Healing, repair & regeneration

• Healing: Replacement of dead cells &

damaged ECM (ExtraCellular Matrix) by
healthy tissue.
• It include two processes
– Regeneration of specialized cells (same cells).
– Repair: Replacement by connective tissue
characterized by the formation of granulation
tissue and its subsequent maturation.
The outcome of the healing is affected by:
1-the nature of the injury.
2-the severity of the injury.
3-the duration of the injury.
Extra-cellular Matrix (ECM)

• A major component of all tissue, provides

the backbone & support of the tissue.
• It consist of
– Fibrous structure portions
• Collagen
• Elastin
– Interstitial matrix
• Fibronectin
• Integrins
• Glycosaminoglycans
Repair by Regeneration

• Replacement injured tissue by same type

of original tissue cells.

• Labile & stable cells.

• It involves two tissue components:

– Cellular proliferation.
– ECM deposition.
Repair by connective tissue

• Three components

– Neovascularization (Angiogenesis)(granulation
tissue) formation.

– Migration & proliferation of fibroblast (fibrosis).

– Remodeling (fibrous tissue maturation &

organization).
• Granulation tissue:
– Proliferation of small new blood vessels &
fibroblasts in a loose ECM forming a specialized
type of tissue, it is the hallmark of healing.
– Growth factors: FGF & VEGF.
• Fibrosis:
– Fibroblast migration & proliferation.
– ECM deposition.
– Growth factors: PDGF, FGF, TGF-Beta, IL-1 & TNF.
• Remodeling:
– Fibrous tissue maturation & organization.
Healing of skin wounds

• 1. Healing by primary union

(Primary intention): Clean wound, its
edges are approximated e.g. surgical wounds.

• 2. Healing by secondary union

(Secondary union): Infected, contaminated
wound, large blood clot, edges are widely
separated.
 Cutaneous wound healing

It is generally divided into three overlapping

phases
• 1- Inflammation.
• 2- Granulation tissue formation and re-
epithelialization.
• 3- Wound contraction, extracellular matrix
deposition and remodeling.
Steps of wound healing
• Blood clots on wound surface & fills gap between
edges to seal the wound & bind the surfaces together.
• Acute inflammatory reaction with neutrophils then
macrophages that invade the blood clot & gradually
digest it as well as secreting GF.
• Basal epidermal cell proliferation & migration over
the wound surface to replace the surface defect.
• New blood vessels & granulation tissue formation
extends from wound edges & gradually replace the
blood clot.
• Fibroblast begin synthesizing ECM proteins esp.
collagen that bridges the wound.
• Continuous cross-linking & remodeling of
collagen occurs to increase the tensile strength of the
wound.
The phases of cutaneous wound healing
Injury leads to accumulation of platelets and
coagulation factors.
Coagulation results in fibrin formation and
release of PDGF and TGF-b and other
inflammatory mediators by activated platelets. This
leads to more Neutrophil recruitment which
signals the beginning of inflammation (24 h).
After 48 h macrophages replace neutrophils.
Neutrophils and macrophages are responsible for
removal of cellular debris and release growth
factors to reorganize the cellular matrix.
At 72 hours the proliferation phase begins as
recruited fibroblasts stimulated by FGF and
TFG-b begin to synthesize collagen. Previously
formed fibrin forms initial matrix for fibroblasts
Collagen cross-linking and reorganization
occurs following months after injury in the
remodeling phase of repair.
Wound contraction follows in large surface
wounds and is facilitated by actin-containing
fibroblasts (myofibroblasts)
 Factors Known to impair
healing
Local Factors Systemic Factors

• Infections • Nutritional
• Poor blood supply – protein lack
• Presence of foreign body – vitamin C deficiency
• Ionizing radiation – Zinc deficiency

• Continuous tissue • Systemic diseases

damage – D.M.
– Renal failure
• Mechanical factors
– systemic infections
– Excessive movement
– Hematoma • Corticosteroid treatment
Complications of wound healing
1.Infections.
2.Implantation dermoid cyst.
3.Painful scar.
4.Pigmented scar.
5.Cicatrisation.
6.Neoplastic changes.
7- Deficient scar formation
– Wound dehiscence
– Ulceration
8- Excessive formation of scar tissue
– Keloid (excessive collagen deposition)
– Exuberant granulation (proliferation of
fibroblasts that inhibits re-epithelialization)
– Desmoid (aggressive fibromatosis, semi-
malignant).
9- Contraction
Wound dehiscence Wound ulceration

Keloid Contracture
Wound contraction:
• Reduction of wound surface by 1/3 to 1/4 of its original
size by contraction of myofibrils of myofibroblasts.
Repair of other injured tissues:
• Cartilage--------------> Fibrosis.
• Tendon----------------> Fibrosis.
• Cardiac muscle----- -> Fibrosis.
• Skeletal muscle:
– If endomyseal tube preserved-------> regeneration.
– If endomyseal tube damaged--------> organization.
• Peripheral nerves:
• Endoneural tube preserved ---------> axon can
regenerate
• Liver cells-----------> Regenerate
• Renal tubules -------> Regenerate if the basement
membrane preserved.
• Glomeruli-----------> Fibrosis
Thank you