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THE ABILITY TO HEAL IS INBUILT
IN OUR PHYSIOLOGY. WE ONLY
HELP BODY TO HEAL ITSELF AND
REMOVE ANY OBSTACLES IN THE
PATH OF HEALING.
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Wound Healing and Repair
PRESENTED BY :-
ADITI CHANDEL
MDS 1ST YEAR
DEPARTMENT OF PERIODONTOLOGY
AND ORAL IMPLANTOLOGY 2/69
GUIDED BY :
DR. BALJEET SINGH
(PROFESSOR)
DEPARTMENT OF PERIODONTOLOGY
AND ORAL IMPLANTOLOGY
CONTENTS
• DEFINITION OF HEALING
• TYPES OF HEALING
• PHASES OF WOUND HEALING
• FACTORS INFLUENCING WOUND HEALING
• COMPLICATIONS OF WOUND HEALING
• FRACTURE HEALING
• PERIODONTOLOGY IMPLICATIONS
• HEALING IN IMPLANTS
• ENDODONTIC IMPLICATIONS
• HEALING AFTER EXTRACTION OF TOOTH
• HEALING OF REIMPLANTED TOOTH
• REMODELLING OF BONE IN ORTHODONTICS
• HEALING IN PATIENTS ON CHEMOTHERAPY/ RADIATION
THERAPY
• RECENT TRENDS IN MANAGEMENT OF WOUNDS
• CONCLUSION
• REFERENCES
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HEALING
HEALING IS THE BODY RESPONSE TO INJURY IN AN ATTEMPT TO RESTORE
NORMAL STRUCTURE AND FUNCTION.
-
WOUND HEALING IS A PRIMARY SURVIVAL MECHANISM AND IS A PROTECTIVE
FUNCTION OF THE BODY THAT FOCUSES ON QUICK RECOVERY.
-WONG ET AL, 2013
HEALING
INVOLVES
REGENERATION REPAIR
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5 / 69
Robbins and cotran basic pathology 9th ed
REGENERATION
• WHEN HEALING TAKES PLACE BY PROLIFERATION OF PARENCHYMAL CELLS AND
IT USUALLY RESULTS IN COMPLETE RESTORATION OF THE ORIGINAL TISSUES
 PERIODONTAL REGENERATION is defined as the restoration of lost periodontium or
supporting tissues and includes formation of new alveolar bone, new cementum and new
periodontal ligament. Wang HL et al in 2005
THE FACTORS WHICH CONTROL HEALING AND REPAIR ARE COMPLEX AND THEY
INCLUDE THE PRODUCTION OF VARIETY OF GROWTH FACTORS:
EPIDERMAL GROWTH FACTORS
FIBROBLAST GROWTH FACTORS
ENDOTHELIAL GROWTH FACTOR
PLATELET DERIVED GROWTH FACTOR
TRANSFORMING GROWTH FACTOR- B
6 / 69
ESSENTIAL PATHOLOGY BY HARSHMOHAN, 4TH EDITION
TISSUE PROLIFERATION ACTIVITY
LABILE CELLS
STABLE CELLS
PERMANENT
CELLS
• CONTINUE TO MULTIPLY THROUGHOUT LIFE UNDER NORMAL
PHYSIOLOGIC CONDITIONS.
• E.G. SURFACE EPITHELIAL CELLS OF THE EPIDERMIS,
HAEMOPOIETIC CELLS OF BONE MARROW ETC.
• DECREASE OR LOSE THEIR ABILITY TO PROLIFERATE AFTER
ADOLESCENCE.
• CELLS FROM THESE TISSUE CAN UNDERGO RAPID DIVISION IN RESPONSE
TO STIMULI.
• E.G. PARENCHYMAL CELLS OF LIVER AND KIDNEY, BONE AND CARTILAGE
CELLS, FIBROBLASTS ETC.
• CANNOT UNDERGO MITOTIC DIVISION IN THE
POSTNATAL LIFE.
• E.G. NEURONS AND CARDIAC MUSCLE CELLS.
7 / 69
ESSENTIAL PATHOLOGY BY HARSHMOHAN, 4TH EDITION
CELL CYCLE
8 / 69
REPAIR
WHEN HEALING TAKES PLACE BY
PROLIFERATION OF CONNECTIVE TISSUE
ELEMENTS RESULTING IN FIBROSIS AND
SCARRING.
REPAIR IS THE REPLACEMENT OF INJURED
TISSUES BY THE FIBROUS TISSUE.
GRANULATIO
-N TISSUE
FORMATION
CONTRACTI-
-ON OF
WOUNDS
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ROBBINS AND COTRAN, PATHOLOGIC BASIS OF DISEASE, 7TH ED.
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 Granulation Tissue formation
• GRANULATION TISSUE IS THE HALLMARK OF HEALING.
• GRANULATION TISSUE PROGRESSIVELY INVADES THE SITE OF
INJURY
• THE TERM GRANULATION TISSUE DERIVES ITS NAME FROM ITS
PINK, SOFT, GRANULAR APPEARANCE OF TISSUE.
PHASE OF
INFLAMMATION
PHASE OF
CLEARANCE
PHASE OF INGROWTH
OF GRANULATION
TISSUE
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ROBBINS AND COTRAN, PATHOLOGIC BASIS OF DISEASE, 7TH ED.
1: INFLAMMATION:
BLOOD CLOTS, EXUDATION OF PLASMA,
NEUTROPHILS, MONOCYTES WITHIN 24 HOURS.
2: CLEARANCE:
PROTEOLYTIC ENZYMES LIBERATED FROM
NEUTROHILS, AUTOLYTIC ENZYMES FROM DEAD TISSUE
CELLS, PHAGOCYTIC ACTIVITY OF MACROPHAGES.
3: INGROWTH OF GRANULATION TISSUE:
ANGIOGENESIS
FIBROGENESIS
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ROBBINS AND COTRAN, PATHOLOGIC BASIS OF DISEASE, 7TH ED.
-FORMATION OF NEW BLOOD VESSELS AT THE SITE
OF INJURY BY PROLIFERATION OF ENDOTHELIAL
CELLS FROM MARGINS OF SEVERED BLOOD VESSELS.
-THE PROCESS OF ANGIOGENESIS IS STIMULATED
WITH PROTEOLYTIC DESTRUCTION OF BASEMENT
MEMBRANE.
-VARIOUS FACTORS INFLUENCING ANGIOGENESIS:
VASCULAR ENDOTHELIAL GROWTH FACTOR
(VEGF), PLATELET DERIVED GROWTH FACTOR,
TRANSFORMING GROWTH FACTOR-B, BASIC
FIBROBLAST GROWTH FACTOR (bFGF).
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ANGIOGENESIS
ROBBINS AND COTRAN, PATHOLOGIC BASIS OF DISEASE, 7TH ED.
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IN THE NEWLY
FORMED BLOOD
VESSELS,
FIBROBLASTS
ORIGINATE FROM
FIBROCYTES AS WELL
AS THE MITOTIC
DIVISION OF
FIBROBLASTS.
A
COLLAGEN FIBRILS
BEGIN TO APPEAR BY
6TH DAY.
B
AS MATURATION
PROCEEDS, MORE
COLLAGEN IS FORMED
WHERE AS THE
NUMBER OF
FIBROBLASTS
DECREASES.
C
THERE IS FORMATION
OF INACTIVE
LOOKING SCAR
KNOWN AS
CICATRISATION
D
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FIBROGENESIS
ROBBINS AND COTRAN, PATHOLOGIC BASIS OF DISEASE, 7TH ED.
 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.
MECHANISM OF
WOUND
CONTRACTION
CONTRACTION OF COLLAGEN
DEHYDRATION
MYOFIBROBLASTS
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DAS. CONCISE TEXTBOOK OF SURGERY, 3RD EDITION
WOUND HEALING
A WOUND IS A BREAK IN THE INTEGRITY OF THE
SKIN OR TISSUES OFTEN WHICH MAY BE
ASSOCIATED WITH DISRUPTION OF THE
STRUCTURE AND FUNCTION.
( SRB 4TH EDITION)
A WOUND IS A CUT OR BREAK IN THE
CONTINUITY OF ANY TISSUE, CAUSED BY INJURY
OR OPERATION.
( BAILLIERE’S 23RD EDITION )
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JOURNAL OF BURNS AND WOUNDS (http://www.ncbi.nlm.nih.gov/pmc/journals/211/)
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ROBBINS AND COTRAN, PATHOLOGIC BASIS OF DISEASE, 7TH ED.
Growth Factors and Cytokines Affecting Various Steps in
Wound Healing
Monocyte chemotaxis PDGF, FGF, TGF-ß
Fibroblast migration PDGF, EGF, FGF, TGF-ß, TNF,
IL-1
Fibroblast proliferation PDGF, EGF, FGF, TNF
Angiogenesis VEGF, Ang, FGF
Collagen synthesis TGF-ß, PDGF
Collagenase secretion PDGF, EGF, FGF, TNF, TGF-ß
inhibits
PDGF- platelet-derived growth factor
FGF- fibroblast growth factor
TGF- transforming growth factor
EGF- epidermal growth factor
IL- interleukin
TNF- tumor necrosis factor
VEGF- vascular endothelial growth factor
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ROBBINS AND COTRAN, PATHOLOGIC BASIS OF DISEASE, 7TH ED.
