TISSUE REPAIR & HEALING

• REGENERATION (REPLACEMENT BY N-CELLS)

• REPAIR (REPLACEMENT BY CONNECTIVE TISSUE)
REPAIR BEGINS DURING INFLAMMATION

NEW VESSEL FORMATION (ANGIOGENESIS)

• PROTEOLYTIC ENZYME DIGESTS BASEMENT MEMBRANE
• MIGRATION OF ENDOTHELIAL CELLS
• PROLIFERATION OF ENDOTHELIAL CELLS
• MATURATION OF ENDOTHELIAL CELLS
• RECRUITMENT OF PERIENDOTHELIAL CELLS (PERICYTES & SMOOTH
MUSCLE CELLS)
CONTROLLED BY:
• PROMOTERS (GROWTH FACTORS)
• VASCULAR CELLS & EXTRACELLULAR MATRIX
• CYCLINS
TYPES OF CELLS vis-à-vis THE CELL CYCLE
1. LABILE CELLS: CONTINUOUSLY IN THE CYCLE eg EPITHELIAL CELLS,
SKIN, GIT, CERVIX
2. STABLE CELLS: IN Go PHASE, BUT CAN ENTER CYCLE AS REQUIRED eg.
PARENCHYMAL CELLS, HEPATOCYTES, ENDOTHELIUM
3. PERMANENT CELLS: CELLS THAT HAVE LEFT THE CYCLE eg NEURONS,
CARDIAC MUSCLE
MOLECULAR EVENTS IN CELL GROWTH
AUTOCRINE: SIGNAL FROM SAME CELL
PARACRINE: SIGNAL FROM CELL NEARBY
ENDOCRINE: SIGNAL FROM BLOOD STREAM
CELL SURFACE RECEPTORS
- FIBROBLAST GROWTH FACTOR (FGF)
- EPIDERMAL GROWTH FACTOR (EGF)
- PLATELET DERIVED GROWTH FACTOR (PDGF)
- VASCULAR ENDITHELIAL GROWTH FACTOR (VEGF)
RECEPTORS WITHOUT INTRINSIC CATALYTIC ACTIVITY
- CYTOKINES
G PROTEIN-LINKED RECEPTORS
CHEMOKINES
HEALING
FOLLOWS INFLAMMATION
ACUTE INFLAMMATION  CHRONIC INFLAMMATION
(DESTRUCTION OF PARENCHYMAL CELLS AND STROMAL FRAMEWORK)
HEALING BY FIRST OR SECOND INTENTION

1. REGENERATION OF PARENCHYMAL CELLS

2. MIGRATION & PROLIFERATION OF PARENCHYMAL & CONNECTIVE
TISSUE CELLS
3. SYNTHESIS OF ECM
4. REMODELLING OF CONNECTIVE TISSUE & PARENCHYMAL COMPONENTS
5. COLLAGENISATION & ACQUISITION OF WOUND STRENGTH (FIBROSIS /
SCARRING)
MIGRATION OF FIBROBLASTS TO THE SITE OF INJURY AND THEN
PROLIFERATION AT THAT SITE.
TRIGGERED BY PDGF, EGF, FGF,
TGFB, CYTOKINES

DEPOSITION OF EXTRACELULAR MATRIX

FIBROBLASTS LAY DOWN COLLAGEN
TYPES I, II, III = FIBRILLAR COLLAGEN
TYPES IV, V, VI + AMORPHOUS (IV + BASEMENT MEMBRANE)
COLLAGEN TENSILE STRENGTH TYPES I  IV
FIBRILS PLEATED & CROSS LINKED TO INCREASE TENSILE STRENGTH
PROLINE  HYDROXYPROLINE  CROSS LINKAGES (PRO-COLLAGEN -
COLLAGEN)
STIMULATED BY PDGF, FGF, TGF-B AND CYTOKINES SECRETED BY WBC
AND FIBROBLASTS
MATURATION & ORGANISATION (REMODELLING)
USE THE BM AS A “TEMPLATE”, NEED TO BREAK DOWN ECM IN ORDER TO
DEBRIDE WOUND
CONNECTIVE TISSUE REMODELLING
METALLOPROTEINASES:
GELATINASES (TYPE IV)
STROMELYSINS
COLLAGENASES (TYPES I, II & III)
ECM DEGRADATION INHIBITED BY TISSUE INHIBITORS OF
METALLOPROTEINASES
SECRETION OF ABOVE ENZYMES INHIBITED BY TGFβ & STEROIDS
FIBROBLASTS SYNTHESISE ELASTIC FIBRES AND SECRETE ECM
ECM COMPRISES
• COLLAGENS & ELASTINS
• ADHESIVE GLYCOPROTEINS (LAMININ) & INTEGRINS
• PROTEOGLYCANS & HYALURONAN
 FACTORS INVOLVED
INFLAMMATORY RESPONSE
GRANULATION TISSUES
PROTEIN
VITAMIN C
ZINC
GROWTH FACTORS
FACTORS AFFECTING WOUND HEALING
SYSTEMIC FACTORS:
• NUTRITION- ZN, PROTEIN & VIT C DEFICIENCIES
• METABOLIC STATUS – DIABETES MELLITUS
• CIRCULATORY STATUS – ARTERIOSCLEROSIS
• HORMONES - GLUCOCORTICOIDS
LOCAL FACTORS
• INFECTION
• MECHANICAL FACTORS – MOBILITY
• FOREIGN BODIES – UNNECESSARY SUTURES, FRAGMENTS OF GLASS,
STELL, SHRAPNEL OR BONE
• SIZE, LOCATION & TYPE OF WOUND
PATHOLOGICAL CONDITIONS
• KELOID
- EXCESS COLLAGEN
- GENETIC
- REPEATED TRAUMA
• PYOGENIC GRANULOMA “PROUD FLESH”
SUMMARY
- EXCESS GRANULATION TISSUE
- FEMALE
- SITES
REPAIR BEGINS EARLY ON IN INFLAMMATION (24 HRS).
BEGINS WITH THE FORMATION OF GRANULATION TISSUE (NEW
VESSELS AND FIBROBLASTS)
*GRANULATION TISSUE IS THE HALLMARK OF HEALING*