- Periapical wound healing is the host's programmed immunoinflammatory defense mechanism in response to infection or injury. It involves complex overlapping stages including inflammation, proliferation, and remodeling. - The primary difference between healing after surgery and nonsurgical root canal treatment is that surgery requires blood clot formation and may result in faster healing dynamics. After successful nonsurgical root canal treatment, periapical inflammatory tissues will be eliminated mainly by phagocytic debridement. - Healing involves osseous healing of trabecular and cortical bone as well as dentoalveolar healing resulting in repair or regeneration of the apical attachment apparatus. Various factors like age, tooth position, and root canal filling material can

1. PERIAPICAL WOUND HEALING

2. • Wound healing is the response of living tissuesto any injury which causes disruptionof the continuity and/or function
of those tissuesand involves a complex seriesof biologicalevents,some occurring simultaneouslyand others
dependent upon the completion of prior events.
• Wound healing is basically dependent upon the type of tissue wounded and the type of wound that the tissue receives
The tissueswounded in periradicular surgery are the mucoperiostealtissues(gingiva,alveolar mucosa, palatal
mucosa, and underlying periosteum), periradicular tissues(bone, gingival ligament, and periodontalligament), and
radicular tissues(cementum and dentin).
• These tissues,with the exception of dentin, are collectively termed the periodontium and form the supporting
structuresof the teeth. The tissuesof the periodontium receive three types of surgicalwounding during periradicular
surgery: incisionalwounding, blunt dissectionalwounding, and excisionalwounding. Incisionalwounds are made
with a scalpel,outline the perimeter of the flap, and involve the mucoperiosteal tissues.
• Blunt dissectional wounds are made with a periostealelevator, separating mucoperiosteal tissuesfrom cortical bone
during the flap reflection procedure.Excisional wounds are made with a rotary instrument in removing bone and
resectingthe root end . Thus, with multiple types of oral tissuesreceiving various types of surgical wounding, the
entire wound healing response to periradicular surgery is understandably diverse and complicated.

3. • Connective tissue involves a processof repair via the formation of granulation tissue,whereas non-connective
tissue,such as that of the glandular organs, smooth muscles,skeletalmuscles and peripheralnerves, involves the
proliferation,and therefore, regeneration,of the remaining tissue18.These two processes are dependent upon the
regenerativecapacityof the affected cells,the extent of the affectedsite, and the proliferativeactivity of the
stromal tissue.
• Regenerationinvolves a process of tissue renewal with cells that have similar characteristicsto those that were
previously lost; it is the morphological and functionalrestorationof tissue.Conversely, repair is characterized by
the formation of connectivetissue at the site of the lesion,
• During pulp infection, the occluded blood supply of the root canal becomes conducive to bacterial periapicalregion
is elicitedto neutralizethe antigen.immune cells,which are then organized into a barrier to sequester the infection.
• Bone resorptionand bone formation are processesinvolving the activity of osteoclasts,osteoblasts,and osteocytes;
they are affected by the systemic and local conditions66.However, bone homeostasisis disrupted during apical
periodontitis,which promotes increasedrates of bone resorption

5. • Wound healing is the host’s programmed immunoinflammatory defense mechanism in response to
infection or injury
• The primary difference is that healing after surgery requires a blood clot formation. Surgical excision may
result in a faster healing process compared to NSRCT, which exhibits slower healing dynamics. After
successful NSRCT, periapical inflammatory tissues will be eliminated, mainly by phagocytic debridement.
• The basic phases of wound healing can be divided into three overlapping stages: inflammation,
proliferation, and remodeling. Within these three broad phases a complex and coordinated series of events
occur that include chemotaxis and phagocytosis during the inflammatory phase.
• Neocollagenesis, epithelialization, and angiogenesis result in the formation of granulation tissue during the
proliferation phase. During the final remodeling phase, there is active collagen remodeling and tissue
maturation that culminates in either repair or regeneration

6. • Healing after Apical Microsurgery
• (1) osseous healing involving trabecularand cortical bone and (2)
dentoalveolar healing that results in repair or regenerationof apical
attachment apparatus(alveolar bone, periodontalligament, and
cementum)
• After apical surgery, the resected cavity is occupied by a
coagulum, which is slowly replaced by granulationtissue
originating from the periodontalligament and endosteum. The
formation of new bone begins in the internal area and progresses
externally toward the level of the former cortical plate.
As newly laid woven bone reaches the lamina propria, the overlying
membrane becomesfunctional periodontium (osseous healing)
(Figure 13.3).
Progenitor cellsfrom the periodontal ligament differentiateinto
periodontal ligament cells and cementoblasts to cover the resected
root surface and lead to regenerationof the cementum and the
periodontal ligament (dentoalveolar healing

7. • Incomplete Healing/Scar Formation Scar tissue formation after apical surgery has been extensively
studied. It was demonstrated that 26% of defects radiographically larger than 10 mm resulted in scar
formation after apical surgery.
• Furthermore, when the bony defect perforated both cortical plates (“through-and-through lesion”), the
incidence of scar tissue formation may reach 60%. However, there is a lack of clinical evidence to indicate
that large or through-and-through lesions will always result in scar tissue formation, even when no barrier
membrane is used after apical surgery

8. • Radiographically,scar formation has been characterizedby a typical sunburst appearance due to bone trabeculae radiating
from a center of the lesion that may remain radiolucent indefinitely(Figure 13.4). To this day the mechanisms of scar
formation are not fully understood.
• Nevertheless,during incomplete healing,the healing is periosteal in nature and progressesfrom the outside of the lesion
towards the inside,resulting in a residualdefect and accumulation of nonfunctionalfibrous tissue.

9. • In this context, the study conductedby Kerekes and Tronstad (1979) should also be mentioned, as the authors reported an 85%
success rate with complete healingand 6% still undergoinghealingin the treatmentof teeth with apical periodontitis,without
using calcium hydroxide. The healingprocess is known to be quickerand the recovery completein young people compared to
older people.
• Similar studies to the present one indicatedthat age is an important factorin the healingof periapical lesions in patients aged
between 11 and 24 years (Gesi et al 2006).
• It is assumed that periapical lesions occur due to the immune response to antigens from the root canal. Theirinteractionwith
antibodiescauses immunological reactionsin periapical tissues. Immunological reactionsinvolve the removal of invasive
antigenic substances. The healingof periapical structures dependson their abilityto develop an immune responseto the action
of variousantigens. The presence of immunocompetentcells, especiallyT cells, in periapicallesions indicatesthe presence of
humoral immune responses in that area. These complex immune responses play an importantrole in periapicallesions.
However, immune functions are weakened when reaching sexual maturity due to changesin the number and proliferationof
immunocompetent cells.
• The decreasein T-cell proliferation in response to antigens, togetherwith the poor reaction ofmature T cells to antigens,are
the main factorsassociatedwith lower immune responses associated with increasedage (Matsuo et al 1994, Kurashima &
Utsuyama 1997).