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TYPES OF WOUND HEALING
WOUND HEALING CAN BE ACCOMPLISHED IN ONE OF THE
FOLLOWING WAYS:
• HEALING BY FIRST INTENTION
(PRIMARY UNION)
• HEALING BY SECOND INTENTION
(SECONDARY UNION)
• HEALING BY TERTIARY INTENTION
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ESSENTIAL PATHOLOGY BY HARSHMOHAN, 4TH EDITION
Healing by First Intention (Primary Union)
• CLEAN INCISED WOUND OR SURGICAL UNINFECTED WOUND.
• MORE EPITHELIAL REGENERATION THAN FIBROSIS.
• WOUND HEALS RAPIDLY WITH COMPLETE CLOSURE WITHOUT MUCH
LOSS OF CELLS AND TISSUE.
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ESSENTIAL PATHOLOGY BY HARSHMOHAN, 4TH EDITION
EVENTS IN PRIMARY UNION
• OCCURS WITHIN 24 HOURS.
• APPEARANCE OF POLYMORPHS, WHICH ARE REPLACED BY MACROPHAGES ON
3rd DAY.
INITIAL HAEMORRHAGE
ACUTE INFLAMMATORY
RESPONSE
EPITHELIAL CHANGES
ORGANISATION
SUTURE TRACKS
• BLOOD CLOTS IN THE SPACE BETWEEN APPROXIMATED INCISED WOUND SURFACES.
• IT SEALS THE WOUND AGAINST DEHYDRATION AND INFECTION.
•PROLIFERATION AND MIGRATION OF BASAL CELLS OF EPIDERMIS AS EPITHELIAL
SPURS.
•SCAB FORMATION SEPERATING UNDERLYING VIABLE DERMIS FROM OVERLYING
NECROTIC MATERIAL AND CLOT.
•BY 5TH DAY MULTILAYERED NEW EPIDERMIS IS FORMED
•BY 3RD DAY FIBROBLAST INVADE WOUND AREA .
•BY 5TH DAY NEW COLLAGEN FIBRILS IS FORMED.
•IN 4 WEEKS SCAR TISSUE WITH SCANTY CELLULAR AND VASCULAR ELEMENTS.
•FILLING SPACE WITH HAEMORRHAGE, INFLAMMATORY CELL
REACTION, FORMATION OF YOUNG COLLAGEN.
•STITCH ABSCESS, IMPLANTATION OR EPIDERMAL CYSTS.
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BOYD’S TEXTBOOK OF PATHOLOGY 9TH EDITION
Suture Classification
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Suture materials can be described in three ways, according to
their structure, source and fate within the body:-
•Structure – Monofilament/Braided/Barbed
• Source – Natural or Synthetic
• Fate – Absorbable or Non-absorbable
HEALING BY SECOND INTENTION (SECONDARY UNION)
• OPEN WOUND WITH LARGE TISSUE DEFECT, AT TIMES
INFECTED.
• EXTENSIVE LOSS OF CELLS AND TISSUES.
• WOUND IS NOT APPROXIMATED BY SURGICAL SUTURES BUT
IS LEFT OPEN.
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ESSENTIAL PATHOLOGY BY HARSHMOHAN, 4TH EDITION
EVENTS IN SECONDARY UNION
INITIAL HAEMORRHAGE
INFLAMMATION
EPITHELIAL CHANGES
GRANULATION TISSUE
WOUND CONTRACTION
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BOYD’S TEXTBOOK OF PATHOLOGY 9TH EDITION
HEALING BY TERTIARY INTENTION
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Tertiary wound healing, or healing by delayed primary closure, occurs when
there is a need to delay the wound-closing process. This occurs when the
process of secondary intention is intentionally interrupted and the wound is
mechanically closed. This usually occurs after granulation tissue has formed.
FEATURES PRIMARY SECONDARY
CLEANLINESS CLEAN NOT CLEAN
INFECTION NOT INFECTED INFECTED
MARGINS SURGICALLY CLEAN IRREGULAR
SUTURES USED NOT USED
HEALING SMALL GRANULATION
TISSUE
LARGE GRANULATION
TISSUE
OUT COME LINEAR SCAR IRREGULAR WOUND
COMPLICATION NOT FREQUENT FREQUENT
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DAS. CONCISE TEXTBOOK OF SURGERY, 3RD EDITION
EXTRACELLULAR MATRIX : WOUND
STRENGTH
• THE ECM IS A STRUCTURAL SUPPORT NETWORK MADE
UP OF DIVERSE PROTEINS, SUGARS AND OTHER
COMPONENTS.
• IT INFLUENCES WIDE NUMBER OF CELLULAR
PROCESSES INCLUDING MIGRATION, WOUND HEALING
AND DIFFERENTIATION.
• ECM COMPRISES OF:
(1) FIBROUS STRUCTURAL PROTEIN – COLLAGENS AND
ELASTIN
(2) ADHESIVE GLYCOPROTEIN
(3) PROTEOGLYCANS AND HYALURONIC ACID
• THESE MACROMOLECULES ARE PRESENT IN
INTERCELLULAR JUNCTIONS AND CELL SURFACES
AND FORM TWO GENERAL ORGANIZATIONS:
 INTERSTITIAL MATRIX
 BASEMENT MEMBRANE 29 / 69
ESSENTIAL PATHOLOGY BY HARSHMOHAN, 4TH EDITION
 COLLAGEN:
- TYPE I: FOUND IN SKIN, BONE, AND
MATURE SCARS.
- TYPE II: CARTILAGE.
- TYPE III: ABUNDANT IN EMBRYONIC AND
PLIABLE TISSUES. FIRST COLLAGEN
DEPOSITED IN WOUND HEALING.
- TYPE IV: BASEMENT MEMBRANES AND
ASSOCIATED WITH LAMININ AND OTHER
MATRIX COMPONENTS.
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ROBBINS AND COTRAN, PATHOLOGIC BASIS OF DISEASE, 7TH ED.
 COLLAGEN PROVIDES TENSILE
STRENGTH, WHEREAS ELASTIC FIBERS
PROVIDE RECOIL, AND THUS TEND TO BE
FOUND IN THE AORTA, SMALLER
ARTERIES, SKIN, LUNG, AND UTERUS.
ELASTIC FIBERS
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ESSENTIAL PATHOLOGY BY HARSHMOHAN, 4TH EDITION
STRUCTURAL GLYCOPROTEIN
• FIBRONECTIN: (NECTERE, TO BIND)
• BINDS TO COLLAGENS, PROTEOGLYCANS,
FIBRINOGEN, FIBRIN, CELL SURFACES,
BACTERIA AND DNA.
• ONE OF THE FIRST STRUCTURAL MOLECULES
DEPOSITED DURING EMBRYONIC
DEVELOPMENT.
• FOUND IN TISSUE AND PLASMA.
• SYNTHESIZED BY HEPATOCYTES.
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ESSENTIAL PATHOLOGY BY HARSHMOHAN, 4TH EDITION
• PROTEOGLYCANS:
• USED TO BE CALLED MUCOPOLYSACCHARIDES, BUT ARE NOW
REFFERED TO AS GLYCOSAMINOGLYCANS.
• HIGHLY HYDROPHILIC, AND FORM HYDRATED GELS, EVEN AT LOW
CONCENTRATION.
• SEEN IN EARLY WOUND HEALING
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ESSENTIAL PATHOLOGY BY HARSHMOHAN, 4TH EDITION
FACTORS INFLUENCING HEALING
SYSTEMIC LOCAL
NUTRITION :- e.g. Protein and Vit.C
deficiency inhibit collagen Synthesis and
Retard Healing .
Infection- cause delay in wound healing.
Circulatory Status:- inadequate blood
supply caused by arteriosclerosis or
venous abnormalities also impair healing.
Mechanical factors:- such as early motion
of wounds cause delay in healing.
Hormones:- such as glucocorticoids will
inhibit collagen synthesis.
Foreign bodies:- ununecessary sutures or
fragments of steel, glass or even bone can
impede healing.
Systemic Conditions Retarding Healing:
AIDS/HIVinfection,Menopause,
Connective Tissue Disorder such as
EHLER DANLOS SYNDROME, CVS
Disease etc
Size, location and type of wound:- wound
in richly vascularized areas heals faster ,
small wounds produced intentionally
heals faster than larger ones caused by
trauma
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ROBBINS AND COTRAN, PATHOLOGIC BASIS OF
DISEASE, 7TH ED.
SYSTEMIC MEDICATION AFFECTING
WOUND HEALING
- BISPHOSPHONATES: E.g. Etidronate,
Alendronate, Pamidronate
- GLUCOCORTICOIDS: E.g. Prednisone,
Beclomethasone
- NSAIDS: E.g. Diclofenac, Naproxen, Ibuprofen
- CYCLO OXYGENASE - 2 INHIBITORS: E.g.
