3. • Tissue repair: restoration of tissue architecture and function after
an injury
• Occurs in two ways:
• Regeneration of injured tissue.
• Replacement by connective tissue (scarring)
4. • Usually, tissue repair involves both processes
• Involves cell proliferation, and interaction between cells and
extracellular matrix.
5. • Many cells proliferate during tissue repair:
• Injured tissue remnants.
• Vascular endothelial cells
• Fibroblasts
6. Tissues of the body are divided into three groups:
•Continuously dividing (labile) tissues.
•Stable tissues.
•Permanent tissues
7. •Continuously dividing (labile) tissues
•Cells are continuously proliferating.
•Can easily regenerate after injury
•Contain a pool of stem cells
•Examples: bone marrow, skin, GIT epithelium.
10. •Stable tissues
•Cells have limited ability to proliferate.
•Limited ability to regenerate (except liver!)
•Normally in G0, but can proliferate if injured.
•Examples: liver, kidney, pancreas…
12. GROWTH FACTORS
•Very important in tissue repair.
•Actions:
•Stimulate cell division and proliferation.
•Promote cell survival.
13. THE EXTRACELLULAR MATRIX
•ECM is the network that surrounds cells. It is two forms: interstitial
matrix and basement membrane.
•ECM regulates proliferation, movement, and differentiation of the
cells living in it.
14. REGENERATION
•Occurs all the time in labile tissues
•Cells are constantly being lost and replaced
•If demand increases, supply increases easily
15. •Occurs in limited form in stable tissues
•Remove one kidney: the other one undergoes hypertrophy and
hyperplasia
•Remove half of the liver: it will grow back
16. SCARRING
•If injury is severe, regeneration can’t happen
•So, fibrosis (a scar) replaces the injured tissue
17. •Four components to this process:
•New vessel formation (Angiogenesis).
•Fibroblast proliferation.
•Synthesis of collagen (Scar formation).
•Remodeling of the scar.
18. •By 24 hours:
•Endothelial cells start proliferating
•Fibroblasts emigrate
•By 3-5 days:
•Granulation tissue present (blood vessels+ fibroblasts).
•Weeks later:
•Dense fibrosis (scar)
•Scar is remodeled over time
19.
20.
21. Introduction to wound healing
• Healing is a complex and dynamic process of restoring cellular structures
and tissue layers.
• The adult wound healing process can be divided into 4 distinct phases:
• The homeostasis phase
• the inflammatory phase
• the proliferative phase
• the remodeling phase.
22. Sequence of events in healing
Initial phase - Hemostasis
• Following vasoconstriction, platelets adhere to damaged
endothelium and discharge adenosine diphosphate (ADP),
promoting thrombocyte clumping, which dams the Wound
23. • The inflammatory phase is initiated by the release of numerous
cytokines by platelets.
• Fibrinogen is cleaved into fibrin and the framework for
completion of the coagulation process is formed.
24. Second phase - Inflammation
• Within the first 6-8 hours
• polymorph nuclear leukocytes (PMNs) “cleanse” the wound, clearing it of
debris , monocytes also exude from the vessels. These are termed
macrophages. The macrophages continue the cleansing process and
manufacture various growth factors during days 3-4.
25. Third phase - Granulation
sub phases are: fibroplasia -matrix deposition - angiogenesis -
and re-epithelialization
• In days 5-7, fibroblasts have migrated into the wound, laying
down new collagen of the subtypes I and III
26. • Angiogenesis . The formation of new vasculature requires
migration, mitosis, and maturation of endothelial cells
• Re-epithelization occurs with the migration of cells from the
periphery of the wound . Division of peripheral cells occurs in
hours 48-72, resulting in a thin epithelial cell layer, which bridges
the wound.
27. Fourth phase - Remodeling After the third week, the wound
undergoes constant alterations, known as remodeling,
• This can last for years after the initial injury occurred. Collagen
is degraded and deposited in an equilibrium-producing fashion
28. • Contraction of the wound is an ongoing process resulting in part
from the proliferation of the specialized fibroblasts termed
myofibroblasts, which resemble contractile smooth muscle cells.
29. 1. SKIN WOUND HEALING
• First intention
• Second intention
30.
31. Healing by First Intention
•Occurs in small wounds that close easily
•Epithelial regeneration predominates over fibrosis
•Healing is fast, with minimal scarring/infection
•Example: Well-approximated surgical incisions
32. Healing by First Intention: Timeline
• By 24 hours
• Clot forms
• Neutrophils come in
• Epithelium begins to regenerate
33. • By 3-7 days
• Macrophages come in
• Granulation tissue is formed
New blood vessels
Fibroblasts
• Collagen begins to bridge incision
• Epithelium increases in thickness
34. • Weeks later
• Granulation tissue gone
• Collagen is remodeled
• Epidermis is full and mature, but without dermal
appendages.
35.
36.
37.
38. Healing by Second Intention
• Occurs in larger wounds that have gaps between wound margins
• Fibrosis predominates over epithelial regeneration
• Healing is slower, with more inflammation and granulation tissue
formation, and more scarring
43. FACTORS AFFECTING WOUND HEALING
Local factors
• Infection is the single most important cause of delay in healing.
• Mechanical factors, as early motion of wounds, can delay healing.
• Foreign bodies, such as fragments of steel, glass, or even bone
44. • Size, location, and type of wound influence healing. Wounds in
richly vascularized areas, such as the face, heal faster than those in
poorly vascularized
45. General Factors
• Age
• General state of health
• chronic diseases e.g. diabetes, rheumatoid arthritis etc.
• Drugs (steroids) and hormones
• General cardiovascular status
46. • General dietary deficiencies e.g. protein
• Specific dietary deficiencies
• Vitamin C
• sulphur-containing amino acids
