Laser-Lok Clinical Overview

Science-based products Game-changing Innovation Unparalleled ServiceEsthetics enhanced by biotechnologyBioHorizons has a proud history of introducing products based on science and evidencebased research. The introduction of Laser-Lok microchannels onto our implants is thelatest example of this tradition. Laser-Lok is a precision laser collar surface treatment developedfrom over 15 years of in vitro, animal and human studies at leading universities. Through this scientificresearch, Laser-Lok has been uniquely shown to attract a physical connective tissue attachment to apredetermined zone on the implant while inhibiting epithelial downgrowth and preserving the coronal level of bone.1Innovative options. not compromisesNo single implant design is perfect for every indication, soBioHorizons provides clinicians a wide variety of implantoptions to meet their requirements and the needs of theirpatients. No other company offers more choicesof body design, connection or surface treatment.All BioHorizons implants and components areprecision manufactured to the tightest mechanicaltolerances in the industry. This yields productswith a form, fit and function you have toexperience with your own hands to appreciate.Patient satisfaction: DeliveredHappy patients are the driving force of successful dental practices, and cliniciansknow they don’t want implants; they want teeth. But traditionally, companies haveonly guaranteed their implants!Beginning in 2008, restorations made on our implants at select laboratoriesusing an approved treatment plan are guaranteed for life. If the prosthesis fails,BioHorizons covers the cost of the rework no red tape, no small print.This is just one example of the world-class customer service you can expectfrom BioHorizons.

Study ReviewThe following review presents some of the studies and presentations related to Laser-Lok microchannels.ResearchIntroResearch OverviewLaser-Lok technology summaryPage 2-3Enhance bone integrationPage 4Control structure of attached tissuePage 5FEAFinite Element Analysis (FEA)Reduce crestal bone stressesPage 6In VitroIn Vitro Research SummaryAltered morphologies, directional growthPage 7Microgrooves induce contact guidancePage 8Suppress Fibrous Encapsulation3 to 12 micron microgeometries vs. random blasted surfacesPage 9Cell Orientation & Organization2 and 12 micron linear grooves vs. diamond patterns, controlled Page 10Inhibit Cell Growth1¾ to 12 micron microgrooves, controlledPage 11Bone Cell Contact Guidance8 and 12 micron microgrooves vs. random blasted surfacesPage 12Directed Tissue Response8 and 12 micron parallel grooves vs. square posts, controlledPage 138 and 12 micron parallel grooves vs. square posts, controlledPage 14Improve Soft Tissue IntegrationRabbit calvarial model, controlledPage 15Control Cell IngrowthCanine implantable chamber, controlledPage 16AnimalIncrease Bone & Tissue Attachment Canine mandible, controlledPage 17Reduce Bone LossCanine mandible, vs. machined and macro grooved implantsPage 18Immediate implant placement and provisionalizationPage 19Immediate, provisional load histologyPage 20Immediate, provisional load histology with sinus graftPage 21Human Histological Evidence of a connective tissueattachment to a dental implantPage 22Prospective double-blinded case series (1 year follow-up)Page 23Prospective, controlled, multi-center (3 year follow-up)Page 24Prospective, randomized vs. Nobel and 3i (3 year follow-up)Page 25Long-tern case studies (8 year follow-up)Page 26Human StudiesHuman Clinical Evidence