Celecoxib, Rofecoxib
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TEXTBOOK OF ESSENTIAL PATHOLOGY BY HARSHMOHAN, 4TH EDITION
COMPLICATIONS OF WOUND
HEALING
• INFECTION
• IMPLANTATION CYST (EPIDERMAL)
• PIGMENTATION
• DEFICIENT SCAR FORMATION
• INCISIONAL HERNIA
• HYPERTROPHIED SCARS AND
KELOID FORMATION
• EXCESSIVE CONTRACTION
• NEOPLASIA
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COHEN’S , 11TH EDITION
FRACTURE HEALING
• PRIMARY UNION OF FRACTURE
• SECONDARY UNION OF FRACTURE
HEMATOMA
INGROWTH OF
GRANULATION TISSUE
REMODELLING
CALLUS COMPOSED OF
WOVEN BONE AND
CARTILAGE
OSSEOUS CALLUS
FORMATION
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TEXTBOOK OF ESSENTIAL PATHOLOGY BY HARSHMOHAN, 4TH EDITION
HEALING OF ORAL WOUNDS
Oral wounds heal faster and with less scarring than extra oral wounds.
It is mainly due to:
• Saliva
• Bacteria
• Phenotype of cells
FACTOR MECHANISM
Saliva
Moisture,ionic strength,ions-Mg
and Ca
growth factors( EGF,VEGF,TGFB
etc}
Bacteria
Stimulation of macrophage influx,
Direct stimulative action on
keratinocyte and fibroblast.
Phenotype of cells
Fetal like fibroblasts with unique
response, specialized epithelium
and Connective Tissue
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HEALING FOLLOWING SCALING &
ROOT PLANING
• 2 hours:
• Numerous
polymorphonuclear
leucocytes can be
seen b/w residual
epithelial cells &
crevicular surface.
• Dilation of blood
vessels, oedema &
necrosis in the
lateral wall of the
pocket
• 24 hrs: widespread
infiltration of
inflammatory cells
and migration of
keratinocytes have
been observed, in
all areas of the
remaining
epithelium
• 2 days: Entire
pocket is
epithelialized
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NEWMAN, TAKEI,KLOKKEVOLD,CARRANZA. 10TH EDITION.
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
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NEWMAN, TAKEI,KLOKKEVOLD,CARRANZA. 10TH EDITION.
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.
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
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42
within 2 weeks they connect with gingiva vessels
After 5-14 days surface epitheliazation is complete
During first 4 weeks keratinization is less than it was before surgery
1 month Complete epithelial repair
7 weeks Complete repair of the C.T.
Flow of GCF is initially increased after gingivectomy and diminishes as
healing progresses.
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NEWMAN, TAKEI,KLOKKEVOLD,CARRANZA. 10TH EDITION.
HEALING FOLLOWING FLAP SURGERY
Clot formation
1-3 days, migration of epithelial cells
by 1 week, epithelial attachment by means of hemidesmosomes
granulation tissue replaces clot
by 2nd week, collagen fibres appear & arranged parallel to root surface
by end of 1 month, well formed epithelial attachment
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LINDHE’S CLINICAL PERIODONTOLOGY 7TH ED.
SOCKET HEALING WITH GRAFT MATERIAL
PEDRO DE SOUSA GOMES ET AL CONCLUDED THAT:
Graft materials act as solid scaffolds which assist on coagulum stabilization during
the early phases of healing, by impeding the interference of destabilizing factors on
the clot maturation process.
Some graft materials may have a direct modulatory effect on the cellular behaviour,
leading to an increased production of extracellular matrix and its subsequent
maturation.
Socket grafting seems to be effective on allowing for the formation of mature bone,
further promoting ridge preservation by limiting the physiologic reduction, as
compared to ungrafted healing.
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Journal of oral and maxillofacial research 2019 July-sep
HEALING FOLLOWING GINGIVAL DEPIGMENTATION
The initial response
formation of protective
surface clot
Within 2 weeks,
capillaries connect with
gingival vessels
Capillaries derived from
blood vessels of PDL,
migrate into the GT
The underlying tissues
become acutely
inflamed,with some
necrosis.
Clot is then replaced by
granulation tissue.
Complete epithelial
repair takes about
1 month.
After 5-14 days surface
epithelization is
generally complete.
Vascularity returns to
normal in about 2-3
weeks.
Vascularity increases
thn begins to decrease
gradually as healing
takes place.
45 / 69
NEWMAN, TAKEI,KLOKKEVOLD,CARRANZA. 10TH EDITION.
STEM CELLS FOR REGENERATION
• Dental Stem cells can be isolated from dental tissues like
periodontal ligament, pulp of human exfoliated teeth or dental
follicle.
• Dental stem cells could be feasible tools for dental tissue
engineering.
• Stem cells are defined as ‘clonogenic cells capable of both self
renewal and multi-lineage’.
 IN GENERAL ,THREE CATEGORIES CAN BE
IDENTIFIED:-
• Embryonic stem cells(pluripotent)
• Adult stem cells(multipotent)
• Reprogrammed stem cells(either pluripotent or multipotent)
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STEM CELLS OF DENTAL TISSUE ORIGIN
• SHED: STEM CELLS FROM EXFOLIATED
DECIDUOUS TEETH
• DFSC: DENTAL FOLLICLE STEM CELLS
• DPSC: DENTAL PULP STEM CELLS
• PDSC: PERIODONTAL LIGAMENT STEM CELLS
• APICAL PAPILLA STEM CELLS
• EMBRYONIC STEM CELLS
47 / 69
STEM CELLS FOR PERIODONTAL REGENERATION
• Procedures to achieve periodontal regeneration have included root surface
conditioning, bone graft placement and growth factor application.
• One approach to periodontal regeneration involves incorporation of
progenitor cells in periodontal defect.
• Periodontal ligament stem cells have been shown to give rise to adherent
clonogenic clusters resembling fibroblasts that may develop into adipocytes,
osteoblast like cells and cementoblast like cells in vitro.
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49 / 69
STEM CELLS IN REGENERATIVE ENDODONTICS
• UNSPECIALIZED CELLS.
• CAN DIVIDE THROUGH MITOSIS
• DIFFERENTIATE INTO SPECIALIZED CELL TYPES
• SELF RENEW TO PRODUCE MORE STEM CELLS
ENDODONTIC IMPLICATIONS
ENDODONTIC IMPLICATIONS
ENDODONTIC IMPLICATIONS
• THE REACTION OF THE PERIRADICULAR TISSUES TO NOXIOUS
PRODUCTS OF TISSUE NECROSIS, BACTERIAL PRODUCTS AND
ANTIGENIC AGENTS FROM THE ROOT CANAL HAS BEEN DESCRIBED BY
FISH.
• FOUR WELL-DEFINED ZONES OF REACTION GIVEN BY FISH-
ZONE OF INFECTION
ZONE OF
CONTAMINATION
ZONE OF IRRITATION
ZONE OF
STIMULATION
50 / 69
COHEN’S , 11TH EDITION
WOUND HEALING AFTER
ENDODONTIC SURGERY
• THE INTIAL REPAIR THAT FOLLOWS A PERIRADICULAR
SURGICAL PROCEDURE OCCURS ACROSS THE MARGINS OF THE
LINE OF INCISION.
• THIS HEALING BY 1ST INTENTION USUALLY OCCUR WITHIN 5
DAYS, PROVIDED THE SUTURE REMAIN INTACT.
• IF THE SUTURES TEAR OR FAIL, THEN HEALING OCCUR BY
FORMATION OF GRANULATION TISSUE ( 2ND INTENTION) WHICH
LASTS FOR 4-6 WEEKS.
• REPAIR OF PERIRADICULAR TISSUES IS USUALLY COMPLETED
WITHIN A YEAR, AND A PROGRESSIVE REPAIR SHOULD BE
NOTICEABLE ON A RADIOGRAPH 6 MONTHS AFTER THE
OPERATION.
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COHEN’S , 11TH EDITION
DENTAL IMPLANTS AND HEALING
Soroush Irandoust & Sinan MĂźftĂź Concluded That:
Long-term bone healing/adaptation after a dental implant treatment starts with diffusion of
mesenchymal stem cells to the wounded region and their subsequent differentiation.
The healing phase is followed by the bone-remodeling phase.
The first and most important healing phase, osteoconduction, relies on the recruitment and
migration of osteogenic cells to the implant surface, through the residue of the peri-implant
blood clot.
The most important aspects of osteoconduction are the knock-on effects generated at the
implant surface, by the initiation of platelet activation, which result in directed osteogenic
cell migration.
There is de novo bone formation, which results in a mineralized interfacial matrix
equivalent to that seen in the cement line in natural bone tissue.
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EUROPEAN CELLS AND MATERIALS , VOL. 38, 2019
PLATELET RICH FIBRIN (PRF) IN
TISSUE HEALING AND
REGENERATION
JOHAN HARTSHORNE AND HOWARD GLUCKMAN
CONCLUDED THAT:
PRF IS INCREASINGLY BEING INVESTIGATED AND USED BY CLINICIANS
WORLDWIDE AS AN ADJUNCTIVE AUTOLOGOUS BIOMATERIAL TO PROMOTE
BONE AND SOFT TISSUE HEALING AND REGENERATION. IT IS DERIVED FROM
PATIENT’S OWN BLOOD, EASY TO MAKE AT CHAIRSIDE, EASY TO USE WITH
DAILY CLINICAL ROUTINE, WIDELY APPLICABLE WITH NO RISK OF REJECTION,
WHILST BEING FINANCIALLY REALISTIC FOR THE PATIENT.
