Clinical evidence and Science

Clinical evidence and Science Camlog Implant Systems

Clinical evidence and Science 1 Editorial Introduction The Promote® implant surface Science behind the implant-abutment connections Positional stability of the implant-abutment connection Seal of the implant-abutment connections Load bearing capacity of implant-abutment connections Clinical evidence for the Camlog Implant Systems Long-term success Bone preservation PROGRESSIVE-LINE – First clinical evidence Prosthetic restorations: scientifically based treatment options Loading protocols Edentulous situation Titanium bases Fixation and patient-reported outcomes of restorations Digital workflow Complete list of references 2 3 5 11 13 19 21 25 27 31 33 37 37 40 42 43 46 50 CONTENT

2 Clinical evidence and Science EDITORIAL* Science and Clinics and Industry Albert Einstein once said, «All of science is nothing more than the refinement of everyday thinking» and this is what science is based on, answering questions of our daily life. For us today, as dental implant specialists, these questions ideally arise from our clinical routine. Due to the increasing complexity of science, technologies and requirements for the regulatory approval of medical devices only a concerted approach of the scientist, the clinician and the entrepreneur will enhance the understanding of the parameters influencing the biologic integrity of dental implants. The clinician makes subjective observations leading to a question which science of course pursuits by applying knowledge and methods following a systematic methodology resulting in proven objective observations, the evidence. Ideally these objective observations are transformed into a technological advancement. This can just be the other way around, when technological advancement proofs to be successful in the clinicians´hands. The collection of publications from various prestigious scientists and clinicians predominantly sponsored by the Oral Reconstruction Foundation are displayed in this edition, they symbolize successful concerted activities advancing our knowledge in implantology. *Courtesy of the Oral Reconstruction Foundation. Prof. Dr. Katja Nelson Faculty of Medicine University of Freiburg Prof. Dr. Susanne Nahles Charité – Universitätsmedizin Berlin Fig.1_The development of the CAMLOG® and CONELOG® Implant Systems is based on solid foundation of scientific research 1999 Promote® surface 2002 First SCREW-LINE design 2006 Promote® plus surface 2008 Option Platform switching 2010 CONELOG® connection 1996 Tube-in-Tube® connection

Clinical evidence and Science 3 Importance of scientific documentation of implant systems Pre-clinical and clinical studies and the knowledge gained from them help to understand the interface between the dental implant and the surrounding oral tissues as well as identifying areas where additional scientific research is required. Looking at the past development of dental implants and the history of publications, bone and soft tissue healing around dental implants varied greatly depending on the implant design, implant surface, and the surgical approach. Therefore, the importance of evidence-based implant systems is a prerequisite for predictable clinical outcomes in the practice. The overriding goal must be to maintain the implant longevity for the benefit of the patients. From the beginning on, the Camlog company has set high standards in scientific documentation of all essential properties of their implant systems either independently by their Research and Development department or as a sponsor. Furthermore, their effort in supporting research projects in basic as well as in applied science was strengthened by the establishment of the Oral Reconstruction Foundation (www.orfoundation.org). A lot of topics like bone response to implant treatment, placement and loading time, implant and connection design, Platform-Switching concept, prosthetic treatment, and long-term success were covered in multiple publications and articles in highly ranked international scientific journals. Additionally, new scientific knowledge and findings were the basis of further developments of the CAMLOG® and CONELOG® Implant Systems. The CAMLOG® and CONELOG® Implant Systems are state-of-the-art The CAMLOG® Implant System with its butt-joint Tube-in-Tube® connection is one of the world’s leading implant systems. Since its market introduction in 1999, millions of implants have successfully been inserted to restore the oral situation of the patients both aesthetically and functionally. Over the years, the features of the system have been continuously improved based on the scientific state-of-the-art (Fig. 1). The SCREW-LINE implant geometry came to market in 2002 and is very well scientifically documented. The CONELOG® Implant System, on the other side, offers a patented tapered implant-abutment connection, and features the same outer geometry except for the upper shoulder section as the CAMLOG® Implant System. In 2019, the PROGRESSIVE-LINE design was introduced for both implant systems and covers modern treatment options like immediacy, soft bone, and many more. This product line is currently part of many ongoing clinical investigations. Other features common to both systems include the surface texture, the implant body and thread design, the surgical instruments, and prosthetic parts. Depending on the research question the clinical data obtained from one system could therefore be transferred to the other system. This brochure gives an overview on numerous published scientific articles relating to the CAMLOG® and CONELOG® Implant Systems with the task to help the dentists and clinicians to stay up to date with the latest evidence and applying it effectively in clinical practice. In addition to the publications cited in this brochure, a series of further important literature are named in the separately available ‘Literature Overview’ and of course Camlog as a company continues to invest in ongoing and future research. INTRODUCTION 2013 Full digital workflow (DEDICAM®) 2023 Clinical success – proven a million times 2019 PROGRESSIVE- LINE design

