Battling Biofilms Inovations in Endodontics

10  SPRING SPRING  10 BATTLING BIOFILMS— INNOVATIONS IN ENDODONTICS BY MARI-LOU ROWLEY Computational fluid dynamics, multimedia teaching tools and novel irrigation fluids are among the arsenal of technologies developed and employed by UBC Dentistry professor Markus Haapasalo. They are all part of a multiple attack strategy to eradicate biofilms—pernicious colonies of bacteria that destroy teeth, roots and gums. In the long history of dentistry, endodontics— the treatment of diseases of the t
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  UBC DENTISTRY IMPRESSIONS 13 10  SPRING 12 UBC DENTISTRY IMPRESSIONS     P    H    O    T    O    B    Y    M    A    R    T    I    N    D    E    E Computational uid dynamics, multimedia teaching tools and novel irrigation uids are among the arsenal o technologies developed and employed by UBC Dentistry proessor Markus Haapasalo. They are all part o amultiple attack strategy to eradicate bioflms—pernicious colonies o bacteria that destroy teeth, roots and gums. general—as just one specialty in the eld o medicine, o which research is an integral part.”In collaboration with clinician researchersand industry partners around the world,Haapasalo is at the oreront o this sea-change.Tidal metaphors are apt or what he does. Rootcanal systems resemble complex, microscopicirrigation channels. I bacteria get into thesystem and cause disease o the pulp, or rootinterior that houses the nerves, the circulationin the root is permanently destroyed. Withoutblood fow, the body’s deence system can’tmount a response, and the tooth dies.“This is just one reason why we don’t usesystemic antibiotics to treat root canalinection, since antibiotics need to circulatein the bloodstream to be eective,” he explains.Another reason why antibiotics don’t workis that the lie cycle o biolms is relatively slow, with bacteria multiplying roughly onceper week. In contrast, most antibiotics weredeveloped to kill bacteria grown under optimalconditions, where multiplication occurs onceevery 20 minutes. In the slower ecosystem o biolms, antibiotics are just not eective.In the long history o dentistry, endodontics—the treatment o diseases o the tooth root andpulp—is a relatively new specialty, recognized by the American Dental Association in 1963. Priorto modern root canal procedures, treatmentwas oten extraction and dentures. Despiteadvances in procedures, however, 30 to 50percent o the root canal surace area in many teeth isn’t amenable to mechanical cleaning. Itis too dicult to reach all areas o the canalcrevices, and the bacteria that lurk in them aretoo pernicious. In addition, up to 90 percento endodontic disease is asymptomatic until itreaches the crisis point—a throbbing toothache.At the peak o his career, and at the age o 50, endodontist Markus Haapasalo came toUBC rom Oslo to undertake clinical researchthat is upping the odds or positive patientoutcomes, while reducing pain and discomortand revamping the image o endodonticsor the root canal–phobic. “There have beenremarkable changes in the eld o endodonticsin the past 10 years, resulting in a shit away rom mechanically ocused treatment to amore biological approach,” notes Haapasalo.“I regard endodontics—and dentistry in BATTLING BIOFILMS — INNOVATIONS IN ENDODONTICS SPRING  10 BY MARI-LOU ROWLEY  14 UBC DENTISTRY IMPRESSIONSUBC DENTISTRY IMPRESSIONS 15 SPRING  1010  SPRING Using Technology toThwart Bioflms Perhaps the most challenging aspect o treating root canal inections lies in theubiquitous nature o bacterial biolmsthemselves. Unlike a single species bacteriumthat might be responsible or a throat orrespiratory inection, most bacteria orm incolonies known as biolms. And like mostliving systems, biolms need something to“hang on” to. The thin pink lms that ormat the bottom o a water jug, in the basino a humidier or on a mouthguard arecommon examples o biolms. They consisto numerous types o bacteria that coexist intheir own unique ecosystem—a cocktail o morphotypes intertwined and interdependent.Under the microscope biolms may lookbeautiul, but they wreak havoc with biologicaland even industrial systems.“These bacteria all have specic unctions withintheir ‘bacterial society,’” says Haapasalo. “Evenin non-endodontic environments, antibioticscan be ineective because there are so many dierent species o bacteria, and some haveenzymes that destroy the action o the drug.”Haapasalo and his research team simulatean actual in vivo root canal system and buildbiolm colonies in vitro, in the laboratory setting. Using powerul conocal laserscanning microscopy (CLSM), they are ableto obtain detailed images o biolm structureor analysis. In a recently published study,Haapasalo and his group were the rst tocreate multispecies biolms in vitro thatclosely simulate oral in vivo multispeciesbiolms. In particular, they were the rstgroup to successully cultivate biolm withan abundant growth o corkscrew-shapedspirochete bacteria (see illustration below). Irrigation Key to RootCanal Treatment The shit towards a biological approach totreating root canal disease lies in irrigationo the canal system in order to