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Wound healing
Contents
1. Introduction
2. Regeneration & repair
3. Healing by primary and secondary intension
4. Molecular biology of wo...
Introduction
A wound/Injury is
a disruption of
the anatomic
structure and
function in any
body part.
Wound
healing
Healing...
Periodontal wound healing
 A more complex situation presents itself when a
mucoperiosteal flap is apposed to an instrument...
Process of healing
 It involves 2 distinct processes :
 At times, both the processes take place
simultaneously
Regenerat...
Regeneration
 Natural renewal of a structure, produced by growth &
differentiation of new cells and intercellular substan...
Essential molecules for regeneration
Regeneration related to periodontal tissues
 Manifested by:
 Mitotic activity in the epithelium of the gingiva and conne...
Repair- “healing by scar”
 Replacement of one tissue with another tissue,
such as fibrous connective tissue, which may no...
Granulation tissue formation
 Each granule histologically corresponds to proliferation of new
small blood vessels which a...
Angiogenesis
 necessary to sustain newly formed granulation tissue
 proliferation of endothelial cells from the margins ...
fibrogenesis
 Emigration and proliferation of the fibroblasts at the site of injury
 Deposition of these cells which in ...
Wound contraction
 It starts after 2-3 days and the process is completed by the 14th day.
 Wound is reduced by 80% of it...
Repair related to periodontal tissues
 Simply restores the continuity of the diseased marginal
gingiva and re-establishes...
wound strength- extracellular matrix
 The wound is strengthened by proliferation of fibroblast and myofibroblast
which ge...
Healing by first intention
(Primary union)
 This is defined as healing of a wound which has the following
characteristics...
 Primary union involves the following sequence of events:
 Initial hemorrhage
 Acute inflammatory response- within 24 h...
The incised wound as well as suture
track on either side are filled with
blood clot and there is inflammatory
response fro...
Healing by secondary intention
(secondary union)
 This is defined as-
 Open wound with a large tissue defect, at times i...
 Secondary union consists of the following events :
 Initial hemorrhage
 Inflammatory process
 Epithelial changes
 Gr...
A. The open wound is filled with blood clot and there is inflammatory response at
the junction of viable tissue
B. Epithel...
Molecular biology of wound healing
1. The fibrin clot and inflammatory cells
 The important functions of the clot are:
 pl...
2. Re-epithelialization of wounds
 keratinocytes start moving into the defect about 24 hours after the
injury
 The kerat...
 At this edge, the cells will have to dissolve the hemidesmosome
attachment, downregulate the expression of α6β4, and upr...
3. Matrix degradation and the wound-cleaning
process
 creation of a migrating path for keratinocytes is achieved by
the d...
 MMP-1 degrades native collagens and aids cell migration by
destroying collagens I and III.
 MMP-9 (also known as gelati...
Connective tissue repair by:
 Activation of fibroblasts by platele granules
 Angiogenesis by VEGF and b-FGF
 Formation o...
 Wound repair involves phenotypic change of fibroblasts from
quiescent to proliferating cells, and subsequently to migrat...
Factors influencing healing
Complications of wound healing
Healing of oral wounds
 Oral wounds heals faster and with less scarring
than extra oral wounds
 It is mainly due to:
 f...
Role of saliva & GCF in oral wound healing
 Physico-chemical factors favoring healing are:
 appropriate PH
 ionic stren...
Lubrication of oral mucosa is beneficial for
wound healing
 Advantages of moist environment:
 Prevention of tissue dehyd...
Healing following scaling & root planing
 Numerous polymorphonuclear leucocytes can be seen between
residual epithelial c...
 In 4-5 days a new epithelial attachment may appear at bottom of
sulcus.
 Depending on the severity of inflammation & th...
Healing following curettage
 A blood clot forms between the root surface & the lateral wall
of the pocket, soon after the...
Healing after surgical gingivectomy
 Initial response- formation of a protective surface clot
 Clot is then replaced by ...
 By the 3rd day numerous young fibroblasts are located in
the area which start granulation tissue formation.
 The highly...
 After 5-14 days: surface epitheliazation is complete
 During first 4 weeks: keratinization is less than it was
before s...
Healing following electrosurgical gingivectomy
 There appears to be little difference in the results obtained after
shall...
Healing following depigmentation of gingiva
Healing after surgical depigmentation:
 After surgery it was found necessary ...
Healing following depigmentation by laser:
 During lasing gingiva gets covered with a yellowish layer, that could
be easi...
Healing following flap surgery
 Immediately response- clot formation
 At edge of flap numerous capillaries are seen
 1-...
 The blood clot is replaced by granulation tissue proliferating from
the gingival connective tissue, alveolar bone and pe...
In cases where Mucoperiosteal flap…
 superficial bone necrosis have been observed during first 3 days
 Osteoclastic Reso...
Healing following osseous resection
 Elevation of Mucoperiosteal Flap results in
temporary loss of nutrient supply to the...
Healing after implant placement
 The interface area consists of bone, marrow tissue, and a hematoma
mixed with bone fragm...
Stages of healing of implants
a. Woven Bone Formation: When bone matrix is exposed to extra-cellular
fluid, non-collagenou...
Use of lasers in wound healing
 Lasers employing low-level energy have been claimed to produce
a positive effect on the b...
conclusion
 Current scientific evidence points to the presence of:
1. cells originating from the periodontal ligament,
2....
 Wound healing is achieved by a series of coordinated efforts by
inflammatory cells, keratinocytes, fibroblasts and endot...
References
 Harshmohan, Textbook of essential pathology for dental students-3rd ed.
 Jan lindhe, Textbook of clinical pe...
Wound healing [including healing after periodontal therapy]
Wound healing [including healing after periodontal therapy]
Wound healing [including healing after periodontal therapy]
Wound healing [including healing after periodontal therapy]
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Wound healing [including healing after periodontal therapy]

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

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Wound healing [including healing after periodontal therapy]

  1. 1. Wound healing
  2. 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. 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. 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. 5. Process of healing  It involves 2 distinct processes :  At times, both the processes take place simultaneously Regeneration Repair
  6. 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.
  7. 7. Essential molecules for regeneration
  8. 8. 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.
  9. 9. 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
  10. 10. 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)
  11. 11. Angiogenesis  necessary to sustain newly formed granulation tissue  proliferation of endothelial cells from the margins of the severed vessels
  12. 12. 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.
  13. 13. 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
  14. 14. 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.
  15. 15. 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
  16. 16. 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
  17. 17.  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
  18. 18. 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
  19. 19. 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
  20. 20.  Secondary union consists of the following events :  Initial hemorrhage  Inflammatory process  Epithelial changes  Granulation tissue formation  Wound contraction
  21. 21. 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
  22. 22. 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.
  23. 23. 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
  24. 24.  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.
  25. 25. 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
  26. 26.  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
  27. 27. 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.
  28. 28.  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
  29. 29. Factors influencing healing
  30. 30. Complications of wound healing
  31. 31. 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
  32. 32. 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
  33. 33. 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
  34. 34. 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.
  35. 35.  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.
  36. 36. 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
  37. 37. 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
  38. 38.  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
  39. 39.  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.
  40. 40. 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.
  41. 41. 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.
  42. 42. 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
  43. 43. 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.
  44. 44.  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.
  45. 45. 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.
  46. 46. 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
  47. 47. 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.
  48. 48. 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.
  49. 49. 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.
  50. 50. 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.
  51. 51.  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.
  52. 52. 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.

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