The Promote® implant surface

Clinical evidence and Science 5 Use and development of titanium in implant dentistry In the 1950s, Brånemark et al. discovered that titanium, experimentally implanted into rabbits, was treated as endogenous tissue by the surrounding bone. Further investigations confirmed this phenomenon which was a landmark in dental implantology. The inception of osseointegration as a concept was introduced (1). Commercially pure titanium (or CPTi) with its high mechanical strength combined with excellent corrosion resistance is still the material of choice for endosseous dental implants today. It is recognized as an excellent implant material with high biocompatibility and has been the prime material for clinical use in implant dentistry for more than 40 years. Since then, the morphology and topography of the implant surface has been continuously refined for optimal osseointegration. In the early 90s the first studies on sandblasted, acid etched titanium surfaces showed superior bone-to-implant contact compared to plasma-sprayed and machined titanium surfaces (2). In addition, micro-rough surfaces demonstrated accelerated osseointegrative properties. Sandblasting followed by acid etching may be regarded as the gold standard technique to create micro-rough surfaces (3). The Promote® implant surface The Promote® Surface, a sandblasted and acid et- ched surface, has been developed and applied to Camlog implants for more than 20 years (Fig. 2). It is based on current scientific knowledge and represents the state-of-the-art favoring rapid osseointegration. Results from cell cultures, osteohistology and in pull-out tests as well as clinical studies clearly illustrate this (Fig. 3) (4). A state-of-the-art surface applied to titanium implants by sandblasting and acid etching leading to a positive clinical effect on bone growth and related osseointegration. THE PROMOTE® IMPLANT SURFACE Fig. 2_Scanning electron microscope (SEM) image of the Promote® Surface 10 my

6 Clinical evidence and Science THE PROMOTE® IMPLANT SURFACE Fig. 3_Histological view of buccal crestal bone level preservation and soft tissue attachment at the implant abutment interface of CONELOG® SCREW-LINE implants Promote® plus at 12 weeks in dogs. Courtesy of Prof. Dr. F. Schwarz The Promote® Surface was initially only applied to the implant body of CAMLOG® implants while the implant neck remained untreated (1.4 mm machined surface). In 2006, as addition to the portfolio, the smooth-rough margin was set 0.4 mm from the implant shoulder allowing maximum flexibility of the vertical implant position. The ‘Promote® plus surface’ was introduced. With the market launch of the CONELOG® implants in 2011, the Promote® plus surface was applied all the way up to the implant shoulder (Fig. 4). Characteristics: The CAMLOG® SCREW-LINE implants are available with both the Promote® or Promote® plus surface. Difference is the length of machined neck section: 1.4 mm versus 0.4 mm. The CAMLOG® PROGRESSIVE-­ LINE implants are available with Promote® plus. The CONELOG® implants Promote® plus, have a micro-rough surface up to the implant shoulder. The beveled implant shoulder (45°) on top of the CONELOG® implants is acid etched only (Fig. 4).

