Basic about wound healing mechanism and details about healing after various periodontal therapies.

1. Wound healing

2. Contents
1. Introduction
2. Regeneration & repair
3. Healing by primary and secondary intension
4. Molecular biology of wound healing
5. Factors influencing/ complications of wound healing
6. Healing of oral wounds
7. Role of saliva and GCF in wound healing
8. Wound healing following various periodontal therapies
9. Use of lasers in wound healing
10. conclusion

3. Introduction
A wound/Injury is
a disruption of
the anatomic
structure and
function in any
body part.
Wound
healing
Healing on the other
hand is a cell response
to injury in an attempt
to restore the normal
structure and function.

4. Periodontal wound healing
 A more complex situation presents itself when a
mucoperiosteal flap is apposed to an instrumented root surface
deprived of its periodontal attachment.
 In this case, the wound margins are not two opposing vascular
gingival margins but comprise the rigid nonvascular
mineralized tooth surface, on the one hand, and the connective
tissue and epithelium of the gingival flap, on the other hand.

5. Process of healing
 It involves 2 distinct processes :
 At times, both the processes take place
simultaneously
Regeneration Repair

6. Regeneration
 Natural renewal of a structure, produced by growth &
differentiation of new cells and intercellular substances to
form new tissues or parts which function the same as
original tissues.
 Growth from the same type of tissue that has been destroyed
or from its precursors.
 Periodontal tissues are limited in their regenerative
capacity.

8. Essential molecules for regeneration

9. Regeneration related to periodontal tissues
 Manifested by:
 Mitotic activity in the epithelium of the gingiva and connective tissue
of PDL
 Bone remodelling
 Continuous deposition of cementum
 Most gingival and periodontal diseases are chronic inflammatory
process and, as such are, healing lesions.

10. Repair- “healing by scar”
 Replacement of one tissue with another tissue,
such as fibrous connective tissue, which may not function the
same as the tissue replaced.
 Two processes are involved in the repair:
1. Granulation tissue formation
2. Contraction of wounds

11. Granulation tissue formation
 Each granule histologically corresponds to proliferation of new
small blood vessels which are slightly lifted on the surface by a
thin covering of fibroblasts and young collagen
Granulation tissue
formation
Phase of
inflammation
Phase of clearance
Phase of ingrowth
of granulation
tissue
Angiogenesis
(neovascularization)
Formation of
fibrous tissue
(fibrogenesis)

12. Angiogenesis
 necessary to sustain newly formed granulation tissue
 proliferation of endothelial cells from the margins of the severed
vessels

13. fibrogenesis
 Emigration and proliferation of the fibroblasts at the site of injury
 Deposition of these cells which in turn increases collagen synthesis
 As the maturation proceeds: there is an increase in the collagen, and a
decrease in the fibroblasts and blood vessels .
 This leads to the formation of scar know as CICATRISATION.

14. Wound contraction
 It starts after 2-3 days and the process is completed by the 14th day.
 Wound is reduced by 80% of its original size which helps in rapid
healing since lesser surface area of the injured tissue has to be
replaced.
Mechanisms
of wound
contraction
dehydration
myofibroblasts
Contraction of
collagen

15. Repair related to periodontal tissues
 Simply restores the continuity of the diseased marginal
gingiva and re-establishes a normal gingival sulcus at the
same level on the roots as the base of the pre-existing
periodontal pocket.
 Arrests bone destruction but does not result in gain of
gingival attachment or bone height.

