 Injury to cells and tissues sets in motion a

series of events that contain the damage

and initiate the healing process.
 Regeneration refers to the proliferation of
cells and tissues to replace lost structures
 Repair most often consists of a
combination of regeneration and scar
formation by the deposition of collagen
 Labile cells/ In continuously dividing
tissues cells
 Stabile Cells/ Quiescent tissues
 Permanent Cells/ Nondividing tissues
 Proliferate throughout life, replacing those that are
destroyed.
 surface epithelia (stratified squamous epithelia of the
skin, oral cavity, vagina, and cervix;
 the lining mucosa of all the excretory ducts of the
glands of the body (e.g., salivary glands, pancreas,
biliary tract);
 the columnar epithelium of the GI tract and uterus;
the transitional epithelium of the urinary tract,
 cells of the bone marrow and hematopoietic tissues.
 In most of these tissues mature cells are derived from
adult stem cells, which have a tremendous capacity
to proliferate and whose progeny may differentiate
into several kinds of cells
 Normally have a low level of replication;
 Cells from these tissues can undergo rapid division in
response to stimuli and are thus capable of
reconstituting the tissue of origin.
 Parenchymal cells of liver, kidneys, and pancreas;
mesenchymal cells such as fibroblasts and smooth
muscle; vascular endothelial cells; and lymphocytes
and other leukocytes.
 Fibroblasts, endothelial cells, smooth muscle cells,
chondrocytes, and osteocytes are quiescent in adult
mammals but proliferate in response to injury.
 Fibroblasts in particular can proliferate extensively, as
in healing processes and fibrosis,
 Contain cells that have left the cell cycle and cannot
undergo mitotic division in postnatal life.
 Neurons and skeletal and cardiac muscle cells.
 If neurons in the CNS are destroyed CNS–supportive
elements(glial cells). Limited neurogenesis from stem
cells may occur
 Skeletal muscle does have regenerative capacity,
through the differentiation of the satellite cells that are
attached to the endomysial sheaths.
 Cardiac muscle has very limited, if any, regenerative
capacity, and a large injury to the heart muscle, as
may occur in myocardial infarction, is followed by
scar formation.
 Self-renewal properties
and by their capacity
to generate
differentiated cell lineages
(a) obligatory asymmetric replication and
(b) stochastic differentiation
Differentiated cells of adult
tissues can be
reprogrammed to become
pluripotent by transferring
their nucleus to an
enucleated oocyte.
EGF
 Epidermal growth
 Platelets, macrophages, saliva, urine, milk,
plasma
 Mitogenic for keratinocytes and fibroblasts;
stimulates keratinocyte migration and
granulation tissue formation
TGF-α
 Transforming growth factor α
 Macrophages, T lymphocytes, keratinocytes,
and many tissues Similar to EGF
 Stimulates replication of hepatocytes and most
epithelial cells
HB-EGF
 Heparin-binding EGF
 Macrophages
 Mesenchymal cells Keratinocyte replication