53 / 69
FURTHER:
THE GOLD STANDARD FOR IN-VIVO TISSUE HEALING AND REGENERATION REQUIRES THE
MUTUAL INTERACTION BETWEEN A SCAFFOLD (FIBRIN MATRIX), PLATELETS, GROWTH
FACTORS, LEUKOCYTES, AND STEM CELLS. THESE KEY ELEMENTS ARE ALL ACTIVE
COMPONENTS OF PRF AND WHEN COMBINED AND PREPARED PROPERLY ARE INVOLVED IN
KEY PROCESSES OF TISSUE HEALING AND REGENERATION , WHILST AT THE SAME TIME
REDUCING ADVERSE EVENTS.
IT IS USED IN IMPLANTOLOGY, PERIODONTOLOGY, ORAL AND MAXILLOFACIAL SURGERY,
AND LATELY IN REGENERATIVE ENDODONTICS TO PROMOTE WOUND HEALING AMD
REGENERATION.
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ENDODONTIC REGENERATION : MATTHIAS WIDBILLER ET AL
HEALING OF SINUS TRACT
• SINUS IS A TRACT LEADING FROM AN ENCLOSED AREA
OF INFLAMMATION TO AN EPITHELIAL SURFACE, AND IS
ONE OF THE SEQUELAE OF INFLAMMATORY DISEASE.
• A SINUS TRACT IS A DRAINAGE DUCT FOR THE
SUPPURATION PRODUCED BY ABSCESSES.
• SUPPURATION FROM THE PERIAPICAL INFLAMMATORY
PROCESS MAY BE RESORBED BY THE HOST ORGANISM,
OR ELSE IT WILL FLOW THROUGH THE LESS RESISTANT
TISSUE AREA.
55 / 69
DAS. CONCISE TEXTBOOK OF SURGERY, 3RD EDITION
TREATMENT OF SINUS TRACT
• TREATMENT IS DIRECTED TOWARDS ELIMINATION OF THE SOURCE OF
INFECTION.
• OFFENDING TOOTH IS REMOVED IF IT IS TOO BADLY DECAYED, OR IF THERE
IS EXTENSIVE LOSS OF THE SURROUNDING ALVEOLAR BONE.
• IN MOST CASES, THE SINUS TRACT HEALS SPONTANEOUSLY IF THE INFECTED
PULP IS REMOVED, AND THE ROOT CANAL DEBRIDED AND FILLED.
56 / 69
DAS. CONCISE TEXTBOOK OF SURGERY, 3RD EDITION
HEALING AFTER EXTRACTION OF
TOOTH
57 / 69
DAS. CONCISE TEXTBOOK OF SURGERY, 3RD EDITION
HEALING OF RESIDUALALVEOLAR RIDGES
- RESIDUAL RIDGE IS THE TERM USED TO DESCRIBE THE
SHAPE OF THE CLINICAL ALVEOLAR RIDGE AFTER
HEALING OF THE BONE AND SOFT TISSUES AFTER
TOOTH EXTRACTION.
- AFTER TOOTH EXTRACTION, A CASCADE OF
INFLAMMATORY REACTIONS IS IMMEDIATELY
ACTIVATED, AND EXTRACTION SOCKET IS
TEMPORARILY CLOSED BY THE BLOOD CLOT.
- THERE IS PROLIFERATION AND MIGRATION OF
EPITHELIAL TISSUE WITHIN FIRST WEEK AND
DISRUPTED TISSUE INTEGRITY IS QUICKLY RESTORED.
- THE MOST STRIKING FEATURE OF THE EXTRACTION
WOUND HEALING IS THAT EVEN AFTER HEALING OF
THE WOUNDS, THE RESIDUAL ALVEOLAR RIDGE BONE
UNDERGOES A LIFE LONG CATABOLIC REMODELLING.
58 / 69
DEEPAK NALLASWAMY VEERAIYAN, 2ND EDITION
HEALING OF REIMPLANTED TOOTH
Clot
Fibroblast Proliferation
Reconnection
Reattachment of epithelium by 7th day
Complete regeneration of pdl within
2-4 weeks
59 / 69
NEWMAN, TAKEI,KLOKKEVOLD,CARRANZA. 10TH EDITION.
REMODELLING OF BONE IN ORTHODONTIC TOOTH
MOVEMENT
- BONE REMODELLING IS A COUPLED PROCESS IN
WHICH THERE IS LOCALIZED REMOVAL OF OLD
BONE (RESORPTION) AND REPLACEMENT WITH
NEWELY FORMED BONE.
-THE MAJOR REASON FOR REMODELLING IS TO
ENABLE THE BONE TO RESPOND, AND ADAPT TO
MECHANICAL STRESSES AS SEEN DURING
MECHANICAL LOADING DURING ORTHODONTIC
TOOTH MOVEMENT, AND IN ROOT RESORPTION.
- IN PRESSURE SIDE, OSTEOCLASTS RELEASE H
IONS TO DISSOLVE THE INORGANIC MATRIX AND
ENZYMES SUCH AS MMPs AND CATHEPSINS
RESORB ORGANIC MATRIX IN BONE.
- IN THE TENSION SIDE, OSTEOBLASTS FORMS NEW
BONE BY PRODUCING NEW ECM AND THEN
MINERALIZING IT.
60 / 69
INTERNATIONAL JOURNAL OF ORAL SCIENCE, (2021)13:20 BY YUAN LI ET AL
HEALING IN PATIENTS ON CHEMOTHERAPY/ RADIATION THERAPY
- THERE IS IMPAIRED HEALING RESPONSE.
-PULP MAY BECOME NECROTIC DURING RADIATION THERAPY.
-SYMPTOMATIC NONVITAL TEETH SHOULD BE ENDODONTICALLY
TREATED 1 WEEK BEFORE INITIATING RADIATION OR
CHEMOTHERAPY WHEREAS ASYMPTOMATIC NONVITAL TEETH MAY
BE DELAYED.
-DUE TO THE RISK OF OSTEORADIONECROSIS, ALL INVASIVE
SURGICAL PROCEDURES SHOULD BE AVOIDED FOR ATLEAST 6
MONTHS AFTER RADIATION THERAPY.
61 / 69
INGLE’S ENDODONTICS, 6TH EDITION
RECENT TRENDS IN MANAGEMENT OF WOUNDS
62 / 69
• Biopolymers, polymers that produced by living microorganisms are commonly
used as wound management.
• The used materials in wound dressings involve films, sponges, fibers or
hydrogels from natural and synthetic polymers and their combinations
63 / 69
Wound dressings from naturally-occurred polymers:
Naturally-occurring polymers are generally chosen for wound management over
synthetic polymers because they are economical, non-toxic to human body and
environmental-friendly. Polysaccharides are natural polymers which are frequently
applied as wound dressing materials. Cellulose, chitosan, pullulan, starch and β-
glucan, as well as collagen, hyaluronic acid and alginate are among the most used
polymers as wound dressings.
Chitosan (CS) is a well studied natural polymer, frequently used in biomedical
applications because of its antimicrobial activity and healing stimulation. It also
promotes drainage, prevents the buildup of exudates, and serves as auto-grafting bed
in wound therapy.
SUMMARY
The process by which healing occurs in a tissue is dependent on several factors:
-TYPE OF CELL, EXTENT OF INJURY ETC.
Depending on the type of wounds, healing process follows two pathways:
-HEALING BY PRIMARY INTENTION
-HEALING BY SECONDARY INTENTION
There are systemic and local factors which may delay wound healing (e.g. vitamin
deficiency, systemic conditions such as diabetes, cardiovascular diseases, drugs such as
nsaids, bisphosphonates etc.)
Complications of wound healing includes keloid formation, implantation cyst formation,
infection etc.
Factors which promotes healing includes good blood supply, nutrition, age , site of
wound etc.
64 / 69
CONCLUSION
UNDERSTANDING OF WOUND HEALING IS AS IMPORTANT AS
KNOWING THE PATHOGENESIS OF DISEASE, BECAUSE
SATISFACTORY WOUND HEALING IS THE ULTIMATE GOAL OF
TREATMENT.
IF WE ARE ABLE TO UNDERSTAND THE MECHANISM OF
PERIAPICAL WOUND HEALING, WE CAN DESIGN TREATMENT
APPROACHES THAT CAN MAXIMIZE FAVOURABLE CONDITIONS
FOR WOUND HEALING TO OCCUR.
65 / 69
• TEXTBOOK OF ESSENTIAL PATHOLOGY BY
HARSHMOHAN, 4TH EDITION
• ROBBINS AND COTRAN, PATHOLOGIC BASIS OF
DISEASE, 7TH EDITION
• BOYD’S TEXTBOOK OF PATHOLOGY 9TH EDITION
• DAS. CONCISE TEXTBOOK OF SURGERY, 3RD
EDITION
• LINDHE’S CLINICAL PERIODONTOLOGY 7TH
EDITION
• JOURNAL OF BURNS AND WOUNDS
(http://www.ncbi.nlm.nih.gov/pmc/journals/211/)
REFERENCES
66 / 69
67 / 69
• DEEPAK NALLASWAMY VEERAIYAN, 2ND EDITION
• ASIAN JOURNAL OF PHARMACEUTICAL SCIENCES 2020
• PHILLIPS’ SCIENCE OF DENTAL MATERIALS, 12TH
EDITION
• NEWMAN, TAKEI,KLOKKEVOLD,CARRANZA. 10TH
EDITION.
