1. The document discusses the process of wound healing, which involves regeneration and repair through distinct phases - inflammatory, proliferative, and maturation. 2. During the inflammatory phase, platelets form clots to stop bleeding while macrophages and leukocytes remove debris. Growth factors are released to stimulate healing. 3. In the proliferative phase, new tissue is formed through granulation, angiogenesis, collagen deposition, epithelialization, and contraction. 4. Finally, in the maturation phase scar tissue is remodeled and strengthened over time through collagen remodeling.

1. REPAIR
PRESENTED BY:
PRABLEEN ARORA
MDS STUDENT

2. • Healing is the body’s response to injury in an
attempt to restore normal structure and function.
This involves 2 distinct process:
Refers to the
reproduction or
reconstitution of a lost
or injured tissues that
the architecture and
function of the lost or
injured tissues are
completely restored.
results in complete
restoration of original
tissues.
Refers to healing of a
wound in response to
injury in an attempt
to restore normal
structure and
function.
resulting in fibrosis
and scarring.
REGENERATION REPAIR

4. REPAIR
• It is the replacement of injured tissue by fibrous
tissue. Two processes are involved in repair:
• Granulation tissue formation
• Contraction of wounds.
• REPAIR response takes place by participation of :
1. mesenchymal cells ( consisting of connective tissue
stem cells, fibroblast and histiocytes)
2. endothelial cells,
3. macrophages, platelets,
4. the parenchymal cells of the injured organ.

5. WOUND HEALING

8. EPINEPHRINE
RELEASED
PLATELET
AGGREGATION
STIMULATED
α-GRANULES
RELEASED
Alpha granules contain a variety of
immunomodulatory and proteinaceous
factors. These factors include:
• Albumin, Fibrinogen, Fibronectin , IgG, and
Coagulation Factors V and VIII, as well as
• Platelet-Derived Growth Factor (PDGF),
•Transforming Growth Factors α and β (TGF-α
and TGF-β)
•Fibroblast Growth Factor-2 (FGF-2),
•Platelet-Derived Epidermal Growth Factors
(EGFs),
•Endothelial Cell Growth Factors.

9. The actions of the intrinsic and extrinsic pathways result in the production of
thrombin
catalyzes the conversion of
fibrinogen fibrin
(forms the meshwork that stabilizes the platelet plug )
Thrombin itself stimulates increased vascular permeability in addition to facilitating the
extravascular migration of inflammatory cells.

10. INFLAMMATORY PHASE
• Characterised by Leukocytes and
Macrophages.
• One of the primary functions of
inflammation is to bring
inflammatory cells to the injured
area mediated via various
chemokines.
• These cells then destroy
bacteria and eliminate debris
from dying cells and damaged
matrix so that the repair
processes can proceed.
redness
Swelling
heat
pain
loss of function

11. The directed movement of leukocytes
from blood into the local tissue by
transendothelial migration is central to
the inflammation.
•Leukocyte migration into the wounded
area is stimulated by:
•Collagen
• elastin breakdown products,
•complement factors
•immunomodulatory factors
 Transforming Growth Factor–β (TGFβ),
 Tumor Necrosis Factor-α (TNF-α),
Interleukin-1 (IL-1),
 Platelet Derived Growth Factors
(PDGF),
Leukotriene B4 & Platelet Factor IV.

12. •Leukocytes are activated by
chemostatic factors and initiate
cellular wound debridement by
phagocytosing bacteria and
foreign material .
•The added function of cytokine
production differentiates the
activities of the two cell types
and makes macrophages more
essential.
•About 4 days after injury macrophages work to destroy
bacteria, cleansing the wound of cellular debris.
•Macrophages replace leukocytes and produce host of
cytokines and growth factors.
•Macrophage-produced cytokines are involved in
>angiogenesis
>fibroblast migration and proliferation,
>collagen production
>possibly wound contraction

13. • Macrophage-produced cytokines:
• Transforming Growth Factor- β (TGF-β),
• Interleukin -1 (IL-1),
• Insulin-like Growth Factor-1 (IGF-1),
• Fibroblast Growth Factor -2 (FGF-2),
• Platelet Derived Growth Factor (PDGF)

