation of chemotactic factors
depends on these)
 Monocytes differentiate into macrophages after emigration

from vasculature, and they live for several months

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EVENTS FOLLOWING IMPLANTATION

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 IMPORTANT
 The size, shape, chemical and physical properties of
biomaterial is mostly responsible for variations in the
intensity and duration of inflammatory process.

 Injury initiates the inflammatory response, but chemicals

released from cells, injured tissue and plasma mediate the

response

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 MEDIATORS
1. Different mediator systems interact and provide a system
of checks and balances for their functions

2. Chemical mediators are quickly inactivated or destroyed

at the implant site

3. Generally the lysosomal proteases and O2 derived free

radicals produce significant damage or injury

4. Chemical mediators play a role in degradation of

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biomaterials
 ACUTE INFLAMMATION (AI)
 Inflammation of duration from minutes to days depending on injury

 Accumulation of leukocytes is the most important feature of inflammatory

response.

 Leukocytes engulf and degrade bacteria, immune complexes, and the

debris of necrotic cells.

 Leukocytes also prolong inflammation and induce tissue damage by

releasing enzymes, chemical mediators and toxic oxygen radicals.

 During AI exudation of fluid and plasma proteins and emigration of

leukocytes occur (HOW??). 13

 SEQUENCE OF LEUKOCYTE EVENTS
 Margination

 Pavementing

 Emigration

 Chemotaxis

 Phagocytosis and synthesis of biochemical mediators

 Intracellular degradation

 Extracellular release of leukocyte products 14

 MARGINATION
 Slowing of flow occurs due to increased vascular

permeability
 WBCs:

 fall out of the central column

 Tumble slowly and roll along the endothelium venules

 Rest at some point where they adhere

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 PAVEMENTING
 Endothelium appears to be essentially lined by WBCs

 Chemical mediators (histamine, thrombin, Platelet activating factor PAF

stimulate the redistribution of P-selectin from intracellular granules to

the cell surface.(happens early in infl process)

 Other chemical mediators (TNF & IL-1 and chemokines) secreted by

resident macrophages, mast cells and endothelial cells as a response to

injury. They induce post capillary venule to express adhesion molecules.
Within 1-2hrs. endothelial cells express E-selectin.

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PAVEMENTING-HOW IT HAPPENS

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 Selectins bind to lectins on tips of leukocytes (with low affinity;

can be detached). This causes rolling.

 TNF & IL-1 induce endothelial expression of ICAM and VCAM

and bind to proteoglycans on endothelial cells and activate

leukocytes.

 Activated leukocytes go from low to high affinity state and bind

to ICAM-1 and VCAM-1 on endothelial surface.

 Leukocytes stop rolling and spread out over surface of

endothelial cell 19
 ENDOTHELIAL/ LEUKOCYTE ADHESION
MOLECULES
Endothelial Major Role
Molecule
P-selectin Rolling (neutrophils, monocytes,
lymphocytes
E-selectin Rolling, adhesion to activated
endothelium (monocytes,
lymphocytes, T cells)
ICAM-1 Adhesion, transmigration (all
leukocytes)
VCAM-1 Adhesion, transmigration Eosinophils,
monocytes, lymphocytes
GlyCam-1 Lymphocytes homing to endothelial
venules
PECAM (CD31) Leukocyte migration through
endothelium
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 EMIGRATIO
N
Process by which leukocytes escape from their location in the blood to reach
perivascular tissues (during mid inflammation)

 After adhesion- leukocytes move along the endothelial surface

 Insert large cytoplasmic extension pseudopodia into endothelial gaps

 Gaps created by actions of histamine and other chemical mediators and by

leukocytes themselves

 PECAM (Platelet Endothelial Cell Adhesion molecule) is important in this process

 Entire cell passes through once pseudopodia are through

 Collagenase breakdown basement membrane

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 Emigration occurs because there are adequate number of

inter-endothelial gaps and adequate number of receptors

(histamine)

 Emigration occurs during mid-inflammation

 Adhesion molecules (e.g. ICAM, VCAM), present on leukocyte

and endothelial cell surfaces, assist emigration

 The surface expression of these molecules can be induced, enhanced

or altered by inflammatory agents and chemical mediators

 Emigration is also regulated by chemotaxis ( unidirectional migration of

of cells along the chemical gradient) 22