• BAU JOURNAL- HEALTH AND WELLBEING , ARTICLE 7,
VOLUME 2, ISSUE 1
• SRB’ S MANUAL OF SURGERY, 4TH EDITION
• Basic Considerations of wound Healing.Periodontology 2000 vol
19
68
69

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wound HEALINGG AND REPAIR PPT.pptx

  • 1. THE ABILITY TO HEAL IS INBUILT IN OUR PHYSIOLOGY. WE ONLY HELP BODY TO HEAL ITSELF AND REMOVE ANY OBSTACLES IN THE PATH OF HEALING. 1 / 69
  • 2. Wound Healing and Repair PRESENTED BY :- ADITI CHANDEL MDS 1ST YEAR DEPARTMENT OF PERIODONTOLOGY AND ORAL IMPLANTOLOGY 2/69 GUIDED BY : DR. BALJEET SINGH (PROFESSOR) DEPARTMENT OF PERIODONTOLOGY AND ORAL IMPLANTOLOGY
  • 3. CONTENTS • DEFINITION OF HEALING • TYPES OF HEALING • PHASES OF WOUND HEALING • FACTORS INFLUENCING WOUND HEALING • COMPLICATIONS OF WOUND HEALING • FRACTURE HEALING • PERIODONTOLOGY IMPLICATIONS • HEALING IN IMPLANTS • ENDODONTIC IMPLICATIONS • HEALING AFTER EXTRACTION OF TOOTH • HEALING OF REIMPLANTED TOOTH • REMODELLING OF BONE IN ORTHODONTICS • HEALING IN PATIENTS ON CHEMOTHERAPY/ RADIATION THERAPY • RECENT TRENDS IN MANAGEMENT OF WOUNDS • CONCLUSION • REFERENCES 3 / 69
  • 4. HEALING HEALING IS THE BODY RESPONSE TO INJURY IN AN ATTEMPT TO RESTORE NORMAL STRUCTURE AND FUNCTION. - WOUND HEALING IS A PRIMARY SURVIVAL MECHANISM AND IS A PROTECTIVE FUNCTION OF THE BODY THAT FOCUSES ON QUICK RECOVERY. -WONG ET AL, 2013 HEALING INVOLVES REGENERATION REPAIR 4 / 69
  • 5. 5 / 69 Robbins and cotran basic pathology 9th ed
  • 6. REGENERATION • WHEN HEALING TAKES PLACE BY PROLIFERATION OF PARENCHYMAL CELLS AND IT USUALLY RESULTS IN COMPLETE RESTORATION OF THE ORIGINAL TISSUES  PERIODONTAL REGENERATION is defined as the restoration of lost periodontium or supporting tissues and includes formation of new alveolar bone, new cementum and new periodontal ligament. Wang HL et al in 2005 THE FACTORS WHICH CONTROL HEALING AND REPAIR ARE COMPLEX AND THEY INCLUDE THE PRODUCTION OF VARIETY OF GROWTH FACTORS: EPIDERMAL GROWTH FACTORS FIBROBLAST GROWTH FACTORS ENDOTHELIAL GROWTH FACTOR PLATELET DERIVED GROWTH FACTOR TRANSFORMING GROWTH FACTOR- B 6 / 69 ESSENTIAL PATHOLOGY BY HARSHMOHAN, 4TH EDITION
  • 7. TISSUE PROLIFERATION ACTIVITY LABILE CELLS STABLE CELLS PERMANENT CELLS • CONTINUE TO MULTIPLY THROUGHOUT LIFE UNDER NORMAL PHYSIOLOGIC CONDITIONS. • E.G. SURFACE EPITHELIAL CELLS OF THE EPIDERMIS, HAEMOPOIETIC CELLS OF BONE MARROW ETC. • DECREASE OR LOSE THEIR ABILITY TO PROLIFERATE AFTER ADOLESCENCE. • CELLS FROM THESE TISSUE CAN UNDERGO RAPID DIVISION IN RESPONSE TO STIMULI. • E.G. PARENCHYMAL CELLS OF LIVER AND KIDNEY, BONE AND CARTILAGE CELLS, FIBROBLASTS ETC. • CANNOT UNDERGO MITOTIC DIVISION IN THE POSTNATAL LIFE. • E.G. NEURONS AND CARDIAC MUSCLE CELLS. 7 / 69 ESSENTIAL PATHOLOGY BY HARSHMOHAN, 4TH EDITION
  • 9. REPAIR WHEN HEALING TAKES PLACE BY PROLIFERATION OF CONNECTIVE TISSUE ELEMENTS RESULTING IN FIBROSIS AND SCARRING. REPAIR IS THE REPLACEMENT OF INJURED TISSUES BY THE FIBROUS TISSUE. GRANULATIO -N TISSUE FORMATION CONTRACTI- -ON OF WOUNDS 9 / 69 ROBBINS AND COTRAN, PATHOLOGIC BASIS OF DISEASE, 7TH ED.
  • 11.  Granulation Tissue formation • GRANULATION TISSUE IS THE HALLMARK OF HEALING. • GRANULATION TISSUE PROGRESSIVELY INVADES THE SITE OF INJURY • THE TERM GRANULATION TISSUE DERIVES ITS NAME FROM ITS PINK, SOFT, GRANULAR APPEARANCE OF TISSUE. PHASE OF INFLAMMATION PHASE OF CLEARANCE PHASE OF INGROWTH OF GRANULATION TISSUE 11 / 69 ROBBINS AND COTRAN, PATHOLOGIC BASIS OF DISEASE, 7TH ED.
  • 12. 1: INFLAMMATION: BLOOD CLOTS, EXUDATION OF PLASMA, NEUTROPHILS, MONOCYTES WITHIN 24 HOURS. 2: CLEARANCE: PROTEOLYTIC ENZYMES LIBERATED FROM NEUTROHILS, AUTOLYTIC ENZYMES FROM DEAD TISSUE CELLS, PHAGOCYTIC ACTIVITY OF MACROPHAGES. 3: INGROWTH OF GRANULATION TISSUE: ANGIOGENESIS FIBROGENESIS 12 / 69 ROBBINS AND COTRAN, PATHOLOGIC BASIS OF DISEASE, 7TH ED.
  • 13. -FORMATION OF NEW BLOOD VESSELS AT THE SITE OF INJURY BY PROLIFERATION OF ENDOTHELIAL CELLS FROM MARGINS OF SEVERED BLOOD VESSELS. -THE PROCESS OF ANGIOGENESIS IS STIMULATED WITH PROTEOLYTIC DESTRUCTION OF BASEMENT MEMBRANE. -VARIOUS FACTORS INFLUENCING ANGIOGENESIS: VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF), PLATELET DERIVED GROWTH FACTOR, TRANSFORMING GROWTH FACTOR-B, BASIC FIBROBLAST GROWTH FACTOR (bFGF). 13 / 69 ANGIOGENESIS ROBBINS AND COTRAN, PATHOLOGIC BASIS OF DISEASE, 7TH ED.
  • 15. IN THE NEWLY FORMED BLOOD VESSELS, FIBROBLASTS ORIGINATE FROM FIBROCYTES AS WELL AS THE MITOTIC DIVISION OF FIBROBLASTS. A COLLAGEN FIBRILS BEGIN TO APPEAR BY 6TH DAY. B AS MATURATION PROCEEDS, MORE COLLAGEN IS FORMED WHERE AS THE NUMBER OF FIBROBLASTS DECREASES. C THERE IS FORMATION OF INACTIVE LOOKING SCAR KNOWN AS CICATRISATION D 15 / 69 FIBROGENESIS ROBBINS AND COTRAN, PATHOLOGIC BASIS OF DISEASE, 7TH ED.
  • 16.  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. MECHANISM OF WOUND CONTRACTION CONTRACTION OF COLLAGEN DEHYDRATION MYOFIBROBLASTS 16 / 69 DAS. CONCISE TEXTBOOK OF SURGERY, 3RD EDITION
  • 17. WOUND HEALING A WOUND IS A BREAK IN THE INTEGRITY OF THE SKIN OR TISSUES OFTEN WHICH MAY BE ASSOCIATED WITH DISRUPTION OF THE STRUCTURE AND FUNCTION. ( SRB 4TH EDITION) A WOUND IS A CUT OR BREAK IN THE CONTINUITY OF ANY TISSUE, CAUSED BY INJURY OR OPERATION. ( BAILLIERE’S 23RD EDITION ) 17 /69 JOURNAL OF BURNS AND WOUNDS (http://www.ncbi.nlm.nih.gov/pmc/journals/211/)
  • 18. 18 / 69 ROBBINS AND COTRAN, PATHOLOGIC BASIS OF DISEASE, 7TH ED.