14. PROLIFERATIVE PHASE
The proliferative phase begins with activation of
fibroblasts by the growth factors released by
macrophages that populate the initial fibrin–fibrinogen
matrix.
Once the fibroblasts migrate into the wound, they
become active and increase protein synthesis.
Become the prominent cell type by 3 to 5 days in clean,
noninfected wounds.
 After cell division and proliferation, fibroblasts begin
synthesis and secretion of extracellular matrix products.
The initial wound matrix is provisional.
Collagens types I (80% - 90%) and III (10% - 20%) are
deposited by fibroblasts.
Collagen synthesis is stimulated by TGF-β, PDGF & EGF.
Maximal rate for 2 to 4 weeks.
GRANULATION

15. Granulation
• New connective tissue begins to form approx 2–4
days after wounding, and it is called granulation
tissue.
• Consists of blood clot, fibroblasts and their
progenitor cells, new loose and primitive connective
tissue ECM produced by wound fibroblasts, new
and forming blood vessels and inflammatory cells

16. ANGIOGENISIS
• Active from 2nd day after wounding.
•Angiogenesis involves the branching and
extension of adjacent pre-existing vessels.
•During angiogenesis, endothelial sprouts
derive from intact capillaries at the wound
periphery .
• The sprouts grow through cellular
migration and proliferation.
•Eventually, the endothelial sprout comes
into contact with a sprout derived from a
different capillary, and they interconnect
generating a new capillary.
• Regulated mainly by FGF-2 and VEGF.

17. CONTRACTION
CONTRACTION
•Contraction that begin to predominate 4 to 5 days after
wounding.
• Wound contraction is characterized by a predominance of
myofibroblasts at the wound periphery.
•Myofibroblasts are modified fibroblasts .
•The differentiation of myofibroblasts occurs between 6 and
15 days after wounding.
•After 15 days, about 70% of fibroblasts in granulation tissue
express a-smooth muscle actin.
•The induction of a-smooth muscle actin expression during
wound repair is thought to provide a mechanism to stop
fibroblast migration when cells reach their destination.
•Termination of migration and formation of prominent focal
adhesions may be needed to promote stable cell adhesion to
matrix, which is required for myofibroblasts to acquire a
matrix-synthesizing and contractile phenotype.

18. • When contraction stops, the myofibroblasts disappear
because of apoptosis and the scar becomes less cellular
and new fibroblasts with properties typical to normal
connective tissue fibroblasts emerge.
• Apoptosis of myofibroblasts begins at day 12,
peaks at day 20
resolves by day 60 after wounding
• It has been noted that interferon-g has an antifibrotic
effect, which probably results fromits ability to inhibit
fibroblast differentiation into myofibroblasts.

19. EPITHELIALIZATION
EPITHELIALIZATION
•Reconstruction of injured epithelium begins almost
immediately after wounding.
•Approximately 24 hours after the initiation of cellular
migration, basal cells at the wound edge begin to proliferate,
contributing additional cells to the healing monolayer.
•The migration of epithelial cells continues until overlap is
achieved with other epithelial cells migrating from different
directions.
•At that point, “contact inhibition‘‘ results in cessation of
cellular migration.
•The processes of cellular migration and proliferation occur
under the control of various cytokines

20. • Epithelial cell migration requires the development of actin
filaments within the cytoplasm of migratory cells and the
disappearance of desmosomes and hemidesmosomes that
link them to one another and to the basement membrane,
respectively.
• If the epidermal basement membrane is intact, cells simply
migrate over it. In wounds in which it has been destroyed,
the cells initially begin to migrate over the fibrin–
fibronectin provisional matrix.
• When contact inhibition is achieved, hemidesmosomes re-
form between the cells and basement membrane, and
tenasin and vitronectin secretion diminishes

21. MATURATION
•REMODELLING
•Scar remodelling begins to predominate approximately 21 days after injury.
•The rate of collagen synthesis diminishes.
•The nature of the wound matrix changes with scar remodelling.
• Immature scar contains a disorganized array of fine collagen fibers, which is gradually replaced
by thicker fibers arranged in an orientation paralleling stresses.
COLLAGEN MATURATION

22. • The remodelling process is associated with a substantial
increase in wound-breaking strength.
• Wound strength 1 week after injury is 3% of normal dermis.
• After 3 weeks, when the remodelling phase begins to
predominate, the wound will have only approximately 20% the
strength of normal dermis.
• At 3 months, the wound will have 80% the strength of normal
dermis, with the significant increase in strength resulting from
the contribution of remodelling.
• Remodelling will continue for up to 12 months after a wound is
created, although scars never regain the strength of normal
dermis.