10. • In contrast, in a study that includedpatientsaged between 19 and 86 years, Peters and Wesselink (2002) reported that there isno
connectionbetween patient age and periapicalhealing. In their study, they obtaineda 71% success rate of root canal therapy
performed in two sessions, after a period of 4½ years. Theseobservationsare consistentwith studies showing no significant
difference in periapical tissue response when T cell functionshave been suppressed (Peters & Wesselink 2002), similar to elderly
patients.
• According to this conclusion, we can say that immunodeficiencyis not a significant factor in the healing ofperiapicallesions in the
elderly.Due to the controversy overthe influence of age on periodontal healing,there is a need for more comparative studies.
Khabbaz and Papadopoulos (1999) have determinedthat periapical woundhealingis not affectedby the presenceof root canal filling
material in the periapical tissue.
• They also concludedthat healingis due to infectioncontrol during root canal preparation and, equally, during root canal filling.
Katebzadehet al (2000) also mentionthe importance of root canal fillingin the healingof apical periodontitis.
• Failure due to overfillingis actuallycaused by infecteddentin and debris pushed beyond the apex during instrumentation. Augsberger and Peters (1990) stressed
that periapicalwould healing takes place even if the root canal sealer reaches the periapicaltissue, and possible failureis due to other factors,such as improper
handling.
• Lin et al. (1992) stressedthat root canal fillingmaterialhas a much lower irritanteffect than microbialfactors.
• Huang et al (2002) have concluded that the biocompatibilityof the root canal sealer is extremelyimportantas it stimulates the reorganizationof the affected
periapicaltissuethat it comes into contact with.
• Tanomaru et al (1998) stated that in case of teeth with chronic periapical infection,root canal fillingmaterialswith antibacterial propertiesthat do not irritatethe
periapicalor periradicular tissues can stimulateapexification

11. • Leonardo et al (2003) showed that periapical tissue reaction is excellent in the presence of AH Plus. In
their study, they observed the presence of mineralized tissue apposition in the apical zone of the root and,
in many cases, soft tissue mineralization processes around the apex.
• Azar et al (2000) have found that freshly mixed AH Plus has mutagenic and cytotoxic properties, which
disappear when filling is completed. Dartar et al (2003) reported the lack of AH Plus cytotoxicity in vitro
and the promotion of bone healing. Other studies have shown that the type and amount of root canal filling
material used, its resorption capability and especially its toxicity are all important factors in the healing of
periapical lesions.
• Another interesting aspect of periapical healing is the link between the healing process and the position of
the tooth in the dental arch.

12. • It seems that maxillary second premolars as well as maxillary and mandibular canines have a better
prognosis than other teeth. The first maxillary molars often have two middle-vestibular root canals, and
one of them could remain unspotted, untreated and unfilled, thus maintaining the infection active.
• Maxillary lateral incisors present anatomical variations, such as pronounced curvature in the apical area
and very thin roots, aggravating the correct mechanicaland antiseptic treatment as well as the root canal
filling process. However, other studies suggest that there is no connection between periapical healing and
tooth position in the dental arch (Orstavik & Horsted-Bindslev 1993)

13. Healing Evaluation Using CBCT
• it illustratesthe defectsin cancellousbone and corticalbone separately, making it a more sensitive tool to identifyapical
periodontitis. Furthermore, image reconstruction occurs in a multiplanar reformation mode, which allows the highlightingof
specific anatomicregions and structures around the resectedroot surface, such as periodontal ligament space, lamina dura,
and cortical plate.
• Moreover, it allows for differentiation betweenvarious bone densities. The aforementioned anatomicstructuresare centralto
current criteriaused to assess apical surgery healing onCBCT. For example, complete healingis attributed to those cases
where the periodontal ligament space and the lamina dura have completelyreformed over the resected rootsurfaces
• Other interestinghealingpatternsobserved on CBCT include completehealingin the immediate vicinityof the resectedroot
surface, along with a complete cortical bone repair in width and density; however,the trabecular bone adjacent to the
resected rootis of low density
• These cases can be attributed to limitedhealing,which is considered a successful outcome. This differentiationbetween
various bone densitiesis unique to CBCT. It has been hypothesized that reduced radiolucent areas representeither scar tissue,
immature bone, or bone-liketissue without adequate mineralization, which at this particular stage of healingwould not be
radiopaque enoughto be detectedby CBCT. Another interestingobservationconcernstooth positionin the bony architecture.

15. Ingrida Dapkute et al PeriapicalWound Healing Microsurgery in Endodontics, First Edition.
Syngcuk Kim and Samuel Kratchman. © 2018 John Wiley & Sons, Inc. Published 2018 by John

16. • The healingof periapical structures dependson their ability to develop an immune response to the actionof variousantigens.
The presence of immunocompetent cells, especiallyT cells, in periapical lesions indicates the presence of humoral immune
responses in that area. These complex immune responses play an important role in periapical lesions. However, immune
functions are weakened when reachingsexual maturity due to changes in the number and proliferation ofimmunocompetent
cells. The decrease in T-cell proliferationin response to antigens, togetherwith the poor reactionof mature T cells to
antigens, are the main factorsassociatedwith lower immune responses associatedwith increasedage (Matsuo et al 1994,
Kurashima & Utsuyama 1997).
• Due to the controversyover the influence ofage on periodontal healing, there is a need for more comparative studies.
Khabbaz and Papadopoulos (1999) have determinedthat periapical woundhealingis not affectedby the presenceof root
canal filling material in the periapicaltissue. They also concludedthat healingis due to infectioncontrol during root canal
preparationand, equally, during root canal filling. Katebzadeh et al (2000)also mention the importanceof root canal filling
in the healingof apical periodontitis. Failure due to overfillingis actually causedby infecteddentin and debris pushed
beyond the apex during instrumentation.