  • 19. Growth Factors and Cytokines Affecting Various Steps in Wound Healing Monocyte chemotaxis PDGF, FGF, TGF-ß Fibroblast migration PDGF, EGF, FGF, TGF-ß, TNF, IL-1 Fibroblast proliferation PDGF, EGF, FGF, TNF Angiogenesis VEGF, Ang, FGF Collagen synthesis TGF-ß, PDGF Collagenase secretion PDGF, EGF, FGF, TNF, TGF-ß inhibits PDGF- platelet-derived growth factor FGF- fibroblast growth factor TGF- transforming growth factor EGF- epidermal growth factor IL- interleukin TNF- tumor necrosis factor VEGF- vascular endothelial growth factor 19 / 69 ROBBINS AND COTRAN, PATHOLOGIC BASIS OF DISEASE, 7TH ED.
  • 21. TYPES OF WOUND HEALING WOUND HEALING CAN BE ACCOMPLISHED IN ONE OF THE FOLLOWING WAYS: • HEALING BY FIRST INTENTION (PRIMARY UNION) • HEALING BY SECOND INTENTION (SECONDARY UNION) • HEALING BY TERTIARY INTENTION 21 / 69 ESSENTIAL PATHOLOGY BY HARSHMOHAN, 4TH EDITION
  • 22. Healing by First Intention (Primary Union) • CLEAN INCISED WOUND OR SURGICAL UNINFECTED WOUND. • MORE EPITHELIAL REGENERATION THAN FIBROSIS. • WOUND HEALS RAPIDLY WITH COMPLETE CLOSURE WITHOUT MUCH LOSS OF CELLS AND TISSUE. 22 / 69 ESSENTIAL PATHOLOGY BY HARSHMOHAN, 4TH EDITION
  • 23. EVENTS IN PRIMARY UNION • OCCURS WITHIN 24 HOURS. • APPEARANCE OF POLYMORPHS, WHICH ARE REPLACED BY MACROPHAGES ON 3rd DAY. INITIAL HAEMORRHAGE ACUTE INFLAMMATORY RESPONSE EPITHELIAL CHANGES ORGANISATION SUTURE TRACKS • BLOOD CLOTS IN THE SPACE BETWEEN APPROXIMATED INCISED WOUND SURFACES. • IT SEALS THE WOUND AGAINST DEHYDRATION AND INFECTION. •PROLIFERATION AND MIGRATION OF BASAL CELLS OF EPIDERMIS AS EPITHELIAL SPURS. •SCAB FORMATION SEPERATING UNDERLYING VIABLE DERMIS FROM OVERLYING NECROTIC MATERIAL AND CLOT. •BY 5TH DAY MULTILAYERED NEW EPIDERMIS IS FORMED •BY 3RD DAY FIBROBLAST INVADE WOUND AREA . •BY 5TH DAY NEW COLLAGEN FIBRILS IS FORMED. •IN 4 WEEKS SCAR TISSUE WITH SCANTY CELLULAR AND VASCULAR ELEMENTS. •FILLING SPACE WITH HAEMORRHAGE, INFLAMMATORY CELL REACTION, FORMATION OF YOUNG COLLAGEN. •STITCH ABSCESS, IMPLANTATION OR EPIDERMAL CYSTS. 23 / 69 BOYD’S TEXTBOOK OF PATHOLOGY 9TH EDITION
  • 24. Suture Classification 24/69 Suture materials can be described in three ways, according to their structure, source and fate within the body:- •Structure – Monofilament/Braided/Barbed • Source – Natural or Synthetic • Fate – Absorbable or Non-absorbable
  • 25. HEALING BY SECOND INTENTION (SECONDARY UNION) • OPEN WOUND WITH LARGE TISSUE DEFECT, AT TIMES INFECTED. • EXTENSIVE LOSS OF CELLS AND TISSUES. • WOUND IS NOT APPROXIMATED BY SURGICAL SUTURES BUT IS LEFT OPEN. 25 / 69 ESSENTIAL PATHOLOGY BY HARSHMOHAN, 4TH EDITION
  • 26. EVENTS IN SECONDARY UNION INITIAL HAEMORRHAGE INFLAMMATION EPITHELIAL CHANGES GRANULATION TISSUE WOUND CONTRACTION 26 /69 BOYD’S TEXTBOOK OF PATHOLOGY 9TH EDITION
  • 27. HEALING BY TERTIARY INTENTION 27/69 Tertiary wound healing, or healing by delayed primary closure, occurs when there is a need to delay the wound-closing process. This occurs when the process of secondary intention is intentionally interrupted and the wound is mechanically closed. This usually occurs after granulation tissue has formed.
  • 28. FEATURES PRIMARY SECONDARY CLEANLINESS CLEAN NOT CLEAN INFECTION NOT INFECTED INFECTED MARGINS SURGICALLY CLEAN IRREGULAR SUTURES USED NOT USED HEALING SMALL GRANULATION TISSUE LARGE GRANULATION TISSUE OUT COME LINEAR SCAR IRREGULAR WOUND COMPLICATION NOT FREQUENT FREQUENT 28/ 69 DAS. CONCISE TEXTBOOK OF SURGERY, 3RD EDITION
  • 29. EXTRACELLULAR MATRIX : WOUND STRENGTH • THE ECM IS A STRUCTURAL SUPPORT NETWORK MADE UP OF DIVERSE PROTEINS, SUGARS AND OTHER COMPONENTS. • IT INFLUENCES WIDE NUMBER OF CELLULAR PROCESSES INCLUDING MIGRATION, WOUND HEALING AND DIFFERENTIATION. • ECM COMPRISES OF: (1) FIBROUS STRUCTURAL PROTEIN – COLLAGENS AND ELASTIN (2) ADHESIVE GLYCOPROTEIN (3) PROTEOGLYCANS AND HYALURONIC ACID • THESE MACROMOLECULES ARE PRESENT IN INTERCELLULAR JUNCTIONS AND CELL SURFACES AND FORM TWO GENERAL ORGANIZATIONS:  INTERSTITIAL MATRIX  BASEMENT MEMBRANE 29 / 69 ESSENTIAL PATHOLOGY BY HARSHMOHAN, 4TH EDITION
  • 30.  COLLAGEN: - TYPE I: FOUND IN SKIN, BONE, AND MATURE SCARS. - TYPE II: CARTILAGE. - TYPE III: ABUNDANT IN EMBRYONIC AND PLIABLE TISSUES. FIRST COLLAGEN DEPOSITED IN WOUND HEALING. - TYPE IV: BASEMENT MEMBRANES AND ASSOCIATED WITH LAMININ AND OTHER MATRIX COMPONENTS. 30 / 69 ROBBINS AND COTRAN, PATHOLOGIC BASIS OF DISEASE, 7TH ED.
  • 31.  COLLAGEN PROVIDES TENSILE STRENGTH, WHEREAS ELASTIC FIBERS PROVIDE RECOIL, AND THUS TEND TO BE FOUND IN THE AORTA, SMALLER ARTERIES, SKIN, LUNG, AND UTERUS. ELASTIC FIBERS 31 / 69 ESSENTIAL PATHOLOGY BY HARSHMOHAN, 4TH EDITION
  • 32. STRUCTURAL GLYCOPROTEIN • FIBRONECTIN: (NECTERE, TO BIND) • BINDS TO COLLAGENS, PROTEOGLYCANS, FIBRINOGEN, FIBRIN, CELL SURFACES, BACTERIA AND DNA. • ONE OF THE FIRST STRUCTURAL MOLECULES DEPOSITED DURING EMBRYONIC DEVELOPMENT. • FOUND IN TISSUE AND PLASMA. • SYNTHESIZED BY HEPATOCYTES. 32 / 69 ESSENTIAL PATHOLOGY BY HARSHMOHAN, 4TH EDITION
  • 33. • PROTEOGLYCANS: • USED TO BE CALLED MUCOPOLYSACCHARIDES, BUT ARE NOW REFFERED TO AS GLYCOSAMINOGLYCANS. • HIGHLY HYDROPHILIC, AND FORM HYDRATED GELS, EVEN AT LOW CONCENTRATION. • SEEN IN EARLY WOUND HEALING 33 / 69 ESSENTIAL PATHOLOGY BY HARSHMOHAN, 4TH EDITION
  • 34. FACTORS INFLUENCING HEALING SYSTEMIC LOCAL NUTRITION :- e.g. Protein and Vit.C deficiency inhibit collagen Synthesis and Retard Healing . Infection- cause delay in wound healing. Circulatory Status:- inadequate blood supply caused by arteriosclerosis or venous abnormalities also impair healing. Mechanical factors:- such as early motion of wounds cause delay in healing. Hormones:- such as glucocorticoids will inhibit collagen synthesis. Foreign bodies:- ununecessary sutures or fragments of steel, glass or even bone can impede healing. Systemic Conditions Retarding Healing: AIDS/HIVinfection,Menopause, Connective Tissue Disorder such as EHLER DANLOS SYNDROME, CVS Disease etc Size, location and type of wound:- wound in richly vascularized areas heals faster , small wounds produced intentionally heals faster than larger ones caused by trauma 34 / 69 ROBBINS AND COTRAN, PATHOLOGIC BASIS OF DISEASE, 7TH ED.