23. WOUND HEALING
Combination of regeneration and repair.
• Wound healing can be accomplished in one of
the following two ways:
• Healing by first intention (primary union)
• Healing by second intention (secondary union)

24. WOUND HEALING
Healing by First
Intention
• Clean and uninfected
• Surgically incised
• Without much loss of
cells and tissues
• Edges are
approximately sutured
by surgical sutures.
Healing by Second
Intention
•Open with large tissue
defect
•Having extensive loss of
cells and tissues
•The wound is not
approximated by surgical

25. The sequence of events in primary union.
1. Initial haemorrhage. Immediately after injury, the space between the approximated surfaces
of incised wound is filled with blood which then clots and seals the wound against
dehydration and infection.
2. Acute inflammatory response. This occurs within 24 hours with appearance of polymorphs
from the margins of incision. By 3rd day, polymorphs are replaced by macrophages.

26. 3. Epithelial changes. The basal cells of epidermis from both the cut
margins start proliferating and migrating towards incisional space in
the form of epithelial spurs.
• A well-approximated wound is covered by a layer of epithelium in 48
hours.
• The migrated epidermal cells separate the underlying viable dermis
from the overlying necrotic material and clot, forming scab which is
cast off.
• The basal cells from the margins continue to divide. By 5th day, a
multilayered new epidermis is formed which is differentiated into
superficial and deeper layers.
4. Organisation. By 3rd day, fibroblasts also invade the wound area. By
5th day, new collagen fibrils start forming which dominate till healing
is completed. In 4 weeks, the scar tissue with scanty cellular and
vascular elements, a few inflammatory cells and epithelialised surface
is formed.

27. 5. Suture tracks.
Each suture track is a separate wound and incites the
same phenomena as in healing of the primary wound
i.e. filling the space with haemorrhage, some
inflammatory cell reaction, epithelial cell proliferation
along the suture track from both margins, fibroblastic
proliferation and formation of young collagen.
• When sutures are removed around 7th day, much of
epithelialised suture track is avulsed and the remaining
epithelial tissue in the track is absorbed.
• However, sometimes the suture track gets infected
(stitch abscess), or the epithelial cells may persist in the
track (implantation or epidermal cysts).

28. • Thus, the scar formed in a sutured wound is
neat due to close apposition of the margins of
wound; the use of adhesive tapes avoids
removal of stitches and its complications

29. Healing by Second Intention
• This is defined as healing of a wound having the following
characteristics:
i) open with a large tissue defect, at times infected
ii) having extensive loss of cells and tissues
iii) the wound is not approximated by surgical sutures but is left
open.
• The basic events in secondary union are similar to primary
union but differ in having a larger tissue defect which has to
be bridged.
• Hence, healing takes place from the base upwards as well as
from the margins inwards.
• The healing by second intention is slow and results in a large,
at times ugly, scar as compared to rapid healing and neat scar
of primary union.

30. A, The open wound is filled with blood clot and there is inflammatory response at the junction
of viable tissue.
B, Epithelial spurs from the margins of wound meet in the middle to cover the gap and
separate the underlying viable tissue from necrotic tissue at the surface forming scab.
C, After contraction of the wound, a scar smaller than the original wound is left.

31. 1. Initial haemorrhage. As a result of injury, the wound space is
filled with blood and fibrin clot which dries.
2. Inflammatory phase. There is an initial acute inflammatory
response followed by appearance of macrophages which
clear off the debris as in primary union.
3. Epithelial changes. As in primary healing, the epidermal cells
from both the margins of wound proliferate and migrate into
the wound in the form of epithelial spurs till they meet in the
middle and re-epithelialise the gap completely.
However, the proliferating epithelial cells do not cover the
surface fully until granulation tissue from base has started
filling the wound space.
• In this way, preexisting viable connective tissue is separated
from necrotic material and clot on the surface, forming scab
which is cast off. In time, the regenerated epidermis becomes
stratified and keratinised.