Laser-Lok TechnologyLaser-Lok microchannels are a series of precisionengineered cell-sized channels laser-etched ontothe collar of BioHorizons dental implants. Thispatented surface is unique within the industryas the only surface treatment shown to achieveconnective tissue attachment as well as attachand retain both hard and soft tissue.Laser-Lok microchannels are the result of over15 years of research and documented studiesat leading Universities. As part of the research,numerous in vitro, animal and human studieswere conducted to (1) understand how bone andsoft tissue cells react to various types of surfacegeometries and (2) evaluate how specific surfacemicrogeometries affect crestal bone and thebiologic width around dental implants.Microchannels viewed using scanning electron microscopy (SEM) at 1000XIn vitro researchCellular activity was studied on a variety of surface finishes including smooth,roughened and specifically engineered microgeometries. The engineeredmicrogeometries were designed in a variety of repeating patterns and in anumber of different sizes. Through various cell model designs, it was shown alinear grooved pattern in the range of 8 to 12 microns was optimal for inhibitingcell growth,2 maximizing cellular contact guidance3 and providing a directedtissue response.4smoothsurfaceIn vivo validationA series of animal studies (rabbit and canine) were conducted in both animplantable chamber model (intended to assess biologic response) and adental model to assess the differences in tissue response to an engineeredmicrogeometry versus other commonly used surfaces. Through these studies,it was shown a microchannel pattern of 8 to 12 microns improved soft tissueintegration,5 controlled cell ingrowth,6 increased bone and tissue attachment7and reduced bone 19onatisulusbropncaefiibInh9719Human bronchial epithelial cell colony on smooth and microchannel surfacesiontizathowrglelit cLaser-Lok surfacell oCeoitatnrien&00anorg022020Laser-Lok development timeline esperuissttedceDirseonarllulCe0220uct gntacotgracenidaoftsveproIm0320tee inutissIeeasncrueisste&nbotenionmachatt

Laser-Lok TechnologyClinical evidenceTo evaluate how dental implants treated withthe Laser-Lok microchannels benefit patients,a series of human histologic case studies andprospective controlled studies have beenconducted. In a prospective, controlled multicenter study conducted by the Group for ImplantResearch in Italy, it was shown, at 37 monthspost-op, the mean crestal bone loss for implantswith Laser-Lok microchannels was only 0.59mmversus 1.94mm for non Laser-Lok implants. TheLaser-Lok treated implants formed a stable softtissue seal above the crestal bone.9Colorized SEM showing human evidence of connective tissue attachment1High magnification identifies the apical extent of thejunctional epithelium (black arrow)1SEM showing high degree of 0teiultmd,e,ctivo7m3(rn-ceylogadl sst tisoftohisvaic etens)lletronocIn another study, SEM analysis and humanhistology revealed Laser-Lok can produceconnective tissue attachment which appearsto be instrumental in preserving the alveolarbone crest and inhibiting apical migration ofthe epithelium.1 A prospective, double-blindcase series was also conducted where twoLaser-Lok implants and two Nobel ReplaceSelect implants were placed in the anteriormandible of 15 patients. One of each typewas loaded with an overdenture and one ofeach type remained unloaded. At one year,pocket depth and crestal bone loss werestatistically significant less for the Laser-Lokimplants regardless of whether the implantswere loaded or unloaded.10adl loaionvisproucedRe20 o0820tenmachattear8yelobs. Ndvzemiondae, uase

