Periodontal Regeneration Past Present and Future

Edward Sammut BChD MSc MClinDent MFDS MRD RCSEd Specialist in Periodontics (UK)

Smile for
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ealth Malta

21 November 2012 OBJECTIVE Descri!e periodontal defects and their relati"e potential for periodontal re#eneration Descri!e periodontal wound healin# and point out $e% differences !etween repair and re#eneration &i"e a historical perspecti"e on periodontal re#eneration techni'ues Descri!e contemporar% techni'ues for periodontal re#eneration and their anticipated outcomes Speculate on future de"elopments in this field

Introdu!tion Periodontal pro!lems are mainl% periodontitis and recession( Both of these processes are dri"en !% inflammation caused !% pla'ue( )n the case of recession the low*#rade inflammation ma% !e caused !% chronic trauma( +he $e% common e"ents are loss of attachment, apical mi#ration of the -unctional epithelium and pla'ue contamination of the root surface(

.ormal Periodontal Structure

Sulcus /unc onal Epithelium Den ne C+a achment Cementum Periodontal 0i#ament 1l"eolar Bone

+he &oals of +reatment

Remo"e pain and sensiti"it% Keep patient2s teeth in function Satisf% aesthetics Pre"ent further attachment loss Remo"e cause of inflammation and esta!lish conditions for it not to return Re#enerate the lost attachment3 Co"er root surface3

1 case was presented showin# e4treme attachment loss in an intra!on% defect mesial to 0R5( Patient had pulp s%mptoms from the tooth and e4traction was considered due to the cost of RC+, perio sur#er% and crown !ein# similar to a dental implant( +he patient declined and simple root surface de!ridement was performed repeatedl%( +he patient demonstrated reduction in poc$et depths, increase in the clinical attachment and radio#raphic !one fill of the defect o"er a two*%ear period( Bone re#eneration is not a new idea( )n 6789: Prichard, /( pu!lished: +he infra!on% techni'ue as a predicta!le procedure( /( Periodontolo#%, 2": ;<;*;65 Sur#icall% e4cised all tissue in the poc$et +in*foil placed to $eep out the wound dressin# Denuded !one was allowed to #ranulate o"er = much li$e a soc$et Predicta!le !one fill seen radio#raphicall% 0ater on, another $e% paper in this field, which is special !ecause it includes re*entr% sur#er%: 6795: Roslin# B, .%man S, 0indhe /, and /ern, B: +he ealin# potential of the periodontal tissues followin# different techni'ues of periodontal sur#er% in pla'ue free dentitions( / Clin Periodontol 6795 #$;>>*;8< Different sur#ical procedures to treat intra!on% defects Re*entr% sur#er% to confirm results 1ccess and apicall% repositioned flaps showed !one fill ?@<A Periodontal defects ma% !e SUPR1BB.C or ).+R1BB.C Supra!on% defects refer to horiDontal !one loss with circumferential attachment loss around a tooth( )t is not currentl% possi!le to consider periodontal re#eneration in the supra!on% situation( )ntra!on% or an#ular defects can !e classified into 6, ; or > walled defects( +hese are #raphicall% represented !elow( Periodontal re#eneration can !e considered in intra!on% defects( +here is a #ood suppl% of cells from !oth the PD0 and the !one which can populate the defect and re#enerate missin# tissue(

1 true re#eneration does not result onl% in the #rowth of new !one in the defect = it also includes #rowth of new cementum on the root surface and new periodontal li#ament fi!res -oinin# the root surface to the new !one( Classic animal models of healin# followin# periodontal sur#er% show us that there is a "er% small amount of true re#eneration and most healin# is !% re%air in which a lon# -unctional epithelium lines the root surface and separates it from the newl% formed !one

Bne*wall defect

+wo*wall defect

+hree*wall defect

Classic 1nimal Models

/ Clin Periodontol( 6795 #:8E*8@( O sseous re%air o& an in&rabon'%o!(et ) it*out ne)atta!*m ent o& !onne!tiv e tissue Caton /&, Fander 1 / Periodontol(G6797 SepH8<(7):E5;*5( T*e atta!*m ent bet) een toot* and g ing iv al tissues a&ter %eriodi! root %laningand so&t tissue !urettag e+ Caton /&, Fander 1( / Periodontal Res 6797 1,:8;<*8;8 Periodontal re%air a&ter redu!tion o& in&lam m ation+ Polson 1M, Kantor ME, Fander 1(

From: Clinical Periodontologyand Implant Den stry4th Ed. ind*e. / arring .andang + Blac$well Mun$s#aard(

+he outcomes which we measure clinicall% = that is pro!in# depth, clinical attachment le"el and radio#raphic !one #ain ma% !e no different in periodontal re#eneration and in periodontal repair( owe"er, re#eneration is a more desira!le outcome !ecause it restores full and functional periodontal structure around a tooth(

REP3IR Bone fill Root surface co"ered with Ilon#J -unctional epithelium .o new li#ament .o new cementum

RE4ENER3TION Bone fill .ew attachment forms .ew li#ament forms .ew cementum co"ers pre"iousl% IdiseasedJ root surface