16. wound strength- extracellular matrix
 The wound is strengthened by proliferation of fibroblast and myofibroblast
which get structural support from the extracellular matrix
 ECM has five main components:
1. collagen
2. adhesive glycoprotein
fibronectin - plasma/ tissue type
tenascin or cytotactin
thrombospondin
3. basement membrane
4. elastic fibres
5. proteoglycans

17. Healing by first intention
(Primary union)
 This is defined as healing of a wound which has the following
characteristics:
 Clean and uninfected
 Surgically incised
 Without much loss of cells and tissue
 Edges of wound are approximated by surgical suture

18.  Primary union involves the following sequence of events:
 Initial hemorrhage
 Acute inflammatory response- within 24 hours
 Epithelial changes- completes by 48 hours
 Organization of fibroblasts- starts around 3rd day
 Wound maturation- starts after 1 week and completes
around 4 weeks

19. The incised wound as well as suture
track on either side are filled with
blood clot and there is inflammatory
response from the margins
spurs of epidermal cells migrate along the
incised margin on either side as well as round the
suture track, formation of granulation tissue also
begins from below.
removal of sutures at around 7th day
result in scar tissue at the sites of
incision and suture track

21. Healing by secondary intention
(secondary union)
 This is defined as-
 Open wound with a large tissue defect, at times infected
 Extensive loss of cells and tissues
 Not approximated by sutures, but is left open

22.  Secondary union consists of the following events :
 Initial hemorrhage
 Inflammatory process
 Epithelial changes
 Granulation tissue formation
 Wound contraction

23. 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
A B C

24. Molecular biology of wound healing
1. The fibrin clot and inflammatory cells
 The important functions of the clot are:
 plugs the cut blood vessels and also serves to protect the
denuded tissues temporarily.
 reservoir of growth factors and cytokines that are released by the
degranulation of activated platelets and serving as a provisional
matrix for cell migration and might be providing the start signals
for wound repair.

25. 2. Re-epithelialization of wounds
 keratinocytes start moving into the defect about 24 hours after the
injury
 The keratinocytes use receptors on their surface, known as integrins
to bind to laminin in the basal lamina.
 Integrins are a family of cell adhesion receptors that mediate cell
surface interactions with extracellular matrix and in some cases
with other cells

26.  At this edge, the cells will have to dissolve the hemidesmosome
attachment, downregulate the expression of α6β4, and upregulate
integrin receptors α5β1, αVβ6 and αVβ5 that are suitable for adhesion
to provisional matrix components.
 epidermal growth factor
 transforming growth factor-α
 heparin-binding epidermal growth factor and
 keratinocyte growth factor are involved in stimulating the
proliferation of the epithelial cells here.

27. 3. Matrix degradation and the wound-cleaning
process
 creation of a migrating path for keratinocytes is achieved by
the dissolution of the fibrin barrier by the enzyme plasmin
that is derived from the activation of plasminogen in the clot.
 The two activators, tissue-type plasminogen activator and
urokinase-type plasminogen activator along with its receptor,
are upregulated in the migrating keratinocytes

28.  MMP-1 degrades native collagens and aids cell migration by
destroying collagens I and III.
 MMP-9 (also known as gelatinase B) can cleave the collagen in basal
lamina (type IV) and the collagen that forms the anchoring fibrils
(type VII)
 MMP10 (also known as stromelysin-2) is also expressed in wounds
and is thought to have a wide spectrum of substrate specificity for
collagen

29. Connective tissue repair by:
 Activation of fibroblasts by platele granules
 Angiogenesis by VEGF and b-FGF
 Formation of Granulation tissue by TGF, PDGF, FGF and EGF
 contraction of the wound by myofibroblasts.

30.  Wound repair involves phenotypic change of fibroblasts from
quiescent to proliferating cells, and subsequently to migratory, and
then to stationary matrix producing and contractile cells.
 In the connective tissue, fibroblasts are surrounded by a matrix
that contains collagen and cellular fibronectin as the major
components. Consequently, quiescent fibroblasts express collagen
receptors α1β1 and α2β1 and the major fibronectin receptor α5β1
integrin which they use for adhesion to the matrix

31. Factors influencing healing

33. Complications of wound healing

34. Healing of oral wounds
 Oral wounds heals faster and with less scarring
than extra oral wounds
 It is mainly due to:
 factors in saliva
 specific microflora of the oral cavity
 resemblance of fetal fibroblast with gingival
fibroblast

