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Granulation Tissue
Injury
Bloodmaterial interactions
Provisional matrix formation
Acute inflammation
Granulation tissue
Foreign body reaction
Fibrosis/fibrous capsule development
1. Superficial wound
2. Partial thickness wound
3. Full thickness wound
4. Wound related with muscles, tendon and
bone.
Based on the healing time :
1. Acute wound ( > 12 weeks)
2. Chronic wound ( < 12 weeks) unhealed
wound because endogen factor and exogen factor.
1.
3.
2.
4.
DEFINITIONS:
Repair
Phases of healing
1.
2.
3.
4.
Hemostasis
Inflammation ( 0-3 days after injury)
Proliferation ( 3-21 days )
Maturation ( 21 days 1,5 years)
Extracellular matrix
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Hemostasis
4 major events :
1. The initial phase of the process is vascular constriction. This
limits the flow of blood to the area of injury.
2. Next, platelets become activated by thrombin and aggregate at
the site of injury, forming a temporary, loose platelet plug.
3. To insure stability of the initially loose platelet plug, a fibrin mesh
(also called the clot) forms and entraps the plug.
4. Finally, the clot must be dissolved in order for normal blood flow
to resume following tissue repair. The dissolution of the clot occurs
through the action of plasmin (important enzyme present in blood
that degrades many blood plasma proteins, including fibrin clots.
The degradation of fibrin is termed fibrinolysis.)
Inflammation
0- 3 days after injury
5 cardinal of inflammation :
a. rubor /redness
b.tumor / swelling
b. calor/ heat
c. dolor / pain
e. functiolaesa
Inflammation signs
Rubor arteriol are supplied blood, dilatation,
more blood sirculate to local microsirculation.
Empty capillarie then would be full of blood
(hyperemia / congestion) cause localized red/
acute inflammation
Calor inflammation area could be hotter
compared with the surrounding area because
blood number which sirculate in that area are
more than normal area.
Inflammation signs
Proliferation
Proliferation : period during which new cells
fill and seal a wound
occurs from 2 days to 3 weeks after the
inflammatory phase.
Characterized
by
the
appearance
of
granulation tissue (combination of new blood
vessels, fibroblasts, and epithelial cells ), bright
pink to red because of the extensive projections
of capillaries in the area.
What is granulation ?
The term granulation tissue was used by ancient surgeons for
the red, granular tissue filling the non healing wounds.
Granulation tissue occurs in all wounds during healing and
may occur in chronic inflammation as well
It consists of fibroblasts surrounded by abundant extracellular
matrix (the extracellular part of multicellular structure (e.g.,
organisms, tissues, biofilms) that typically provides structural and
biochemical support to the surrounding cells), newly formed blood
vessels, and scattered macrophages (its function in both nonspecific defense (innate immunity) as well as help initiate specific
defense mechanisms (adaptive immunity) and some other
inflammatory cells (neutrophil, macrophage, monocyte, eosinophil,
basophil).
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GRANULATION
Granulation tissue grows from the
wound margin toward the center.
It is fragile and easily disrupted by
physical or chemical means.
As more and more fibroblasts
produce collagen (a tough and
inelastic protein substance), the
adhesive strength of the wound
increases.
light red or dark pink in color, being
perfused (permeated) with new
capillary loops or "buds"; soft to the
touch; moist; and bumpy (granular)
in appearance
Granulation tissue is composed of tissue matrix supporting a variety of cell types, most
of which can be associated with one of the following functions:
1. extracellular matrix (cell adhesion, cell-to-cell communication and differentiation are
common functions of the ECM)
The extracellular matrix of granulation tissue is created and modified by fibroblasts.
Initially, it consists of a network of type-III collagen, a weaker form of the structural
protein that can be produced rapidly. This is later replaced by the stronger, longstranded type-I collagen, as evidenced in scar tissue.
2. immune system (The main immune cells active in the tissue are macrophages and
neutrophils, although other leukocytes are also present. These work to phagocytize old
or damaged tissue, and protect the healing tissue from pathogenic infection. This is
necessary both to aid the healing process and to protect against invading pathogens, as
the wound often does not have an effective skin barrier to act as a first line of defense).
3. Vascularisation (It is necessary for a network of blood vessels to be established as soon as
possible to provide the growing tissue with nutrients, to take away cellular wastes, and
transport new leukocytes to the area. Fibroblasts, the main cells that deposit granulation
tissue, depend on oxygen to proliferate and lay down the new extracellular matrix).
GRANULATION TISSUE
The healing response ( 1 day after implantation) is initiated by :
1. action of monocytes and macrophages
(1) replenishing resident macrophages and dendritic cells under normal states,
and
(2) in response to inflammation signals, monocytes can move quickly (approx.
812 hours) to sites of infection in the tissues and divide/differentiate into
macrophages and dendritic cells to elicit an immune response.
Dendritic cells (DCs) are antigen-presenting cells, (also known as accessory
cells) of the mammalian immune system. Their main function is to process
antigen material and present it on the cell surface to the T cells of the immune
system. They act as messengers between the innate and the
adaptive immune systems.
Dendritic cells are present in those tissues that are in contact with the external
environment, such as the skin (where there is a specialized dendritic cell type
called the Langerhans cell) and the inner lining of the nose, lungs, stomach and
intestines.
2. proliferation of fibroblasts and vascular endothelial cells at the
implant site,
3. leading to the formation of granulation tissue
4. the standard of healing inflammation.
Dendritic cells
Summary
Proteoglycans
Proteoglycans are a major component of the
extracellular matrix, the "filler" substance
existing between cells in an organism.
Function :
involved in binding cations (such as sodium,
potassium and calcium) and water,
also regulating the movement of molecules
through the matrix.
affect the activity and stability of proteins and
signalling molecules within the matrix.
Fibronectin
Fibronectin is a high-molecular weight
(~440kDa) glycoprotein of the
extracellular matrix that binds to membranespanning receptor proteins called integrins).
Functions :
Plays a major role in cell adhesion, growth,
migration, and differentiation, and it is
important for processes such as wound healing
and embryonic development.