17. • Augsberger and Peters (1990) stressed that periapical would healing takes place even if the root canal
sealer reaches the periapical tissue, and possible failure is due to other factors, such as improper handling.
• Lin et al. (1992) stressed that root canal filling material has a much lower irritant effect than microbial
factors.
• Huang et al (2002) have concluded that the biocompatibility of the root canal sealer is extremely important
as it stimulates the reorganization of the affected periapical tissue that it comes into contact with.
• Tanomaru et al (1998) stated that in case of teeth with chronic periapical infection, root canal filling
materials with antibacterial properties that do not irritate the periapical or periradicular tissues can
stimulate apexification

18. • and healing. Leonardo et al (2003)showed that periapical tissue reactionis excellentin the presenceof AH Plus. In their
study, they observed the presence of mineralizedtissue apposition in the apical zoneof the root and, in many cases, soft
tissue mineralizationprocessesaround the apex. Azar et al (2000) have found that freshly mixed AH Plus has mutagenicand
cytotoxicproperties, which disappearwhen filling is completed.
• Dartar et al (2003) reported the lack of AH Plus cytotoxicity in vitro and the promotion of bone healing. Other studies have
shown that the type and amount of root canal filling material used, its resorptioncapabilityand especially itstoxicityare all
important factorsin the healingof periapical lesions.
• Another interestingaspect of periapicalhealingis the link between the healing process and the position of the tooth in the
dental arch. It seems that maxillarysecond premolars as well as maxillaryand mandibularcanineshave a betterprognosis
than other teeth. The first maxillarymolars often have two middle-vestibular root canals,and one of them could remain
unspotted, untreatedand unfilled, thus maintainingthe infectionactive.
• Maxillarylateral incisorspresent anatomical variations, such as pronouncedcurvaturein the apical area and verythin roots,
aggravatingthe correct mechanicaland antiseptic treatmentas well as the root canal fillingprocess. However, other studies
suggest that there is no connectionbetween periapicalhealing and tooth positionin the dental arch (Orstavik & Horsted-
Bindslev 1993)

19. • At the end of 12-month period, only 20 patients presented
themselves for check-up. Therefore, only 22 teeth could be
assessed, 11 treated with AH Plus (group A) and 11 with
RealSeal SE (group B). Data regarding clinical signs and
symptoms related were collected and recorded, compared with
baseline values, but they were not subjected to statistical analysis.

21. PRINCIPLE OF PERIAPICAL WOUND HEALING
• It is a host’s ‘‘programmed event,’’which begins with
(1) hemostasisor coagulation phase
(2) inflammationphase
(3) proliferative phase
(4) regenerationand/or repairphase
(5) remodeling ormaturation phase
Regardless of the size of a wound, granulationtissue in the proliferative phase, a necessaryelement of wound healing, fills the
wound and helps complete thewound healing process

22. Wound healing usually involves recruitment and differentiation of progenitor/stem cells into tissue
committed cells .
Wound healing can result in either regeneration or repair, depending on the nature of wound, availability of
progenitor/stem cells, growth/differentiation factors, and microenvironmental cues such as adhesion
molecules, extracellular matrix (ECM), and associated noncollagenous protein molecules
Regeneration represents the replacement of damaged tissue by the cells of the same tissue. Importantly, it
reconstitutes, although not completely, both the architecture and functions of the original tissue, such as
healing of an uninfected simple surgical incision of the skin approximated by surgical sutures, because tissue
destruction and granulation tissue formation are minimum

23. • Regenerationof periapicaltissuesafter periapicalsurgery requires
(1) recruitment of progenitor/stem cells to differentiateinto committed osteoblasts,PDL cells, and cementoblasts
(2) growth/differentiationfactors as necessarysignalsfor attachment,migration, proliferation, and differentiationof
progenitor/stem cells;
(3) local microenvironmental cues such as adhesionmolecules,and ECM and associated noncollagenousprotein
molecules

24. • Cementoblasts, PDL cells, and osteoblasts in the periapical tissues are differentiated cells, they still retain
the potential to undergo cell division and proliferation on stimulation by appropriate signals during
physiologic turnover and periapical wound healing
• In small periapical lesions, resident osteoblasts, PDL cells, and cementoblasts might be capable of
restoring damaged periapical tissues. However, in large periapical lesions, periapical wound healing
requires recruitment and differentiation of progenitor cells/stem cells into osteoblasts, cementoblasts, and
PDL cells.
• It has been also shown that PDL harbors adult stem cells in the paravascular spaces, and these stem cells
are capable of differentiating into PDL-like, cementoblastlike, and osteoblast-like cells . In addition, bone
marrow mesenchymal stem cells and periosteal osteoprogenitor cells are capable of differentiating into
osteoblasts

25. • Cell differentiation is regulated by extrinsic local microenvironmental cues and intrinsic master regulatory
genes . Cell differentiation is usually a part of the regenerative process .
• Regardless of the size of periapical lesions, persistence of root canal infection is the primary cause of
inflamed periapical tissues not to heal after endodontic therapy .
• There are no published studies demonstrating that membrane barriers and/or bone grafts contributed to the
cause of periapical surgery failure. Complete periapical wound healing after periapical surgery should
include regeneration of alveolar bone, PDL, and cementum

26. • In 1974, platelets regenerative potentiality was introduced, and Ross et al.,[3] were first to describe a
growth factor from platelets. After activation of the platelets which are trapped within fibrin matrix,
growth factors released and stimulate the mitogenic response in the bone periosteum during normal wound
healing for repair of the bone.[4] Better understanding of physiologic properties of platelets in wound
healing since last two decades led to increase its therapeutic applications in the various forms showing
varying results.

27. • Kim et al. 2012 May Animal study The PRF-mixed tricalcium phosphate (TCP) showed more rapid bone
healing than the (recombinant human bone morphogenic protein 2) rhBMP-2-coated TCP or the TCP-only
control
• Jankovic et al. 2012 Apr Randomized controlled clinical study Use of a PRF membrane in gingival
recession treatment provided acceptable clinical results, followed by enhanced wound healing and
decreased subjective patient discomfort compared to connective tissue graft (CTG)-treated gingival
recessions
• Rudagi et al. 2012 Apr Case report This case report presents the successful healing and apexification with
combined use of MTA as an apical barrier and autologous PRF membrane as an internal matrix

28. • Pradeep et al. 2012 Mar Randomized control clinical trial Porous hydroxyapatite(HA) when added to PRF
increasesthe regenerativeeffectsobserved with PRF in treatment of human three wall intrabony defects
• Anitua et al. 2012 Mar In vivo Practically, plasma rich in growth factors (PRGF) may present a role in reducing
tissue inflammation after surgery, increasing new bone formation, and promoting vascularization of bone tissue
• Peck et al. 2012 Mar Case report L-PRF is a newly developed plateletconcentratethat has successfully been used
in a number of surgical proceduresto optimize wound healing and was used to stimulatebone formation to
facilitateideal placement of implants
• Clipet et al. 2012 Feb In vitro PRF conditioned medium induced gene expression in osteoblasts.Expressionof
osteopontin and osteocalcinand late osteogenicmarkers was observed and confirmed PRF is useful in stimulating
tissue healing and bone regeneration
• Jayalakshmi et al. 2012 Case report Combined use of PRF and b-tricalcium phosphate(b-TCP) for bone
augmentation in treatment of periapicaldefectsis a potentialtreatment alternativefor faster healing than using
these biomaterialsalone