HGF
 Hepatocyte growth factor/scatter factor
 Mesenchymal cells
 Enhances proliferation of hepatocytes,
epithelial cells, and endothelial cells;
 Increases cell motility, keratinocyte
replication
VEGF
 Vascular endothelial cell growth factor
(isoforms A, B, C, D)
 Many types of cells Increases vascular
permeability
 Mitogenic for endothelial cells
 Angiogenesis
PDGF
 Platelet-derived growth factor (isoforms A, B, C, D)
 Platelets, macrophages, endothelial cells,
keratinocytes, smooth muscle cells
 Chemotactic for PMNs, macrophages, fibroblasts,
and smooth muscle cells;
 Mitogenic for fibroblasts, endothelial cells, and
smooth muscle cells;
 Stimulates prod of matrix metalloproteinases
(MMPs), fibronectin, and HA;
 Stimulates angiogenesis and wound contraction
FGF
 Fibroblast growth factor 1 (acidic), 2
(basic), and family
 Macrophages, mast cells, T lymphocytes,
endothelial cells, fibroblasts
 Chemotactic for fibroblasts
 Mitogenic for fibroblasts and keratinocytes;
 Stimulates keratinocyte migration,
 Angiogenesis, Wound contraction
 Matrix deposition
TGF-β
 Transforming growth factor β (isoforms 1, 2, 3); BMPs
and activin
 Platelets, T lymphocytes, macrophages,
endothelial cells, keratinocytes, smooth muscle
cells, fibroblasts
 Chemotactic for PMNs, macrophages,
lymphocytes, fibroblasts, and smooth muscle cells
 Stimulates TIMP synthesis,
 Angiogenesis, and fibroplasia
 Inhibits production of MMPs
 Keratinocyte proliferation
KGF
 Keratinocyte growth factor (FGF-7)
 Fibroblasts
 Stimulates keratinocyte migration,
proliferation, and differentiation

TNF
 Tumor necrosis factor
 Macrophages, mast cells, T lymphocytes
 Activates macrophages
 Regulates other cytokines; multiple functions
 Autokrin : respon imun,
hiperplasia epitel
kompensatoris
 Parakrin: difusi min sel
berdekatan
 Endokrin: sel target
jauh
 Sinaptik
 Mechanical support for cell anchorage and
cell migration, and maintenance of cell
polarity
 Control of cell growth
 Maintenance of cell differentiation
 Scaffolding for tissue renewal
 Establishment of tissue microenvironments.
 Storage and presentation of regulatory
molecules.
 Degradasi diatur oleh MMPs
Macromolecules:
1. Fibrous Structural Proteins: collagens
and elastins that provide tensile strength
and recoil;
2. Adhesive Glycoproteins that connect
the matrix elements to one another and
to cells
3. Proteoglycans and Hyaluronan that
provide resilience and lubrication.
2 Basic forms:
 Interstitial Matrix
 Found in spaces between epithelial,
endothelial, and smooth muscle cells, as well
as in connective tissue.
 It consists mostly of fibrillar and nonfibrillar
collagen, elastin, fibronectin, proteoglycans,
and hyaluronan.
 Basement Membranes
 Associated with cell surfaces
 Consist of nonfibrillar collagen (mostly type
IV), laminin, heparin sulfate, and
proteoglycans.
 Inflammation
 Angiogenesis
 Migration and proliferation of fibroblasts
 Scar formation
 connective tissue remodeling.
 Embrio: vaskulogenesis dr angioblas/ hemangioblas.
Dewasa: neovaskularisasi
 Vasodilation in response to NO and VEGF
 Proteolytic degradation of the BM of the parent vessel
by MMPs and disruption of cell-to-cell contact between
endothelial cells by plasminogen activator
 Migration of endothelial cells toward the angiogenic
stimulus
 Proliferation of endothelial cells, just behind the leading
front of migrating cells
 Maturation of endothelial cells, which includes
inhibition of growth and remodeling into capillary tubes
 Recruitment of periendothelial cells (pericytes and
vascular smooth muscle cells) to form the mature
vessel
 Formation of blood clot
 Formation of granulation tissue
 Proliferasi sel dan deposisi kolagen
 Scar formation
 Wound contraction
 Connective tissue remodelling
 Recovery of tensile strength
Systemic factors :
 Nutrition.
 Metabolic status .
 Circulatory status.
 Hormones

Local factors
 Infection >>>
 Mechanical factors
 Foreign bodies
 Size, location (vaskularisasi), and type of
wound.
 Inadequate formation of granulation
tissue or assembly of a scar can lead to
two types of complications: wound
dehiscence and ulceration
Excessive formation of the
components of the repair
process: hypertrophic scars
and keloids
Contraction in the size of a wound exaggeration:
contracture and results in deformities of the wound and
the surrounding tissues