  • 35. SYSTEMIC MEDICATION AFFECTING WOUND HEALING - BISPHOSPHONATES: E.g. Etidronate, Alendronate, Pamidronate - GLUCOCORTICOIDS: E.g. Prednisone, Beclomethasone - NSAIDS: E.g. Diclofenac, Naproxen, Ibuprofen - CYCLO OXYGENASE - 2 INHIBITORS: E.g. Celecoxib, Rofecoxib 35 / 69 TEXTBOOK OF ESSENTIAL PATHOLOGY BY HARSHMOHAN, 4TH EDITION
  • 36. COMPLICATIONS OF WOUND HEALING • INFECTION • IMPLANTATION CYST (EPIDERMAL) • PIGMENTATION • DEFICIENT SCAR FORMATION • INCISIONAL HERNIA • HYPERTROPHIED SCARS AND KELOID FORMATION • EXCESSIVE CONTRACTION • NEOPLASIA 36 / 69 COHEN’S , 11TH EDITION
  • 37. FRACTURE HEALING • PRIMARY UNION OF FRACTURE • SECONDARY UNION OF FRACTURE HEMATOMA INGROWTH OF GRANULATION TISSUE REMODELLING CALLUS COMPOSED OF WOVEN BONE AND CARTILAGE OSSEOUS CALLUS FORMATION 37 / 69 TEXTBOOK OF ESSENTIAL PATHOLOGY BY HARSHMOHAN, 4TH EDITION
  • 38. HEALING OF ORAL WOUNDS Oral wounds heal faster and with less scarring than extra oral wounds. It is mainly due to: • Saliva • Bacteria • Phenotype of cells FACTOR MECHANISM Saliva Moisture,ionic strength,ions-Mg and Ca growth factors( EGF,VEGF,TGFB etc} Bacteria Stimulation of macrophage influx, Direct stimulative action on keratinocyte and fibroblast. Phenotype of cells Fetal like fibroblasts with unique response, specialized epithelium and Connective Tissue 38 / 69
  • 39. HEALING FOLLOWING SCALING & ROOT PLANING • 2 hours: • Numerous polymorphonuclear leucocytes can be seen b/w residual epithelial cells & crevicular surface. • Dilation of blood vessels, oedema & necrosis in the lateral wall of the pocket • 24 hrs: widespread infiltration of inflammatory cells and migration of keratinocytes have been observed, in all areas of the remaining epithelium • 2 days: Entire pocket is epithelialized 39 / 69 NEWMAN, TAKEI,KLOKKEVOLD,CARRANZA. 10TH EDITION.
  • 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 40 / 69 NEWMAN, TAKEI,KLOKKEVOLD,CARRANZA. 10TH EDITION.
  • 41. 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. 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 41/ 69
  • 42. 42 within 2 weeks they connect with gingiva vessels After 5-14 days surface epitheliazation is complete During first 4 weeks keratinization is less than it was before surgery 1 month Complete epithelial repair 7 weeks Complete repair of the C.T. Flow of GCF is initially increased after gingivectomy and diminishes as healing progresses. 42/ 69 NEWMAN, TAKEI,KLOKKEVOLD,CARRANZA. 10TH EDITION.
  • 43. HEALING FOLLOWING FLAP SURGERY Clot formation 1-3 days, migration of epithelial cells by 1 week, epithelial attachment by means of hemidesmosomes granulation tissue replaces clot by 2nd week, collagen fibres appear & arranged parallel to root surface by end of 1 month, well formed epithelial attachment 43 / 69 LINDHE’S CLINICAL PERIODONTOLOGY 7TH ED.
  • 44. SOCKET HEALING WITH GRAFT MATERIAL PEDRO DE SOUSA GOMES ET AL CONCLUDED THAT: Graft materials act as solid scaffolds which assist on coagulum stabilization during the early phases of healing, by impeding the interference of destabilizing factors on the clot maturation process. Some graft materials may have a direct modulatory effect on the cellular behaviour, leading to an increased production of extracellular matrix and its subsequent maturation. Socket grafting seems to be effective on allowing for the formation of mature bone, further promoting ridge preservation by limiting the physiologic reduction, as compared to ungrafted healing. 44 / 69 Journal of oral and maxillofacial research 2019 July-sep
  • 45. HEALING FOLLOWING GINGIVAL DEPIGMENTATION The initial response formation of protective surface clot Within 2 weeks, capillaries connect with gingival vessels Capillaries derived from blood vessels of PDL, migrate into the GT The underlying tissues become acutely inflamed,with some necrosis. Clot is then replaced by granulation tissue. Complete epithelial repair takes about 1 month. After 5-14 days surface epithelization is generally complete. Vascularity returns to normal in about 2-3 weeks. Vascularity increases thn begins to decrease gradually as healing takes place. 45 / 69 NEWMAN, TAKEI,KLOKKEVOLD,CARRANZA. 10TH EDITION.
  • 46. STEM CELLS FOR REGENERATION • Dental Stem cells can be isolated from dental tissues like periodontal ligament, pulp of human exfoliated teeth or dental follicle. • Dental stem cells could be feasible tools for dental tissue engineering. • Stem cells are defined as ‘clonogenic cells capable of both self renewal and multi-lineage’.  IN GENERAL ,THREE CATEGORIES CAN BE IDENTIFIED:- • Embryonic stem cells(pluripotent) • Adult stem cells(multipotent) • Reprogrammed stem cells(either pluripotent or multipotent) 46 / 69
  • 47. STEM CELLS OF DENTAL TISSUE ORIGIN • SHED: STEM CELLS FROM EXFOLIATED DECIDUOUS TEETH • DFSC: DENTAL FOLLICLE STEM CELLS • DPSC: DENTAL PULP STEM CELLS • PDSC: PERIODONTAL LIGAMENT STEM CELLS • APICAL PAPILLA STEM CELLS • EMBRYONIC STEM CELLS 47 / 69
  • 48. STEM CELLS FOR PERIODONTAL REGENERATION • Procedures to achieve periodontal regeneration have included root surface conditioning, bone graft placement and growth factor application. • One approach to periodontal regeneration involves incorporation of progenitor cells in periodontal defect. • Periodontal ligament stem cells have been shown to give rise to adherent clonogenic clusters resembling fibroblasts that may develop into adipocytes, osteoblast like cells and cementoblast like cells in vitro. 48 / 69
  • 49. 49 / 69 STEM CELLS IN REGENERATIVE ENDODONTICS • UNSPECIALIZED CELLS. • CAN DIVIDE THROUGH MITOSIS • DIFFERENTIATE INTO SPECIALIZED CELL TYPES • SELF RENEW TO PRODUCE MORE STEM CELLS
  • 50. ENDODONTIC IMPLICATIONS ENDODONTIC IMPLICATIONS ENDODONTIC IMPLICATIONS • THE REACTION OF THE PERIRADICULAR TISSUES TO NOXIOUS PRODUCTS OF TISSUE NECROSIS, BACTERIAL PRODUCTS AND ANTIGENIC AGENTS FROM THE ROOT CANAL HAS BEEN DESCRIBED BY FISH. • FOUR WELL-DEFINED ZONES OF REACTION GIVEN BY FISH- ZONE OF INFECTION ZONE OF CONTAMINATION ZONE OF IRRITATION ZONE OF STIMULATION 50 / 69 COHEN’S , 11TH EDITION
  • 51. WOUND HEALING AFTER ENDODONTIC SURGERY • THE INTIAL REPAIR THAT FOLLOWS A PERIRADICULAR SURGICAL PROCEDURE OCCURS ACROSS THE MARGINS OF THE LINE OF INCISION. • THIS HEALING BY 1ST INTENTION USUALLY OCCUR WITHIN 5 DAYS, PROVIDED THE SUTURE REMAIN INTACT. • IF THE SUTURES TEAR OR FAIL, THEN HEALING OCCUR BY FORMATION OF GRANULATION TISSUE ( 2ND INTENTION) WHICH LASTS FOR 4-6 WEEKS. • REPAIR OF PERIRADICULAR TISSUES IS USUALLY COMPLETED WITHIN A YEAR, AND A PROGRESSIVE REPAIR SHOULD BE NOTICEABLE ON A RADIOGRAPH 6 MONTHS AFTER THE OPERATION. 51 / 69 COHEN’S , 11TH EDITION
  • 52. DENTAL IMPLANTS AND HEALING Soroush Irandoust & Sinan MĂźftĂź Concluded That: Long-term bone healing/adaptation after a dental implant treatment starts with diffusion of mesenchymal stem cells to the wounded region and their subsequent differentiation. The healing phase is followed by the bone-remodeling phase. The first and most important healing phase, osteoconduction, relies on the recruitment and migration of osteogenic cells to the implant surface, through the residue of the peri-implant blood clot. The most important aspects of osteoconduction are the knock-on effects generated at the implant surface, by the initiation of platelet activation, which result in directed osteogenic cell migration. There is de novo bone formation, which results in a mineralized interfacial matrix equivalent to that seen in the cement line in natural bone tissue. 52 / 69 EUROPEAN CELLS AND MATERIALS , VOL. 38, 2019