29. • Simonpieri et al. 2009 Jun In vivo PRF membranes are particularlyhelpful for periosteum healing and maturation.The thick peri-implantgingival is
as a result of several healing phases on a PRF membrane layer
• Simon et al. 2009 May Animal study PRFM alone may be the best graft for ridge preservationprocedures
• Simonpieri et al. [13] 2009 Apr In vivo PRF membranesprotects the surgical site,promotes soft tissuehealing,and when itsfragmentsmixed with
graft materialit functions as a “biologicalconnector”
• Magremanne et al. 2009 Apr Case report PRF may induce healing of non-reossifiedcystic cavity by supplying local growth factors
• Aroca et al. [19] 2009 Feb In vivo Modified coronally advanced flap (MCAF)is a predictable treatmentfor multipleadjacent Miller Class I or II
recession-typedefects. The addition of a PRF membrane positioned under the MCAFprovided inferiorroot coverage, but an additionalgain in
gingival/mucosalthickness (GTH)at 6 months compared to conventional therapy
• Anilkumaret al. [17] 2009 Jan Case report Describedlaterallydisplaced flap technique with PRF membrane technique as a navel root coverage
approach for gingival recessionof the mandibular anterior teeth
• Diss et al. [85] 2008 May In vivo The bone-added osteotome sinus floor elevation(BAOSFE)procedure with PRF as grafting materialcan lead to an
endosinus bone gain
• Lundquist et al. [86] 2008 May Review PRF provides sustainedrelease and protection against proteolyticdegradation of endogenous fibrogenic
factorsimportantfor wound healing

30. PLATELET RICH PLASMA
• PRP blood clot, on the other hand, contains 4% RBCs, 95% platelets,and 1% WBCs.
• The PRP preparationprotocol requires collectionof blood with anticoagulant,centrifugation in two steps, and induced
polymerizationof the plateletconcentrate using calcium chloride and bovine thrombin.
• PRP has been used in conjunctionwith different grafting materials in bone augmentation procedures since the day of its

31. PRF
• Choukroun developed the PRF in 2001 at France
• Actually the plateletsand leukocytecytokines are important part in role play of this biomaterial,but the fibrin matrix
supporting them is very helpful in constituting the determining elements responsiblefor real therapeuticpotential of
PRF.
• Cytokines are immediately used and destroyedin a healing wound. The harmony between cytokinesand their
supporting fibrin matrix has much more unique importance than any other constant.
• A fibrin glue, enriched with cytokines (such as PRP) with large uncontrollableand short-term effect is less better than
a physiologicfibrin matrix (such as PRF) with good and better effects.
Naik, et al.: Healing potential of PRF Journal of Conservative Dentistry | Jul-Aug 2013 | Vol 16 | Issue 4 289 to accumulate platelets and
released cytokines in a fibrin clot.

32. • Choukroun attemptedto evaluatethe potential of PRF in combinationwith freeze-dried boneallograft(FDBA) in sinus floor
elevation to enhance bone regeneration ,ninesinus floor augmentationswere performed.
• Out of nine; in six sites, FDBA with PRF (test group), and in three sites FDBA without PRF (control group) was used. After
4 months, the test group and for the control group after 8 months; bone specimensfrom the augmented region during the
implant insertion procedurewere harvested andevaluated.
• After 4 months of healing time, histologic maturationof the test group appearsto be identical to that of the control group
which was for a period of 8 months with equivalent quantities for both protocols.
• In various bone reconstruction procedures Choukroun’s PRF could provide a possible new bone.
• Mazor stated that use of PRF as the sole fillingmaterial during a simultaneous sinus lift and implantationprocedure had
stabilizeda good amount of regenerated bonein the subsinus cavityup to the tip of implants in a case series through a
radiologicaland histological evaluationat after 6 months from the surgery.
• Also they advocatedthat Choukroun’sPRF, which is a simple and inexpensivebiomaterial in systematic use during a sinus
lift seems as an acceptableoption.

33. • PRF membranes protects the surgical site; promotes soft tissue healing; and when its fragments mixes with graft
material, it functions as a “biologicalconnector” between the different elements of graft and acts as a matrix which
supports neoangiogenesis,capture of stem cells, and migration of osteoprogenitor cellsto the center of graft.
• PRF plugs can also be used in treating the residualextraction sockets.
• Use of autologous PRF in extractedsocket filling after immediate bone augmentationusing titanium membranes
applied to the socket walls and primary closure was found to be feasibleand safe with adequate bone filling after 8
weeks or above for implant fixation.
• Anilkumar reported PRF as a potentialnovel root coverage approach for treatinggingival recession in mandibular
anterior teeth using combined laterally positionedflap technique and PRF membrane.
• Combined use of PRF and bone graft with good resultshas also been reported for combined periodontic-
endodontic furcation defect.

34. • PRF as a scaffoldingmaterial in an infected necrotic immature tooth for pulpal regenerationand tooth
revitalization as it satisfiesmany criteria of an ideal physicalscaffold.
• Another advantage of using PRF as a scaffold is that it has a trimolecular or equilateral fibrin branch junction
which makes its architecture flexible and can support cytokine enmeshment and cellularmigration.
• 20 ml of 5.25% sodium hypochloritewas used to irrigate the canal. Care was taken to ensure that the irrigating
needle was loose in the canal and that the NaOCl irrigationwas performed very slowly.
• Triple antibioticpaste was used for disinfectionof the canal becausethis particularcombination is effective in
addressing the diverse flora present in the root canal.
• Sato et al, investigated this drug combination in vitro and found it to be very effective in the sterilization of carious
lesions, necrotic pulps, infected root dentin and periapicallesions. This drug combination is also effectivein killing
the bacteria in the deep layers of root canal dentin

35. • Directly over the PRF clot the MTA was packed and condensed to obtain a tight coronal seal as it is
hydrophilic and needs moisture to set, which is a favorable property when there is potential for moisture
contamination in the clinical setting, and also MTA by itself provides signaling molecules for the growth
of the stem cells.
• The positive response to cold test and EPT testing in our case report can be attributed to the placement of
MTA slightly below the level of CEJ.
• If we had got negative response to the vitality testing it could have been due to the thickness of MTA
which halts the growth of the new tissue ahead of it and also if placement of MTA is near CEJ elicits a
higher positive response.

36. • Bone grafting materials include autografts, allografts, xenografts, and alloplasts. They have been used in
periodontal regenerative therapy as space maintainers for selective denuded root surfaces or to act as
osteoinductive or osteoconductive biomaterials for regeneration of bone loss as a result of periodontal
disease .
• Bone grafts have also been successfully used to regenerate new bone formation in implant dentistry . The
same bone grafting materials, especially alloplasts such as calcium sulfate, have been widely used in
periapical surgery to enhance new bone formation as well.
• Calcium sulfate must dissolve in tissue fluid or integrate into bone before or during new bone formation.
Similar to periodontal regenerative therapy, evaluation of wound healing after periapical surgery by using
bone grafts should also include regeneration of PDL

37. • Most bone grafts, especially calcium sulfate used in periapical surgery, are neither osteogenic nor
osteoinductive Therefore, calcium sulfate is not capable of recruiting mesenchymal stem cells in the bone
marrow or endosteum and osteoprogenitor cells in the periosteum to differentiate into committed pre-
osteoblasts.
• Calcium sulfate is osteoconductive which refers to the ability of some foreign materials to serve as a
scaffold on which cells can attach, migrate, and grow and divide .
• Even though bone grafts are osteoconductive, they are not ideal materials for promoting periodontal tissue
regeneration such as PDL and cementum in periodontal regenerative therapy because they are not able to
stimulate the formation of a new connective tissue attachment.
• Many studies have clearly demonstrated that calcium sulfate can serve as scaffold for new bone formation
in periapical surgery.