32. • Granulation tissue. Main bulk of secondary healing is
by granulations. Granulation tissue is formed by
proliferation of fibroblasts and neovascularisation from
the adjoining viable elements.
• The newly-formed granulation tissue is deep red,
granular and very fragile. With time, the scar on
maturation becomes pale and white due to increase in
collagen and decrease in vascularity.
• 5. Wound contraction. Contraction of wound is an
important feature of secondary healing, not seen in
primary healing.
• Due to the action of myofibroblasts present in
granulation tissue, the wound contracts to one-third to
onefourth of its original size. Wound contraction occurs
at a time when active granulation tissue is being
formed.

33. • 6. Presence of infection. Bacterial contamination
of an open wound delays the process of healing due
to release of bacterial toxins that provoke necrosis,
suppuration and thrombosis. Surgical removal of
dead and necrosed tissue, debridement, helps in
preventing the bacterial infection of open wounds.

34. Complication of wound healing
• 1. Infection of wound due to entry of bacteria delays the
healing.
• 2. Implantation (epidermal) cyst formation may occur
due to persistence of epithelial cells in the wound after
healing.
• 3. Pigmentation. Healed wounds may at times have
rustlike colour due to staining with haemosiderin. Some
coloured particulate material left in the wound may
persist and impart colour to the healed wound.
• 4. Deficient scar formation. This may occur due to
inadequate formation of granulation tissue.
• 5. Incisional hernia. A weak scar, especially after a
laparotomy, may be the site of bursting open of a
wound (wound dehiscence) or an incisional hernia.

35. 6. Hypertrophied scars and keloid formation. At times the scar
formed is excessive, ugly and painful. Excessive formation of
collagen in healing may result in keloid (claw-like) formation,
seen more commonly in Blacks.
Hypertrophied scars differ from keloid in that they are
confined to the borders of the initial wound while keloids
have tumourlike projection of connective tissue.
7. Excessive contraction. An exaggeration of wound contraction
may result in formation of contractures or cicatrisation e.g.
Dupuytren’s (palmar) contracture, plantar contracture and
Peyronie’s disease (contraction of the cavernous tissues of
penis).
8. Neoplasia. Rarely, scar may be the site for development of
carcinoma later e.g. squamous cell carcinoma in Marjolin’s
ulcer i.e. a scar following burns on the skin.

36. FACTORS INFLUENCING HEALING
A. LOCAL FACTORS:
1. Infection is the most important factor acting locally which delays the process of healing.
2. Poor blood supply to wound slows healing e.g. injuries to face heal quickly due to rich blood
supply while injury to leg with varicose ulcers having poor blood supply heals slowly.
3. Foreign bodies including sutures interfere with healing and cause intense inflammatory
reaction and infection.
4. Movement delays wound healing.
5. Exposure to ionising radiation delays granulation tissue formation.
6. Exposure to ultraviolet light facilitates healing.
7. Type, size and location of injury determines whether healing takes place by resolution or
organisation.

37. • B. SYSTEMIC FACTORS:
1. Age. Wound healing is rapid in young and
somewhatslow in aged and debilitated people due to
poor blood supply to the injured area in the latter.
2. Nutrition. Deficiency of constituents like protein,
vitamin C (scurvy) and zinc delays the wound healing.
3. Systemic infection delays wound healing.
4. Administration of glucocorticoids has anti-
inflammatory effect.
5. Uncontrolled diabetics are more prone to develop
infections and hence delay in healing.
6. Haematologic abnormalities like defect of neutrophil
functions (chemotaxis and phagocytosis), and
neutropenia and bleeding disorders slow the process of
wound healing.

39. HEALING AFTER SCALING AND
CURETTAGE
• Immediately- a blood clot fills the pocket area, which is
totally or partially devoid of epithelial lining.
• Hemorrhage is also present in the tissues with dilated
capillaries and abundant polymorphonuclear leukocytes
(PMNs), which appear on the wound surface.
• This is followed by a rapid proliferation of granulation
tissue with a decrease in the number of small blood vessels
as the tissue matures.