1lthou#h PD0 is "er% rich in stem cells and PD0 stem cells ha"e the a!ilit% to form all tissues re'uired for re#eneration = this doesn2t happen( 0*' doesn1t t*is *a%%en2 Epithelial down*#rowth alon# the root surface is 'uic$ 0ac$ of adherence of PD0 cells to root surface dentine Karrin#, 0indhe and co*wor$ers did a series of studies to loo$ at healin# processes !etween root surface, !one, li#ament and #in#i"al connecti"e tissue(

+he Karrin# Stor% 67@<*67@E

Bea#le do# series of e4periments E4perimental periodontitis * roots with attachment loss were cleaned, e4tracted and !uried under flaps

Part of root still co"ered in PD0 reattached to !one or #in#i"al tissue Bther IdenudedJ part of root surface de"eloped an$%losis and resorption where in contact with !one or #in#i"al tissue PD0 #rew up the root in a third e4periment where the root was not e4tracted !ut co"ered !% the flap

Followin# these e4periments, the% performed a human e4periment in a landmar$ 67@; paper: 1 patient who was due to ha"e e4traction of 00; was consented to ha"in# a &+R procedure usin# a Millipore mem!rane, and a notch was cut in the root surface to indicate the le"el of the attachment loss( +hree months later the tooth was remo"ed en !loc to#ether with surroundin# tissue( istolo#% confirmed presence of new attachment coronal to the notch on the root, demonstratin# the principle of &+R(

&uided +issue Re#eneration

.%man S, 0indhe /, Karrin#+ and R%lander ( (67@;) .ew a achment followin#sur#ical treatment of human periodontal disease( J Clin Periodontol 5: ;7<*;75

Karious mem!ranes used o"er the %ears .on*resor!a!le &ore*te4 &ore*te4 titanium reinforced Resor!a!le S%nthetic = e# Kicr%l or Resolute Colla#en = e# Bio*&ide Filler material can !e used !elow mem!rane to help maintain space

)ssues with the non*resor!a!le mem!ranes were that the% sometimes !ecame infected and the% also re'uired a second operation to remo"e them( For this reason resor!a!le mem!ranes !ecame more popular( +he definiti"e re"iew is: .eedleman )&, Lorthin#ton K, &iedr%s* 0eeper E, +uc$er R/( 4uided tissue regeneration &or %eriodontal in&ra6bon' de&e!ts+ Cochrane Data!ase S%st Re"( ;<<5 1pr 67H(;):CD<<69;E( 0ar#e "aria!ilit% !etween studies Mean #ain of !lini!al attachment (a"era#ed out o"er the "arious studies) o"er BFD (open flap de!ridement) was 6(;mm .um!er .eeded +o +reat of @ patients = !efore the ad"anta#e

of &+R was o!ser"ed( Karious !one filler materials ha"e !een used o"er the %ears Patient2s own !one (1uto#enous #raft) From a cada"er (1llo#raft, e# Roc$% Mountain) From an animal (Meno#raft, e# Bio*oss) Coralline Calcium Car!onate S%nthetic %dro4%apatite Bioacti"e #lass Beta*tricalcium phosphate Clinicall% these results in an a"era#e reduced PPDs and impro"ed C10s (6*;mm) o"er open flap de!ridement( +he% also produce nice radio#raphs !ecause the materials are t%picall% radio*opa'ue( +he pro!lem is one cannot !e sure if the ima#e is of the radio*opa'ue material or an% newl% formed !one( Meno#raft and s%nthetic particles tend to encapsulate in fi!rous tissue * unless co"ered !% a &+R mem!rane = in which case the filler is a simple space maintainer and the procedure should !e "iewed as a &+R procedure( +rom!elli 0, eitD*Ma%field 0, .eedleman ), Moles D, Sca!!ia 1: 1 s%stematic re"iew of #raft materials and !iolo#ical a#ents for periodontal intraosseous defects( / Clin Periodontol ;<<;H ;7(Suppl( >): 669=6>8( 1 completel% different approach was ta$en at !% Swedish researchers in the late 677<s( )n e4periments loo$in# at tooth de"elopment dentine on its own was insufficient stimulus for follicular cells to differentiate into cemento!lasts( +his challen#ed the understandin# of the process of tooth de"elopment as it was thou#ht that once ertwi# root sheath disinte#rated the presence of the dentine stimulated follicular cells to la% down cementum( )n actual fact, it was found that deposition of enamel matri4 proteins onto a de"elopin# root surface is an essential step precedin# formation of acellular cementum( 1 thin la%er of JenamelJ can still !e histolo#icall% seen !etween cementum and dentine( +he formation of cementum is a critical step in the attachment of periodontal li#ament and formation of al"eolar !one = whether its in tooth de"elopment or in periodontal re#eneration, so enamel proteins were loo$ed at for potential to stimulate periodontal re#eneration( 1 proof of principle stud% e4tracted animal teeth, cut ca"ities in the root surface, then treated the same ca"ities with enamel matri4 proteins and re*planted the teeth( 1cellular cementum formed on the root surfaces in the ca"it% and re* esta!lished periodontal support(