maximizethe eectiveness o disinection. “This is theimportant strategic or philosophical dierence,”notes Haapasalo. “We now understand that themain benet rom instrumentation is to makeeective irrigation physically possible.”Dental irrigants are chemical fuids thatdissolve inected pulp tissue and attackbacteria. With support rom industry, includingVista Dental and Dentsply among others,Haapasalo’s group studied the eectivenesso dierent irrigants against biolms grownin his laboratory. They helped to improve theeectiveness o the irrigating solutions in tissuedissolution and against biolm bacteria (seeillustration, gures A to D). “Our research isboth basic and translational, which makes itnatural that we have active collaboration withindustry,” Haapasalo says.While traditional approaches use irrigantswith a single active component, Haapasalo isworking to develop a multi-agent approachthat attacks dierent aspects o bacterial cellmembranes. His group has recently patenteda novel irrigation fuid with UBC’s Industry Liaison Oce. Root Canal Fluid Dynamics Computational fuid dynamics is an area o research usually associated with large-scalephenomena and related problems, such asorecasting weather, developing drilling mudand managing hydroelectric systems. But fuidfow problems exist at the microscopic levelo the root canal systems as well. The velocity,distribution, volume and pressure o irrigants,the root canal shape and size, and the type, sizeand insertion depth o needles all complicate theendodontist’s task. In addition, the complexity o root canal anatomy makes it dicult to observehow eectively irrigants fush through the system.“The hydrodynamics o the root canal are very dierent than in macro environments, such as adam on a river or instance, because the ‘banks’in a root canal system are so close together,”Haapasalo explains.In an international collaboration with colleaguesat UBC and in China, Haapasalo developed a3D computational fuid dynamic model o rootcanal irrigation. By testing their virtual modelwith dierent mathematical algorithms, andthen comparing the results with a standardizedabricated model, they were able to validate theirmodel against what happens in a physical setting.“Now that we have ound the right algorithm, wecan start to study in detail how to optimize thephysics o irrigation or eectiveness and saety,”he says. It is a delicate balance; under-irrigationcan leave traces o bacteria, while over-irrigationcan cause tissue damage and even pain.In addition, when someone has an unusually shaped root canal, the instrumentation may notbe able to reach into the root. Haapasalo is alsodeveloping the rst fexible ultrasound needletip or root canal irrigation. The benet wouldbe to reach more dicult congurations andto maximize spreading o the irrigant usingultrasound vibrations.“Eradication o dental biolm requires multipleattack strategies,” says Haapasalo. “Today, thereis a whole new philosophy or cleaning anddisinection o the root canal that is completely dierent rom traditional approaches, and weare working together with industry to developmany novel techniques.”     P    H    O    T    O    B    Y    M    A    R    T    I    N    D    E    E Bioflmtreatedwith2%CHXtreatmentor3min(A);CHX-Plustreatmentor3min(B);2%treatmentor10min(C);CHX-Plustreatmentor10min(D).Green(viablecells);red(deadcells).Anabundantgrowthocorkscrew-shapedspirochetebacteria. Expanding Teaching andLearning A native o Finland, Dr. Haapasalo came toUBC rom Oslo in 2004, ater two previousvisits and ruitul collaborations with ormerScience dean Dr. Barry McBride. Haapasalo’sreputation preceded him, and he continuesto play a very active role in internationalscholarship and teaching. He is editor-in-chie o  Endodontic Topics , and the rst non-USassociate editor o the  Journal o Endodontics .Haapasalo was instrumental in establishingUBC Dentistry’s rst graduate program inendodontics—one o only two in Canada,and the only one in western Canada. Healso developed an interactive DVD-ROM, Endodontics and Traumatology  , a hands-onteaching and learning program now used by universities and dentists around the world.“We are ortunate to have such a strongdentistry aculty and alumni group at UBC,”Haapasalo says. “The dedication and highlevel o proessionalism o BC endodontistsis an important cornerstone o our work hereat UBC. Students, general practitioners and,most importantly, patients in the community reap the benets.” Endodontics Primer Endodontics – One o the nine specialties o dentistry recognized by the American DentalAssociation (rom the Greek endo , or inside,and odons or tooth).Biolm – Colony o numerous, interdependentbacterial species that orm a lm on the tooth,root and gums causing disease and decay.Bacterial Morphology – A single bacterial cellhas three basic types or shapes: bacillus (littlerod), coccus (grain or berry) and spirochete(coiled or helical).  PHOTOS COURTESY OFYUAN GAO, YA SHEN,MARKUS HAAPASALO     P    H    O    T    O    S    C    O    U    R    T    E    S    Y    O    F    Y    A    S    H    E    N PHOTO COURTESY OF YA SHEN, MARKUS HAAPASALO, WEI QIAN ABCD
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