38. • Biologically, a blood clot is a better space filleror ECM than all bone grafting materials.
• A blood clot is the host’s own biologic product and is essential to tissue wound healing. Without a blood clot, tissue wound
healing would be impaired as in a dry socket after tooth extraction.
• A blood clot is composed of insolublefibrin and many growth factors/cytokinessuch as platelet-derivedgrowth factor
(PDGF), TGF-b, vascular endothelialgrowth factor (VEGF), endothelial growthfactor, insulin-likegrowth factor (IGF), and
fibroblastgrowth factor (FGF) .
• During wound healing, fibrin filamentscross-linkedto fibronectin provide a provisional matrix for attachment and migration
of immune cells, fibroblasts,endothelial cells, and tissue cells . The degradedproducts of fibrin, by plasmin, are chemotactic
to the host’s immune cells .
• In addition, FGF, TGF-b, VEGF, and endothelial growth factor in blood clot promote angiogenesisto enhancetissue wound
healing .
• Bone grafts alone without a blood clot or angiogenic factors are unlikelyto be capable of promoting periapical wound
healing

39. CON
• PRF can be used to promote wound healing, bone regeneration, graft stabilization, wound sealing, and
hemostasis. Because the fibrin matrix is better organized, it is able to more efficiently direct stem cell
migration
• Release of growth factors from PRF through in vitro studies and good results from in vivo studies led to
optimize the clinical application of PRF. It was shown that there are better results of PRF over PRP.
• Dohan proved a slower release of growth factors from PRF than PRP and observed better healing
properties with PRF. It was observed and shown that the cells are able to migrate from fibrin scaffold;
while some authors demonstrated the PRF as a supportive matrix for bone morphogenetic protein a

40. • Growth factors/cytokinesplay a crucial role in tissue wound healing because they regulateimmune function and
proliferationand differentiationof cells participatingin wound healing . Growth factors are multifunctionaland
often have more than 1 target cell .
• Many of the host’s natural growth factors have been synthesizedin vitro and used alone or incorporatedinto bone
grafts in periapicalsurgery to enhance new bone formation. In a clinicalstudy, combination of platelet-richplasma
and tricalciumphosphate placed in a bony defect after periapicalsurgery was shown to enhance bone regeneration .
• However, when exogenous recombinant human bone morphogenetic protein-1 (rhOP-1) (95), rhBMP-2 (96), IGF
combined with PDGF, or FGF alone was deliveredto the bony defect during periapicalsurgery, the
growth/differentiationfactors did not demonstrateany obvious benefit to the process of bone healing.
• The concentrationand stability of exogenous growth factor/factorsand their presence in relation to the temporal
and spatialexpression of other growth/differentiationfactors as well as their exact target cells are important in
tissuewound healing

41. Factors Influencing Periapical Wound Healing
• Numerous factors such as infection, foreign bodies,systemic disease,and an impaired host’s immune system can
influence wound healing.Infection and foreign bodies are the most important factors that can affect periapical
wound healing.
• Implanted biomaterialssuch as bone grafts, despite being inert and nontoxic, often trigger adverse foreign body
reactionssuch as inflammation, fibrosis, infection,and thrombosis .
• The foreign body reaction composed of activatedmacrophages and foreign body giant cells is the end-stage
responseof inflammation and wound healing after implantationof biomaterials.Foreign bodies favor infection due
to biofilm formation .
• In addition, any foreign materialssuch as bone grafts have to dissolvein tissue fluid or be phagocytosedby
activated macrophages before wound healing can be completed. If that does not occur, bone grafts will be
surrounded by fibrous connectivetissue or embedded in newly formed bone, as in some instancesof periodontal
regenerativetherapy

42. 9-year-oldboy came with the chief complaint ofbroken upper front tooth (#8) along with discoloration.
Past dental history revealedtrauma to his upper front tooth (#8). The medical history of the patient was noncontributory. Intraoral
examinationof his teeth revealedthe presence ofdiscolored tooth #8along with Ellis class IV fracture.Tooth #8 was sensitive to both
percussion and periapical palpation tests. It did not respond to CO2 ice and electric pulp test (EPT). Periodontal probingdepth of the
tooth #8 was within normal limit.
IntraoralPeriapical Radiographicexamination of tooth #8 revealedan immature root and an open apex associatedwith periapical
radiolucency. Further radiographic examinationof the tooth revealeda 3 mm open apex along with thin dentinalwalls that appeared
prone to fracture. So a clinical decision of performing a regenerative endodontictreatmentusing Choukroun’s Platelet Rich Fibrin was
decided.

43. A written informed consent was obtained from the patient’s mother. Local anesthesia was achieved using
Lignocaine (1:100000 adrenaline.
After the rubber dam application, access cavity preparation was done on the tooth #8.
The canal was thoroughly irrigated with 20 ml of 5.25% sodium hypochlorite solution (Novo Dental Product,
India) and nuetralised with saline.
Following this, irrigation was done using 10ml of hexidine solution (0.2% Chlorhexidine, Vishal Dentocare,
India) and dried with paper points (Dentsply Maillefer Ballaigues).

44. • A mixture of Ciprofloxacin(Cifran 500mg, Ranbaxy Lab, India), Metronidazole(Metrogyl 400mg, J.B.Chemicals
and Pharmaceuticals,India), and Minocycline paste (Minoz 50 mg, Ranbaxy Lab, India) was prepared into a
creamy consistencyand introduced into the canal using a lentulospiral.
• A cotton pellet was placed and the cavity was temporarily sealed with cavit (Dental Productsof India, India). The
patient returned after 21 days to the clinic and was asymptomatic. Local anesthesiawas given, followed by rubber
dam isolation;then the accesscavity was reopened and thoroughly irrigated with sterilesaline solution and dried
with paper points.
• A 12ml sample of whole blood was drawn intravenously from the patient’s right antecubitalvein and centrifuged
(REMI Model R-8c with 12×15ml swing out head) under 3000 rpm for 10 minutes to obtain the PRF which was
jelly like in consistency.The PRF was condensed into the canal using a finger plugger (Dentsply Maillefer
Ballaigues)till the level the cementoenameljunction. Grey MTA (ProRoot MTA; Dentsply) was placed directly
over the PRF to a thicknessof 3mm followed by a wet cotton pellet and cavit.