CLINICAL OVERVIEWBone Response to Laser Microtextured SurfacesJL Ricci, J. Charvet, S.R. Frenkel, R. Change, P. Nadkarni, J. Turner and H. Alexander.Bone Engineering (editor: JE Davies). Chapter 25.Published by Em2 Inc., Toronto, Canada. 2000.X-Axis Growth between 4 and 8days (mm)RTF Cell X-Axis Growth14C-D122-XFigure 1. Graphs ofX-axis growth by RTFcells on microgroovedsurfaces after 8 dayscompared to controlcolonies (diameterincrease).4-X10866-X8-X12-X420RTF Cell Y-Axis GrowthY-Axis Growth between 4 and 8days (mm)87C-D2-Y64-Y56-Y438-Y12-YFigure 2. Graphs ofY-axis growth by RTFcells on microgroovedsurfaces after 8 dayscompared to controlcolonies (diameterincrease).210Figure 3. Lightphotomicrographof RTF cellsgrowing on a 12µm microgroovedculture surface.Cells are attachedto tops, bottomsand sides ofgrooves. Cells arealigned along thelong axis of thesubstrate.Figure 4. Scanningelectron micrographof RTF cellsgrowing on a 2µm microgroovedculture surface. Cellsare attached to topsof grooves and spanseveral grooves.Cells are alignedalong the long axisof the substrate.Bar 100 µm.INTRODUCTIONTissue response to any implantable device has been found to correlate with a complex combination of material interface parameters based oncomposition, surface chemistry, and surface microgeometry. The relative contributions of these factors are difficult to assess.In vitro and in vivo experiments have demonstrated the role of surface microgeometry in tissue-implant surface interaction although no well-definedrelationship has been established. The general relationship, as demonstrated by in vivo experiments on metallic and ceramic implants indicatesthat smooth surfaces promote formation of thick fibrous tissue encapsulation and rough surfaces promote thinner soft tissue encapsulation andmore intimate bone integration. Smooth and porous titanium surfaces have also been shown to have different effects on the orientation of fibroustissue cells in vitro. Surface roughness has been shown to be a factor in tissue integration of implants with hydroxyapatite surfaces, and to altercell attachment and growth on polymer surfaces roughened by hydrolytic etching. Roughened surfaces have also shown pronounced effects ondifferentiation and regulatory factor production of bone cells in vitro. Defined surface microgeometries, such as grooved and machined metalsand polymer surfaces have been shown to cause cell and ECM orientation in vivo and can be used to encourage or impede epithelial downgrowthin experimental dental implants. Surface texturing has also been shown to adhere fibrin clot matrix more effectively than smooth surfaces,forming a more stable interface during the collagenous matrix contracture that occurs during healing. This is an effect which may be important indetermining early events in tissue integration.It is likely that textured surfaces work on several levels. These surfaces have higher surface areas than smooth surfaces and interdigitate withtissue in such a way as to create a more stable mechanical interface. They may also have significant effects on adhesion of fibrin clot, adhesionof more permanent extracellular matrix components, and long-term interaction of cells at stable interfaces. We have observed that, in the shortterm, fibrous tissue cells form an earlier and more organized collagenous capsule at smooth interfaces than at textured interfaces. We suggestthat textured surfaces have an additional advantage over smooth surfaces. They inhibit colonization by fibroblastic cell types that arrive early inwound healing and encapsulate smooth substrates.We have investigated (1) the effects of textured surfaces on colony formation by fibroblasts, and (2) the effects of controlled surface microgeometrieson fibroblast colonization. Based on these results, we have designed, fabricated, and tested titanium alloy and commercially-pure titaniumimplants with controlled microgeometries in in vivo models. These experimental surfaces have highly-oriented, consistent microstructures whichare applied using computer-controlled laser ablation techniques. The results suggest that controlled surface microgeometry, in specific sizeranges, can enhance bone integration and control the local microstructural geometry of attached bone.

John L Ricci, Harold Alexander.Key Engineering Materials, Vols 198-199 (2001) pp. 179-202.Trans Tech Publications. Switzerland.Figure 1. Medium power scanning electron micrograph (backscatteredelectron imaging mode) of a bA surface showing the blast-inducedroughness and embedded blast residue as dark inclusions in the surface.Bar 100µm.Figure 2. Medium power scanning electron micrograph of a prototype dentalimplant with the upper 1mm of the collar microtextured with the MG12 surface.Bar 100µm. (From Ricci et al., in Bone Engineering, ed. JE Davies, Em² Inc.Toronto, Ont. Canada, 2000 reprinted with permission.INTRODUCTIONThe success or failure of bone and soft tissue-fixed medical devices, such as dental and orthopaedic implants, depends on a complexcombination of biological and mechanical factors. These factors are intimately associated with the interface between the implant surface andthe surrounding tissue, and are largely determined by the composition, surface chemistry, and surface microgeometry of the implant. Therelative contributions of these factors are difficult to assess. This study addresses the contribution of surface microtexture, on a controlledlevel, to tissue integration.In this paper, we will describe the common machined, blasted, and etched surfaces used on dental and orthopaedic implants, and describe thedevelopment and testing of a series of new laser micromachined surfaces for use on these implants. In previous in vitro experiments, we haveinvestigated (1) the effects of textured surfaces on colony formation by fibroblasts, and (2) the effects of controlled surface microgeometries onfibroblast colonization. Based on these results, we have designed, fabricated, and tested laser microgrooved surfaces with features in specificsize ranges, which are applied using computer-controlled laser ablation techniques. We have tested these on titanium alloy and commerciallypure titanium implants in in vivo models. These experimental surfaces have highly-organized and oriented microstructures. They can beproduced with features in specific size ranges, and can be applied to specific, highly controlled areas of implants. The results suggest thatcontrolled surface mi