TISSUE REPAIR

Regeneration, Healing and Fibrosis

Ris Kristiana, dr., SpPA

Objectives Upon completion of this lecture,
the student should:
• Describe the differences between repair processes: regeneration, healing and
fibrosis. List examples of each cell type.
• Know the differences between the various cell in regenerative abilities types.
• Know the mechanism of repair and formation of granulation tissue.
• List the three main phases of cutaneous wound healing.
• Compare and contrast the difference between healing by primary intention
and healing by secondary intention.
• List factors which are associated with delayed wound healing.
• List complication of wound healing
Repair : restoration of tissue architecture and
fuction after an injury

→Regeneration → return to normal state

→Healing → result scar formation
IF fibrosis develops in a tissue space occupied by
inflammatory exudate → organization
→Involves the proliferation of various cell
→Interactions between cells and the ECM (extracellular
matrix)
Tissue types according to ability of Cell
Proliferations
Cell Proliferations
• Physiologic proliferations → repair
• Pathologic proliferations → cancer
• Proliferations vs apoptosis → balance populations
of cell
• The key processes are DNA replications and
mitosis → Cell cycle
• Triggered by : growth factors, hormones, cytokines, ECM
signals
 Growth factor
mechanism :
- Stimulating cellular
proliferations
- Stimulate migration,
differentiation,
synthesis protein,
stimulation
angiogenesis,
fibrogenesis
ECM and cell matrix interactions
• ECM is a dynamic, constantly remodeling macromolecular complex
synthezied locally, which assembles into a network that sorrounds
cells.
• Regulate the proliferation, movement and differentiation of cells
• Occure in 2 basics form : interstitial matrix and basement membrane
Interstitial matrix
• Present in the space between cells in connective tissue
• Between epithelium
• Suported vascular and smooth muscle structure
• Synthesized by mesenchymal cells (e.g fibroblasts)
• Amorphous gel, major constituents : fibrillar and nonfibrillar collagen
(fibronectin, elastin, proteoglycans, hyaluronate)
Basment membrane
• Interstitial matrix in connective tissue arounds epithelial cell,
endothelial, smooth muscle
• Lies beneath epithelium; synthesized by overlying epithelium and
underlying mesenchymal cells
• Major constituents : amorphous non fibrillar type IV collagen and
laminin
Role of ECM
• Mechanical support for cell anchorage and cell migration, and
maintain of cell polarity
• Control of cell growth
• Maintenance of cell differentiation
• Scafolding the tissue renewal
• Establishment of tissue microenvironment
• Storage and presentation of regulatory molecules
Component of ECM

- Collagen and elastin → strength and

recoil
- Proteoglycan and hyaluronan →
water hydrat gel permit resilience and
lubricant
- Adhesive glycoprotein and adhesion
receptors → connect matrix element to
one another and to cells
Cells and Tissue Regeneration
• Cell renewal continuously in labile cell (bone marrow, epithel, skin)
• Damage epithel can be corrected by : proliferation & differentiation
stem cell in the bone marrow
• Tissue regeneration can occur in stable cell population too (pancreas,
liver, adrenal, thyroid)
• Regeneration can occur only if the residual tissue is intact (structure
and function)
• If the tissue damage by infection or inflammation →regeneration
incomplete →scarring
Repair By Connective Tissue
• If :
→tissue injury severe or chronic
→damage parenchymal cell and epithelial
→The injury cell are nondividing cell
Repair can not be
accomplished by regeneration
alone

Repair occur by replacement the non

regenerated cell with connective tissue /
combination of regeneration some cell and
scar formation
Repair By Connective Tissue (HEALING)
• Maturation and
reorganizatiuons of
• Emigration of fibroblast fibrous tissue
• Induction of fibroblast (REMODELING)
In 24 hours • Endothelial proliferation

3-5 days

Granulation tissue :
- Fibroblast proliferations SCAR
HEALING Deposition ECM
- Angiogenesis
- Macrophage and
inflammatory cells
Repair By Connective Tissue (HEALING/
Granulation Tissue)
Consist of 4 sequential processes :
• Angiogenesis
• Migration and proliferation of fibroblast
• Scar formation
• Remodeling (maturation and reorganization of fibrous tissue)
 Angiogenesis
- Vasoditalation, increase
permeability induce by VEGF
- Endothelial migration to the
injury area
- Endothelial proliferations
- Inhibition of endothelial cell
proliferation and remodeling into
capillary tube
- Recruitment of periendothelial
cells (pericytes for small vessel.
Smc for larger vessel) to form the
mature vessel
Fibroblast Migration and ECM deposition
(Scar formation)
The main two steps :
1. Migration and proliferation of fibroblast into the site of injury
2. Deposition of ECM
3. Driven by : PDGF, FGF-2, TGF-ß
ECM and Tissue Remodeling
CUTANEUS WOUND HEALING
1. Inflamation
2. Formation granulation
tissue
3. ECM deposition and
remodeling
Delay Wound Healing, the most caused by :
Complications in cutaneus wound healing
Alhamdulillah…
Thank you for attention