  • 53. PLATELET RICH FIBRIN (PRF) IN TISSUE HEALING AND REGENERATION JOHAN HARTSHORNE AND HOWARD GLUCKMAN CONCLUDED THAT: PRF IS INCREASINGLY BEING INVESTIGATED AND USED BY CLINICIANS WORLDWIDE AS AN ADJUNCTIVE AUTOLOGOUS BIOMATERIAL TO PROMOTE BONE AND SOFT TISSUE HEALING AND REGENERATION. IT IS DERIVED FROM PATIENT’S OWN BLOOD, EASY TO MAKE AT CHAIRSIDE, EASY TO USE WITH DAILY CLINICAL ROUTINE, WIDELY APPLICABLE WITH NO RISK OF REJECTION, WHILST BEING FINANCIALLY REALISTIC FOR THE PATIENT. 53 / 69
  • 54. FURTHER: THE GOLD STANDARD FOR IN-VIVO TISSUE HEALING AND REGENERATION REQUIRES THE MUTUAL INTERACTION BETWEEN A SCAFFOLD (FIBRIN MATRIX), PLATELETS, GROWTH FACTORS, LEUKOCYTES, AND STEM CELLS. THESE KEY ELEMENTS ARE ALL ACTIVE COMPONENTS OF PRF AND WHEN COMBINED AND PREPARED PROPERLY ARE INVOLVED IN KEY PROCESSES OF TISSUE HEALING AND REGENERATION , WHILST AT THE SAME TIME REDUCING ADVERSE EVENTS. IT IS USED IN IMPLANTOLOGY, PERIODONTOLOGY, ORAL AND MAXILLOFACIAL SURGERY, AND LATELY IN REGENERATIVE ENDODONTICS TO PROMOTE WOUND HEALING AMD REGENERATION. 54 / 69 ENDODONTIC REGENERATION : MATTHIAS WIDBILLER ET AL
  • 55. HEALING OF SINUS TRACT • SINUS IS A TRACT LEADING FROM AN ENCLOSED AREA OF INFLAMMATION TO AN EPITHELIAL SURFACE, AND IS ONE OF THE SEQUELAE OF INFLAMMATORY DISEASE. • A SINUS TRACT IS A DRAINAGE DUCT FOR THE SUPPURATION PRODUCED BY ABSCESSES. • SUPPURATION FROM THE PERIAPICAL INFLAMMATORY PROCESS MAY BE RESORBED BY THE HOST ORGANISM, OR ELSE IT WILL FLOW THROUGH THE LESS RESISTANT TISSUE AREA. 55 / 69 DAS. CONCISE TEXTBOOK OF SURGERY, 3RD EDITION
  • 56. TREATMENT OF SINUS TRACT • TREATMENT IS DIRECTED TOWARDS ELIMINATION OF THE SOURCE OF INFECTION. • OFFENDING TOOTH IS REMOVED IF IT IS TOO BADLY DECAYED, OR IF THERE IS EXTENSIVE LOSS OF THE SURROUNDING ALVEOLAR BONE. • IN MOST CASES, THE SINUS TRACT HEALS SPONTANEOUSLY IF THE INFECTED PULP IS REMOVED, AND THE ROOT CANAL DEBRIDED AND FILLED. 56 / 69 DAS. CONCISE TEXTBOOK OF SURGERY, 3RD EDITION
  • 57. HEALING AFTER EXTRACTION OF TOOTH 57 / 69 DAS. CONCISE TEXTBOOK OF SURGERY, 3RD EDITION
  • 58. HEALING OF RESIDUALALVEOLAR RIDGES - RESIDUAL RIDGE IS THE TERM USED TO DESCRIBE THE SHAPE OF THE CLINICAL ALVEOLAR RIDGE AFTER HEALING OF THE BONE AND SOFT TISSUES AFTER TOOTH EXTRACTION. - AFTER TOOTH EXTRACTION, A CASCADE OF INFLAMMATORY REACTIONS IS IMMEDIATELY ACTIVATED, AND EXTRACTION SOCKET IS TEMPORARILY CLOSED BY THE BLOOD CLOT. - THERE IS PROLIFERATION AND MIGRATION OF EPITHELIAL TISSUE WITHIN FIRST WEEK AND DISRUPTED TISSUE INTEGRITY IS QUICKLY RESTORED. - THE MOST STRIKING FEATURE OF THE EXTRACTION WOUND HEALING IS THAT EVEN AFTER HEALING OF THE WOUNDS, THE RESIDUAL ALVEOLAR RIDGE BONE UNDERGOES A LIFE LONG CATABOLIC REMODELLING. 58 / 69 DEEPAK NALLASWAMY VEERAIYAN, 2ND EDITION
  • 59. HEALING OF REIMPLANTED TOOTH Clot Fibroblast Proliferation Reconnection Reattachment of epithelium by 7th day Complete regeneration of pdl within 2-4 weeks 59 / 69 NEWMAN, TAKEI,KLOKKEVOLD,CARRANZA. 10TH EDITION.
  • 60. REMODELLING OF BONE IN ORTHODONTIC TOOTH MOVEMENT - BONE REMODELLING IS A COUPLED PROCESS IN WHICH THERE IS LOCALIZED REMOVAL OF OLD BONE (RESORPTION) AND REPLACEMENT WITH NEWELY FORMED BONE. -THE MAJOR REASON FOR REMODELLING IS TO ENABLE THE BONE TO RESPOND, AND ADAPT TO MECHANICAL STRESSES AS SEEN DURING MECHANICAL LOADING DURING ORTHODONTIC TOOTH MOVEMENT, AND IN ROOT RESORPTION. - IN PRESSURE SIDE, OSTEOCLASTS RELEASE H IONS TO DISSOLVE THE INORGANIC MATRIX AND ENZYMES SUCH AS MMPs AND CATHEPSINS RESORB ORGANIC MATRIX IN BONE. - IN THE TENSION SIDE, OSTEOBLASTS FORMS NEW BONE BY PRODUCING NEW ECM AND THEN MINERALIZING IT. 60 / 69 INTERNATIONAL JOURNAL OF ORAL SCIENCE, (2021)13:20 BY YUAN LI ET AL
  • 61. HEALING IN PATIENTS ON CHEMOTHERAPY/ RADIATION THERAPY - THERE IS IMPAIRED HEALING RESPONSE. -PULP MAY BECOME NECROTIC DURING RADIATION THERAPY. -SYMPTOMATIC NONVITAL TEETH SHOULD BE ENDODONTICALLY TREATED 1 WEEK BEFORE INITIATING RADIATION OR CHEMOTHERAPY WHEREAS ASYMPTOMATIC NONVITAL TEETH MAY BE DELAYED. -DUE TO THE RISK OF OSTEORADIONECROSIS, ALL INVASIVE SURGICAL PROCEDURES SHOULD BE AVOIDED FOR ATLEAST 6 MONTHS AFTER RADIATION THERAPY. 61 / 69 INGLE’S ENDODONTICS, 6TH EDITION
  • 62. RECENT TRENDS IN MANAGEMENT OF WOUNDS 62 / 69 • Biopolymers, polymers that produced by living microorganisms are commonly used as wound management. • The used materials in wound dressings involve films, sponges, fibers or hydrogels from natural and synthetic polymers and their combinations
  • 63. 63 / 69 Wound dressings from naturally-occurred polymers: Naturally-occurring polymers are generally chosen for wound management over synthetic polymers because they are economical, non-toxic to human body and environmental-friendly. Polysaccharides are natural polymers which are frequently applied as wound dressing materials. Cellulose, chitosan, pullulan, starch and β- glucan, as well as collagen, hyaluronic acid and alginate are among the most used polymers as wound dressings. Chitosan (CS) is a well studied natural polymer, frequently used in biomedical applications because of its antimicrobial activity and healing stimulation. It also promotes drainage, prevents the buildup of exudates, and serves as auto-grafting bed in wound therapy.
  • 64. SUMMARY The process by which healing occurs in a tissue is dependent on several factors: -TYPE OF CELL, EXTENT OF INJURY ETC. Depending on the type of wounds, healing process follows two pathways: -HEALING BY PRIMARY INTENTION -HEALING BY SECONDARY INTENTION There are systemic and local factors which may delay wound healing (e.g. vitamin deficiency, systemic conditions such as diabetes, cardiovascular diseases, drugs such as nsaids, bisphosphonates etc.) Complications of wound healing includes keloid formation, implantation cyst formation, infection etc. Factors which promotes healing includes good blood supply, nutrition, age , site of wound etc. 64 / 69
  • 65. CONCLUSION UNDERSTANDING OF WOUND HEALING IS AS IMPORTANT AS KNOWING THE PATHOGENESIS OF DISEASE, BECAUSE SATISFACTORY WOUND HEALING IS THE ULTIMATE GOAL OF TREATMENT. IF WE ARE ABLE TO UNDERSTAND THE MECHANISM OF PERIAPICAL WOUND HEALING, WE CAN DESIGN TREATMENT APPROACHES THAT CAN MAXIMIZE FAVOURABLE CONDITIONS FOR WOUND HEALING TO OCCUR. 65 / 69
  • 66. • TEXTBOOK OF ESSENTIAL PATHOLOGY BY HARSHMOHAN, 4TH EDITION • ROBBINS AND COTRAN, PATHOLOGIC BASIS OF DISEASE, 7TH EDITION • BOYD’S TEXTBOOK OF PATHOLOGY 9TH EDITION • DAS. CONCISE TEXTBOOK OF SURGERY, 3RD EDITION • LINDHE’S CLINICAL PERIODONTOLOGY 7TH EDITION • JOURNAL OF BURNS AND WOUNDS (http://www.ncbi.nlm.nih.gov/pmc/journals/211/) REFERENCES 66 / 69
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