45. • The patient was recalled after 3 days and the setting of MTA was confirmed. The access cavity was then double
sealed with GIC and Composite restoration . The patient returned to the clinic after 3 months, 6 months, 9 months
and 1 year for review and was asymptomatic; the tooth #8 showed negative response to percussion and palpation
tests and responded positive to CO2 ice or an electric pulp tester (EPT).
• Radiograph revealed continued thickening of the dentinal walls, root lengthening, regression of the periapical
lesion and apical closure

46. • Based on the clinicaland radiographic examinationwe can only say with certaintythat the pulp space had returnedto a vital
state. Based on research in avulsed teethand on a recent study on infectedteeth, it is more likely that the tissue in the pulp
space is more similar to periodontal ligamentthan to pulp tissue.
• The potential theory behind the success of the presentedcase could be attributedto a study conductedby Huang et al, who
concludedthat the PRF causes proliferationof human Dental Pulp Cells and increases the protein expressionof
osteoprotegerin (OPG) and alkalinephosphatase(ALP) activity.
• Some amounts of human dental pulp cells present in the apical papilla usuallyremain vital even in case of a large periapical
lesion. After the regression of the inflammation andunder the influenceof Hertwigs EpithelialRoot Sheath these Dental
Pulp Cells differentiateinto odontoblasts like cells.
• OPG and ALP expression are generally regardedas markers of odontoblastic differentiation.As there was no bleedingin the
root canal before placing the PRF we conclude that whatever tissue was produced in the canal could be attributedto the
presence ofPRF.
• On the basis of the results obtainedin our case report we conclude that revitalizationof necroticinfected immature tooth is
possible under conditionsof total canal disinfectionand PRF is an ideal biomaterial forpulp-dentin complexregeneration

47. • Periapical tssue reactions, such as inflammatory cell infiltration,bone resorption and epithelialproliferationin
apical periodontitisare the products of root canal infection.After surgicalendodontic therapy, periapicalwound
healing should follow exactly the same course as that of nonsurgicalendodontic therapy.
• The only difference is that surgicalendodontic therapy will heal faster than nonsurgicalendodontic therapy
because of more effectiveartificialdebridement of infectedor wounded periapicaltissuesby surgicalprocedures as
compared with biologicaldebridement by phagocytesin nonsurgicalprocedures .
• Grupe et al. suggested that the epithelialcells of apical cysts are capable of division and proliferation by virtue of
their ability to undertake anaerobic glycolysis.There is no evidence that epithelialcells in inflammatory apical
cysts behave like malignant neoplasticcells, which are encoded with oncogenes and can self divide in the absence
of appropriate extracellular signals, such as mitogens,cyclins,or cyclin-dependent protein kinases
• The remnants of epithelium left in the periapicaltissuesafter surgicalendodontic procedures will regress by
programmed cell death similar to that of nonsurgicalendodontic therapy if irritantshave been removed

49. METHODS FOR NONSURGICAL MANAGMENT OF
PERIAPICAL LESIONS
• Conservative root canal treatment without adjunctive therapy
• Bhaskar has suggested that instrumentation should be carried1 mm beyond the apical foramen when a periapicallesion is
evident ona radiograph.This may cause transitoryinflammation and ulcerationof the epitheliallining resulting in resolutionof
the cyst
• Bender in his commentaryon Bhaskar’s hypothesis has added that penetrationof the apical area to the centerof the
radiolucencyestablishes drainage and relieves pressure. Once the drainagestops, fibroblastsbegin to proliferate and deposit
collagen; thiscompresses the capillary network,and the epithelialcells are thus starved, undergodegeneration, and are engulfed
by the macrophages.
• Although this proves to be an effectivemethod Shah suggests the possibilitythat quiescent epithelial cellsmay be stimulatedby
instrumentationin the apicalregion, with resultant proliferationand cyst formation, and thus stressed on the need for follow-up
for a period of at least two years.[

50. • Healing of large cysts like well-defined radiolucencies following conservativeroot canal treatmenthas been reported.
• Although the cysticfluid contains cholesterolcrystals, weekly debridement and drying of the canals over a period of two to three weeks, followed by obturationhas
led to a completeresolutionof lesions by 12 to 15 months.
• Decompression technique
• The decompression techniqueinvolves placementof a drain into the lesion, regular irrigation,periodic length adjustment,and maintenanceof the drain, for various
periods of time.
• The drain could either be ‘I’ shaped pieces of rubber dam,polyethylene tube along with a stent, hollow tubes, a polyvinyl tubing,uction catheter[32] or a radiopaque
latex tubing.There is no standard protocol as to the length of time necessary to leave the drain. It may be different for different kinds, sizes or locationsof lesions.It
can vary between two days to five years. Daily irrigationof the lesion can be carried out by the patientthrough the lumen of the drain using 0.12% chlorhexidine.The
advantages of this techniqueare; it is a simpleprocedure, it minimizesthe risk of damaging adjacent vitalstructures,and is easily toleratedby the patient.
• However, several disadvantageshave also been noted; patientcomplianceis very essential,inflammationof the alveolar mucosa, persistenceof the surgicaldefect at
site,development of an acute or chronic infection,displacementor submergence of the drainage tube
• Rees suggestsplacementof a small amount of red wax over the end of the drain to prevent ulcerationof the labialor buccal mucosa adjacentto the drain. The
decompression techniqueis contraindicatedin cases of large dental granulomas or any solid cellular lesion, assince there is an absence of a fluid-filledcavityto
decompress.Active nonsurgical decompression techniqueThis technique uses the Endo-eze vacuum system (Ultradent, Salt Lake, Utah) to create a negative pressure,
which resultsin the decompression of large periapicallesions.

51. NANOCRYSTALLINE HYDROXYAPATITE GRAFT
• nanocrystalline apatites are nonstoichiometric, calcium- (and OH-) deficient. They may incorporate
substituted ions in their nano-sized particles . Specifically, their higher solubility accounts for calcium and
hydroxide deficiencies than hydroxyapatite. Moreover, they are capable of being mature when exposed to
humid environment.. A crucial biological function in bone depends on the small size and non-
stoichiometry of apatite nanocrystals.
• These nanocrystals probably cause mineral phase with the solubility needed for resorption of the bone by
osteoclasts. Therefore, they enable bone mineral to act as an ion ‘reservoir’ capable of either capturing or
releasing ions (or small molecules) under the control of the body to ensure homeostasis.
• Given these unique features, bone is a living tissue, not an inert, which continuously undergoes
remodelling and repairing processes. Synthetic apatite demonstrates good biological properties including
biocompatibility, bioactivity, lack of toxicity or inflammatory, immunity reactions, and a relatively high
bioresorbability.