35. Role of saliva & GCF in oral wound healing
 Physico-chemical factors favoring healing are:
 appropriate PH
 ionic strength
 calcium and magnesium ions
 Saliva has an efficient capacity to reduce redox activity
caused by transitional metal ions and inhibit the
production of free radicals that may be beneficial for the
healing process

36. Lubrication of oral mucosa is beneficial for
wound healing
 Advantages of moist environment:
 Prevention of tissue dehydration and cell death
 accelerated angiogenesis
 incremental breakdown of fibrin and tissue debris
 Presence of growth factor – produced by saliva

38. Healing following scaling & root planing
 Numerous polymorphonuclear leucocytes can be seen between
residual epithelial cells & crevicular surface in about 2 hrs
 There is dilation of blood vessels, oedema & necrosis in the
lateral wall of the pocket
 24 hrs after scaling a widespread infiltration of inflammatory
cells and migration of keratinocytes have been observed, in
all areas of the remaining epithelium& in 2 days the entire
pocket is epithlialized.

39.  In 4-5 days a new epithelial attachment may appear at bottom of
sulcus.
 Depending on the severity of inflammation & the depth of
the gingival crevice, complete epithelial healing occurs in 1-2
weeks
 connective tissue repair by Immature collagen fibers occur within
21days.
 healing occurs with the formation of a long thin junctional
epithelium with no connective tissue attachment.

40. Healing following curettage
 A blood clot forms between the root surface & the lateral wall
of the pocket, soon after the curettage
 Large number of polymorphonuclear leucocytes after the procedure
 rapid proliferation of granulation tissue
 Epithelisation of the inner surface of the lateral wall is completed
in 2-7 days
 The junctional epithelium is also formed in about 5 days

41. Healing after surgical gingivectomy
 Initial response- formation of a protective surface clot
 Clot is then replaced by granulation tissue
 By 24 hours there is an increase in new connective tissue cells,
mainly angioblasts just beneath the surface layer of inflammation and
necrosis

42.  By the 3rd day numerous young fibroblasts are located in
the area which start granulation tissue formation.
 The highly vascular granulation tissue grows coronally,
creating a new free gingival margin and sulcus
 Capillaries derived from the blood vessels of the
periodontal ligament migrate in to the granulation tissue
and within 2 weeks they connect with gingiva vessels

43.  After 5-14 days: surface epitheliazation is complete
 During first 4 weeks: keratinization is less than it was
before surgery
 Complete epithelial repair takes 1 month.
 Complete repair of the C.T. takes about 7 weeks
 Flow of GCF is initially increased after gingivectomy and
diminishes as healing progresses.

44. Healing following electrosurgical gingivectomy
 There appears to be little difference in the results obtained after
shallow gingival resection with electrosurgery and that with
periodontal knives.
 when used for deep resection close to bone, electrosurgery can
produce gingival recession, bone necrosis and sequestration, loss of
bone height, furcation exposure, and tooth mobility, which do not
occur with the use of periodontal knives.

45. Healing following depigmentation of gingiva
Healing after surgical depigmentation:
 After surgery it was found necessary to cover the exposed lamina propria
with periodontal packs for 7 to 10 days.
 After 6 weeks the attached gingiva regenerated by only a delicate scar
present. The newly formed gingiva was clinically non-pigmented.
Healing following cryosurgical depigmentation:
 At 2nd to 3rd day: superficial necrosis becomes apparent and a whitish
slough could be separated from the underlying tissue, leaving a clean
pink surface.
 In 1-2 weeks: normal gingiva
 In 3-4 weeks: keratinization completed.
 No postoperative pain, hemorrhage, infection or scarring seen in patients.