Lithin a short time, Enamel Matri4 Deri"ati"e (EMD) was mar$eted as Emdo#ain !% Biora in Sweden( EMD is purified acidic e4tract of proteins from pi# enamel matri4: 7<A 1melo#enin protein = h%dropho!ic a##re#ates = hi#hl% conser"ed 6<A mi4ture of other proteins = not completel% defined or understood !ut includes proline*rich non*amelo#enins, tuftelin, tuft protein, serum proteins as well as amelo!lastin and amelin Emdo#ain was ac'uired !% Straumann in ;<<>( +he effects of EMD in "itro include Proliferation and #rowth of PD0 fi!ro!lasts )nhi!ition of epithelial cells )ncrease protein s%nthesis !% PD0 fi!ro!lasts Formation of mineraliDed nodules in PD0 f!s &rowth of mesench%mal cells Release of autocrine #rowth factors from PD0 fi!ro!lasts Macropha#es stimulated to produce BMPs 1 case was then shown, showin# successful periodontal re#eneration in a 65 %ear old #irl lateral incisor( +he re#enerated periodontal tissues were a!le to accept orthodontic tooth mo"ement and space closure with almost no loss of papillar% architecture( +he $e% re"iews on EMD are Palmer RM, Cortellini P( Periodontal tissue engineering and regeneration: Consensus report of the Sixth European Workshop of Periodontology. / Clin Periodontol ;<<@H >8 (Suppl(@): @> = @5 Bosshardt DD( Biological mediators and periodontal regeneration: a review of enamel matrix proteins at the molecular and cellular levels. / Clin Periodontol ;<<@:>8 (Suppl @):@9 = 6<8( +rom!elli 0, Farina R( Clinical outcomes with ioactive agents alone or in com ination with grafting or guided tissue regeneration. / Clin Periodontol ;<<@H>8 (Suppl @):669 = 6>8( Cairo F, Pa#liaro U, .ieri M( !reatment of gingival recession with coronally advanced flap procedures: a systematic review. / Clin Periodontol ;<<@H>8 (Suppl @):6>5 = 65;(

Future develo%ments )mpro"ement of sur#ical techni'ues = sur#er% is !ecomin# more and more minimal = this pro#ression shows us the de"elopment of flap

desi#ns o"er ;< %ears( Pa%illa Preservation (+a$ei, 67@8) 7odi&ied8 im%li&ied Pa%illa Preservation (Cortellini, 6777) 7inimall' Invasive urgi!al Te!*ni9ue (Cortellini, ;<<9) ingle Fla% 3%%roa!* (+rom!elli, ;<<7) Minimall% in"asi"e sur#er% has the followin# ad"anta#es Reduction in sur#ical trauma )ncrease of flap and wound sta!ilit% Reduction in sur#ical time )ncrease in sur#ical accurac% Reduced postoperati"e mor!idit% )nterestin#l% if one loo$s at the !ontrol grou%s of studies loo$in# at BFD alone "s BFD N EMD application shows that the results from the BFD procedure !% itself are impro"in# with time(

Le are #ettin# !etter at sur#er%

/ Clin Periodontol( ;<<@ Fe!H>8(;):6>7*E5( Epu! ;<<9 Dec 6>( Is t*ere a tem %oral trend in t*e re%orted treatm ent e&&i!a!'o& %eriodontal reg eneration2 3m eta6 anal' sis o& random i:ed6!ontrolled trials( +u CK, +u#nait 1, Clerehu#h K(

1nother impro"ement which was help !etter periodontal re#eneration treatment is the >D dia#nosis and measurement of defects usin# CBC+ ima#in#( +his comes an increased in"esti#ation cost and a radiation dose( +he ima#es also suffer from metal* restoration artefacts( Bne also needs special software to carr% out >D !one defect measurements( +he future pro!a!l% lies in com!inations of acti"e su!stances with !iomaterials and cell cultures to create IEndo#enous Re#enerati"e +echnolo#%J s%stems( 1cti"e Su!stances &rowth Factors Platelet Rich Plasma Enamel Matri4 Deri"ati"e Biomaterials Scaffolds

Bone &raftOFillers Mem!ranes 1utolo#ous cell cultures

S%stems with com!inations of acti"e su!stances with !iomaterials are alread% in use( +hese include &EM;6 = a com!ination of recom!inant human Platelet Deri"ed &rowth Factor in a !eta*+CP matri4( +his product has licencin# issues in the EU at the minute( 1nother one is BP*6 )mplant which consists of >(>m# rh*BMP*9 with 6# purified !o"ine +%pe ) colla#en( +his product is used in spinal fusion and fracture repair and has promisin# la! and animal periodontal models show !one, cementum and li#ament formation( )n this e4citin# and technolo#ical treatment, its important not to lose si#ht of the !asics = periodontal re#eneration demands patients ha"e #ood control of pla'ue, !leedin#, do not smo$e and are not e4cessi"el% stressed( +he% must also !e a!le to cope with the follow*up re#ime( 1t the tooth le"el one must chose defects which are amena!le to treatment, on teeth with fa"oura!le anatom%(