52. • Different synthetic ways have been utilized to prepare nano-sizedapatite crystals.Yet, preparationof actualbiomimetic
nanocrystallineapatites might be considered as a scientific and technologicalchallenge.
• Thus, the large surface-tovolume ratio, the existenceof a surface hydrated layer, and non-apatiticin nature are important in
the formation procedureof a solution. This layer is bound to disappear progressivelyas the stable apatite domains(in the core
of the crystals) improve with time. Possessing a great ionic mobility, ion exchangeand adsorption capacities allows for
participationof this hydratedlayer in the interactionwith macromolecules .
• Effectsof n-HA on epithelial cells Kawai and colleaguesstated that n-HA might have a therapeutic effect on periodontal
epithelium. Therefore, they conjectured thathealing processof open wound by contractioneffect could be increasedthrough
intravenous calcium-based nanoparticles.Role of n-HA in differentiationand proliferationof periodontal ligament (PDL)
cells
• Kanaya and co-workers [14] observed n-HA could stimulate differentiationof PDL cells, mediatedby mechanosensitive
signalling pathway and expressionof BMP-2. Besides, Yang et al. [15] conductedan animal study through which they found
n-HA could be used as a coating onsilk scaffolds. Thus, they pointed out that n-HAcoated silk scaffoldsmight be potentially
good biomaterialsfor regeneratingperiodontaltissue. Along with the above-mentionedstudies, there are several research
articlesin the extant literature that emphasize n-HA effects on different cells in the periodontium.

53. • Fibroblast Based on the results of a study by Saleh et al. , it was proven that silver n-HA could enhance fibroblast cell maturation and
proliferation. This could eventually result in connective tissue regeneration. In contrast, n-HA was found to be much more
biocompatible than silver nanomaterial in a study of evaluating the biocompatibility of silver and n-HA on fibroblast cells by Shahoon et
al..
• An in vitro study by Sun and colleagues revealed that n-HA could increase proliferation and differentiation of PDL fibroblast cells in
comparison to dense hydroxyapatite. Additionally, it was pointed out that n-HA was more biocompatible than dense HA.
• Osteoblast Shnettler et al. found that n-HA could bind to the bone and stimulate the osteoblasts in the early stage of periodontal defect
repair. This can lead to bone formation. Similar results were found in a study by Thian and co-workers .
• Moreover, Pilloni et al. proved that n-HA can increase the proliferation and differentiation of osteoblasts. In a report by Webster et al.
greater protein adsorption and osteoblastic cells adhesion on n-HA were shown. Liu et al. [23] found that n-HA could stimulate binding
and proliferation of osteoblast-like MG-63 cells. It was proven that n-HA exhibits biocompatibility and minimal toxic effect on
osteoblast cells in studies by Motskin et al.
• Hsieh et al. , and Zhao et al. . Osteoclast In a study by Detsch et al. it was shown that n-HA with low or no carbonate content can
enhance the differentiation of osteoclast-like cells. This can result in having a great number of osteoclast cells on the material compared
to carbonate-rich group. Activated osteoclast recruited mesenchymal cells from the bone marrow to differentiate them into osteoblasts.

54. Effects of n-HA on bone regeneration
• Jahangirnezhad et al. reported that n-HA contains osteoconductiveproperties which make it capable of producing
sufficientamount of bone as bone grafting material.Similarly Vullo et al. indicatedthat n-HA possessesboth
osteoconductiveand osteoinductive properties in periodontal defects in dogs.
• Gotz et al. evaluatedthe immunohistochemical propertiesof hydroxyapatitenanocrystallinesilica gel on biopsies
obtained from jaw bone. The resultsrevealed n-HA had osteoconductive and biomimetic properties. These
propertieswere integratedinto human physiologicalbone turnover at an early stage.By obtaining clinical results
which were comparable to autogenous graft materials
• Huber et al. concluded that n-HA paste was appropriate for filling bone defects.
• Based on a study by Talal et al. n-HA-polylactic acid composite may be a suitablegraft material for guided tissue
regeneration(GTR) membrane. Although this material acts as a barrier, it can enhance bone regenerationvia
delivery of biologicallyactive molecules.These results were supported in a study by Busen et al. [where they
found n-HA could compete with Bio-Oss in bone reconstruction surgeries
• . They found that bone formation in Bio-Oss group was greater than n-HA

55. • A 33-years-oldfemale patientreported to the Department of ConservativeDentistry and Endodontics with a chief complaint
of swelling on the inner surface of gum region in relation to upper front teeth for the past 10 days. Swelling was initially
small, then gradually progressed and was associatedwith discomfort while taking food.
• Clinical examinationrevealedEllis Class IV fracture in 21 with a swelling of 2.5 cm × 2 cm size seen over the palatal
mucosa in relationto 21, 22, and 23 [Figure 1a]. Tendernesswas felt on palpation overthe apical mucosa in relationto 21,
22, and 23. These three teeth were sensitiveto percussion tests.
• Pulp sensitivity tests revealed that 11, 21, 22, and 23 were nonvital. Preoperative intraoral periapical radiograph of 21, 22,
and 23 reveals presenceof large irregularperiapicalradiolucency(3 cm × 2 cm in size) at the apex of 21, 22, and 23 [Figure
2a and b]. This case was planned forconventional root canal treatment followed by periapical surgery.The root canal
treatment was performed using step back technique till anapical size of #50, # 55, #45, and #60 in relationto teeth 11, 21,
22, and 23, respectively.
• .

56. • Sodium hypochlorite (5.25%) solution (Prime Dental Products Pvt. Ltd., Thane, India) was used to irrigate
the canals during the canal preparation. Nearly 2% chlorhexidine solution (ICPA Health Products Ltd,
India) was used as the final irrigant after biomechanical preparation. The root canal treatment was
performed in three visits, and calcium hydroxide was used as the intracanal medicament. The root canals
were obturated using gutta-percha (Dentsply Maillefer, Ballaigues, Switzerland) and AH 26 sealer
(Dentsply DeTrey GmbH, Philadelphia, USA) by lateral compaction technique
• Before planning for the surgical procedure, patient’s platelet count (4 lakh/mm3 ), hemoglobin (12 g/dl),
bleeding time (2.5 min), and clotting time (4.5 min) were assessed and found to be within normal limits.
Informed consent was obtained from the patient. Under local anesthesia (1:200,000 adrenaline, DJ Lab,
India), a full thickness mucoperiosteal flap was reflected by a sulcular incision starting from the distal
aspect of the tooth 12 to distal aspect of the tooth 25 [Figure 2a]. A large periapical defect was seen with
complete loss of labial cortical plate