40. • Restoration and epithelialization of the sulcus generally
require 2 to 7 days.
• Restoration of the junctional epithelium occurs as early as
5 days after treatment.
• Immature collagen fibers appear within 21 days.

41. HEALING AFTER GINGIVECTOMY
• The initial response after gingivectomy is the formation of a
protective surface blood clot.
• The underlying tissue becomes acutely inflamed with
necrosis. The clot is then replaced by granulation tissue.
• In 24 hours, there is an increase in new connective tissue cells,
which are mainly angioblasts beneath the surface layer of
inflammation and necrotic tissue.
• By the third day, numerous young fibroblasts are located in
the area.
• The highly vascular granulation tissue grows coronally,
creating a new free gingival margin and sulcus.
• Capillaries derived from blood vessels of the periodontal
ligament migrate into the granulation tissue and within 2
weeks, they connect with the gingival vessels.

42. • After 12 to 24 hours, epithelial cells at the margins of the wound begin to migrate over the
granulation tissue, separating it from the contaminated surface layer of the clot.
• Epithelial activity at the margins reaches a peak in 24 to 36 hours.
• The new epithelial cells arise from the basal and deeper spinous layers of the epithelial
wound edge and migrate over the wound over a fibrin layer that is later resorbed and
replaced by a connective tissue bed.
• The epithelial cells advance by a tumbling action with the cells becoming fixed to the
substrate by hemidesmosomes and a new basement lamina.
After 5 to 14 days, surface epithelialization is generally complete.
• During the first 4 weeks after gingivectomy, keratinization is less than it was before surgery.
• Complete epithelial repair takes about 1 month.
• Vasodilation and vascularity begin to decrease after the fourth day of healing and appear to
be almost normal by the sixteenth day.
• Complete repair of the connective tissue takes about 7 weeks

43. HEALING AFTER FLAP SURGERY
• Immediately after suturing (up to 24 hours), a connection
between the flap and the tooth or bone surface is established
by a blood clot (which consists of a fibrin reticulum with
many polymorphonuclear leukocytes, erythrocytes, debris of
injured cells, and capillaries at the edge of the wound).
• Bacteria and an exudate or transudate also result from tissue
injury.
• One to 3 days after flap surgery, the space between the flap
and the tooth or bone is thinner and epithelial cells migrate
over the border of the flap, usually contacting the tooth at
this time.
• When the flap is closely adapted to the alveolar process,
there is minimal inflammatory response.

44. • One week after surgery, an epithelial attachment to the root
has been established by means of hemidesmosomes and a
basal lamina.
• The blood clot is replaced by granulation tissue derived from
the gingival connective tissue, the bone marrow, and the
periodontal ligament.
• Two weeks after surgery, collagen fibers begin to appear
parallel to the tooth surface.
• Union of the flap to the tooth is still weak because of the
presence of immature collagen fibers, although the clinical
aspect may be almost normal.
• One month after surgery, a fully epithelialized gingival crevice
with a well-defined epithelial attachment is present. There is a
beginning functional arrangement of the supracrestal fibers.

45. Full-thickness flaps
• Denudes the bone, result in a superficial bone necrosis
at 1 to 3 days.
• Osteoclastic resorption follows and reaches a peak at 4
to 6 days
• Declining thereafter.
Osteoplasty (thinning of the buccal bone)
• Results in areas of bone necrosis with reduction in
bone height, which is later remodeled by new bone
formation.
• Therefore, the final shape of the crest is determined
more by osseous remodeling than by surgical
reshaping.

46.  Harshmohan, Textbook of essential pathology for dental students-
3rd ed.
 Jan lindhe, Textbook of clinical periodontology & implant dentistry -
 F.A. Carranza, Textbook of clinical periodontology- 11th ed.
 Lariha¨kkinen,Veli-jukka Uitto & Hannularj Av, cell biology of gingival
wound healing, periodontology 2000, vol. 24, 2000, 127–152.

47. THANK YOU