46. Healing following depigmentation by laser:
 During lasing gingiva gets covered with a yellowish layer, that could
be easily removed by a wet gauze.
 After 1-2 weeks: completion of re-epithelization.
 At 4th week: gingiva is similar to normal untreated gingiva i.e.,
lacking melanin pigmentation completely

47. Healing following flap surgery
 Immediately response- clot formation
 At edge of flap numerous capillaries are seen
 1-3days after surgery space between flap & tooth surface & bone
appears reduced & the epithelial cells along border of the flap start
migrating
 By 1 week after surgery
epithelial cells have migrated & established an attachment to root
surface by means of hemidesmosomes.

48.  The blood clot is replaced by granulation tissue proliferating from
the gingival connective tissue, alveolar bone and periodontal ligament
 By 2nd week collagen fibers begins to appear. Collagen fibers gets
arranged parallel to root surface rather than at right angles. The
attachment between soft tissue & tooth surface is weak
 By end of one month following surgery the epithelial attachment is
well formed & the gingival crevice is also well epithealised
 There is beginning functional arrangement of supracrestal fibres.

49. In cases where Mucoperiosteal flap…
 superficial bone necrosis have been observed during first 3 days
 Osteoclastic Resorption occurs in that area which reaches its peak at
4-6 days
 Osteoblastic Remodelling occurs subsequently
 Loss of alveolar bone height by about 1 mm may be expected after
healing.

50. Healing following osseous resection
 Elevation of Mucoperiosteal Flap results in
temporary loss of nutrient supply to the bone
 In addition, surgical resection of bone also
contributes to necrosis of the alveolar crest & osteoclastic resorption
of the bone takes place initially
 The initial loss in bone height is compensated to some extent by the
osteoblastic repair and remodelling.
 Thus final loss in bone height is clinically insignificant
 Osteoblastic activity is even seen after 1 yr. post-operatively

51. Healing after implant placement
 The interface area consists of bone, marrow tissue, and a hematoma
mixed with bone fragments from the drilling process.
 In the early phase of healing, woven bone is formed by osteoblasts at
the surfaces of trabecular and endosteal cortical bone surrounding the
implant.
 In the late phases of healing, lamellar bone replaces woven bone in a
process of creeping substitution.

52. Stages of healing of implants
a. Woven Bone Formation: When bone matrix is exposed to extra-cellular
fluid, non-collagenous proteins & growth factors are set free & initiate
repair.
Woven bone formation dominates the first4-6 weeks
b. Lamellar Bone Formation: From 2nd month post-operatively the
microscopic structure of bone changes to lamellar bone
c. Bone Remodelling: It begins around 3rd month post-operatively.
Initially rapid remodeling occurs which slows down & continues
for rest of the life
Thus complete healing probably takes longer than 3 to 6 months.

53. Use of lasers in wound healing
 Lasers employing low-level energy have been claimed to produce
a positive effect on the biological and bio-chemical processes of
wound re-constitution.
 Dermatologic investigations have demonstrated more rapid
epithelialization, enhanced neovascularization, and increased
production of collagen by fibroblasts in vivo
 Ultimately, accelerated wound healing, reduced pain and enhanced
neural regeneration.

54. conclusion
 Current scientific evidence points to the presence of:
1. cells originating from the periodontal ligament,
2. wound stability,
3. space provision
4. primary intention healing, as fundamental biologic and clinical
factors that must be met to obtain periodontal regeneration.

55.  Wound healing is achieved by a series of coordinated efforts by
inflammatory cells, keratinocytes, fibroblasts and endothelial
cells responding to a complex array of signals.
 Future research will have to be directed towards understanding
in more detail the molecular mechanisms of differential gene
expression in healing wounds.

56. References
 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- 10th ed.
 Lariha¨kkinen,Veli-jukka Uitto & Hannularj Av, cell biology of gingival
wound healing, periodontology 2000, vol. 24, 2000, 127–152.
 Guy A. Catone, Edward Halusic. Photobiology of lasers in oral and
maxillofacial surgery. In: Guy A. Catone, Charles C. Alling. Lasers
applications in oral and maxillofacial surgery. USA: W.B. Saunders
company, 1997.