57. • .
• The lesion measured 2.5 cm, 2 cm, and 2 cm correspondingto the length, width, and depth of the lesion. Tissue curettage
was done at the defect site followed by thorough irrigationusing sterile salinesolution [Figure 2b and c]. Using #702 tapered
fissure bur (SS White Burs), root end resectionwas performed in teeth 11, 21, 22, and 23 [Figure 2d]. Root end cavity of 3
mm depth was prepared with diamond-coatedultrasonicsurgical tip S12 90ND (Satelec/Acteon,Merignac, France) at high-
power setting of ultrasonic device.White mineral trioxide aggregate (MTA) (ProRoot MTA; Dentsply, Tulsa, USA) was
used as the root end filling material. A volume of 10 mL of blood was drawn from the patient’s antecubitalvein and
centrifuged (REMI centrifuge machine Model R-8c with 15 mL swing out head) for 10 min under 3000 revolutions

58. • 400 g) per minute to obtain the PRF. The resultant product consisted of the following three layers: • A cellular
plateletpoor plasma at the top of the tube • Fibrin clot (PRF) in the middle of the tube and • Red blood corpuscles
at the bottom of the tube. PRF was carried and packed into the defect to the level of defect walls
• Flap stabilization was done followed by suturing using 3-0 black silk suture material (Sutures India Pvt. Ltd,
Karnataka,India). Analgesicsand antibioticswere prescribed,and the patient was advised to use 0.2%
chlorhexidine mouthwash for a week. Suture removal was done 1 week later and the healing was satisfactory.
• Patientwas reviewed at 3 months [Figure 3a and b] and 12 months [Figure 3c] during which there were no
symptoms of pain, inflammation, or discomfort.These follow-up visitsincluded routine intraoral, radiographic
examinations,and professionalplaque control. Radiographically, periapicalbone regenerationwas evident at the
end of 12 months [

59. • Discussion Orthograde root canal therapy should be the first option for treatment ofall inflammatoryperiapicallesions which have
85% of success rate. Periapical surgery remains the last resort when orthogradetreatment failsor is not possible. After a surgical
procedure, healingusually occurs by repair or regeneration.
• The four critical factorsthat influence bone regeneration after theperiapicalsurgery are primary wound closure, angiogenesisas a
blood supply and source of undifferentiatedmesenchymalcells, space maintenance, and stabilityof the wound (PASS principle).
• The present case report evaluated theclinical efficacy ofPRF in the treatmentof intrabony defect. PRF is a matrix of autologous
fibrin with a large quantity ofplatelet and leukocyte cytokinesembeddedin it. As the network of fibrin disintegrates, the intrinsic
incorporation ofcytokineswithin the fibrin mesh allows their progressivereleaseover time (7–11 days). The main componentof
PRF is high concentrationof growth factors present in the plateletswhich are required for wound healing.[11-14]

60. • Among the various growth factors, PRF contains PDGF, TGF-β1 and β2, IGF, epidermal growth factor (EGF), vascular
EGF-, and fibroblast growthfactors which are believed to play a major role in bone metabolismand potential regulationof
cell proliferation
• PDGF is an activator ofcollagenasewhich promotesthe strengthof healedtissue. TGF-β activatesfibroblasts to form
procollagenwhich deposits collagenwithin the wound. PRF facilitateshealingby controllingthe local inflammatory
response.
• According to Simonpieri et al.,the use of this platelet and immune concentrateduring bone grafting offersthe following four
advantages:First, the fibrin clot plays an important mechanical role and serves as biological connectorsbetween the bone
particles.Second, the integrationof this fibrin network into the regenerativesite facilitates cellular migration, particularlyfor
endothelial cells necessaryfor the neoangiogenesis, vascularizationand survival of the graft. Third, the platelet cytokines
(PDGF, TGF-α, IGF-1) are graduallyreleasedas the fibrin matrix is resorbed, thus creatinga perpetualprocess of healing.
• Finally, the presence of leukocytes and cytokinesin the fibrin network also plays a significant role in the self-regulation of
inflammatoryand infectiousphenomena withinthe graftedmaterial.

61. • Conclusion- PRF is a healing biomaterial as it contains all the factors required for optimal wound healing.
Previous research and clinical experience indicate that PRF improves early wound closure, maturation of
bone, and the final aesthetic result of the periodontal soft tissues. Long-term follow-up of the present case
and long-term controlled clinical trials will be required to evaluate the final treatment outcome.
Prasanthi NN, ChittemJ, Simpsy GS, Sajjan GS. Surgical management of a large inflammatory
periapicallesionwith platelet-richfibrin. J Interdiscip Dentistry2017;7:76-9

63. Within the parameters of this investigation, the following conclusions were
drawn:
• 1. Wound healing responses of the mucoperiosteal tissuesto incisional wounding in periradicular surgery are remarkably
rapid.
• 2. Few differencesin the temporal and qualitative degreesof healingof incisionalwounds were noted between the two types
of flap designs, althoughthe submarginalrectangularincisionsshowed a less predictablehealingpatternwith greater
intersample variationsin the first 4 postoperativedays.
• 3. The intrasulcularincision leaves a thin layer of vital tissues attachedto supracrestal root surfaces. This root-attached
connective tissue and epithelium are not clinically visible.
• 4. With close flap reapproximation and the formation of a thin fibrin clot in the wound site, apical epithelial downgrowth
along the root surface does not occur if the vitality ofthe root-attachedtissues is maintainedduring and after periradicular
surgery. Thus, loss of soft tissue attachment level following periradicularsurgery with an intrasulcular incision is not
inevitable but is preventable.
• 5. In the presenceof vital root-attachedtissues, the temporal and qualitative woundhealingin the intrasulcularincisional
wound site is essentially thesame as that of other incisionalwounds evaluatedin this study.

64. • 6. Vitality of root-attachedtissuescan be predictably maintained by (a) initiatingreflection and elevationof the
flap in the verticalincision and using undermining elevationto reflect the flap; (b) avoiding curettement or planing
of the supracrestalroot surfaces;and (c) preventing the dehydration of these tissueswith frequent irrigation.
• 7. Preservation of root-attached epithelium promotes rapid epithelialseal formation, and preservationof root-
attached connective tissue enhances connectivetissue reattachment rather than new attachment
• 8. At 14 and 28 days postsurgery,there is essentiallyno difference in the incisionalwound healing progress of the
two flap designs in any of the evaluated or observed biologicalevents of wound healing.
• 9. In vertical incisionalwounds of both flap designs,epithelialclosure occurs rapidly, with a multilayered
epithelialseal established between 24 and 48 h and epithelialbarrier formation occurring between 48 and 72 h.
Collagen synthesisin the wound site also occurs early, with aggregation of The IncisionalWound 435 collagen
macromoleculesto form fibers between 48 and 72 h.

65. • . 10. In horizontal wounds of both flaps designs, epithelial closure is extremely rapid; with a thin epithelial
seal established at 24 h, a multilayered seal between 48 and 72 h, and epithelial barrier formation occurring
between 72 and 96 h.
• Collagen fibers are formed in the wound site between 24 and 48 h.

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