Clinical evidence and Science 7 THE PROMOTE® IMPLANT SURFACE Osseointegration with Promote® vs Promote® plus design In general, design changes and developments to improve the formation and maintenance of the soft and hard-tissue structures have systematically been tested in animal studies to prove their stateof-the-art technology. In 2006, the machined surface segment of the CAMLOG® implant neck was significantly reduced from 1.4 mm to 0.4 mm since studies have shown better bone-to-implant contact with rough surfaces. Schwarz et al. (2008) investigated the effect of this design change on crestal bone resorption in a dog study (5). Both implant types were inserted into the mandibles of dogs following the standard protocol for CAMLOG® implants (0.4 mm above the bone crest). Histological evaluation took place after 2 and 12 weeks. Bone changes were found in both implant types after 12 weeks. However, the coarse neck area in the CAMLOG® Promote® implants appeared to have a positive effect on bone formation (bone to implant contact) and crestal bone level change. Data demonstrated that the new surface design efficiently reduced the initial crestal bone changes (6). Vertical positioning of implants: effect of rough-machined border on bone resorption The above results were strengthened by a systematic review of Messias et al.: Provided that the implant neck (machined or micro-rough) is placed endosseous, machined collar implants had higher risk of early failure than micro-rough collar implants and 0.4 mm higher bone resorption (7). Another review by Schwarz et al. evaluated the impact of positioning of the machined collar (8). Derived from their conclusions a clinical expert panel recommended in the Camlog Foundation Consensus Report that the smooth-rough border of the implants should at best coincide with the adjacent alveolar bone and determine the insertion depth to limit the peri-implant bone remodeling (9). Fig. 4_Available implant variations from left to right, CAMLOG® PROGRESSIVE-LINE Promote® plus, CAMLOG® SCREW-LINE Promote® plus, CAMLOG® SCREW-LINE Promote®, CONELOG® PROGRESSIVE-LINE Promote® plus, CONELOG® SCREW-LINE Promote® plus CAMLOG® PROGRESSIVE- LINE Promote® plus CAMLOG® SCREW-LINE Promote® CONELOG® SCREW-LINE Promote® plus CAMLOG® SCREW-LINE Promote® plus CONELOG® PROGRESSIVE- LINE Promote® plus

8 Clinical evidence and Science THE PROMOTE® IMPLANT SURFACE

Clinical evidence and Science 9 1. Brånemark PI, Adell R, Breine U, Hansson BO, Lindström J, Ohlsson A. Intra-osseous anchorage of dental prostheses. I. Experimental studies. Scand J Plast Reconstr Surg. 1969; 3(2):81–100. 2. Smeets R, Stadlinger B, Schwarz F, Beck-Broichsitter B, Jung O, Precht C, et al. Impact of Dental Implant Surface Modifications on Osseointegration. BioMed research international. 2016; 2016: 6285620. 3. Bosshardt DD, Chappuis V, Buser D. Osseointegration of titanium, titanium alloy and zirconia dental implants: current knowledge and open questions. Periodontol 2000. 2017; 73 (1): 22–40. 4. Camlog. The Promote surface – a state of the art titanium surface for implant dentistry 2020: [2 p.]. 5. Schwarz F, Herten M, Bieling K, Becker J. Crestal bone changes at nonsubmerged implants (Camlog) with different machined collar lengths: a histomorphometric pilot study in dogs. Int J Oral Maxillofac Implants. 2008; 23 (2): 335–42. 6. Becker J, Schwarz F, Kirsch A. Improvement of marginal bone adaptation through the new promote plus design. Logo. 2006 (special edition). 7. Messias A, Nicolau P, Guerra F. Titanium dental implants with different collar design and surface modifications: A systematic review on survival rates and marginal bone levels. Clin Oral Implants Res. 2019; 30 (1): 20–48. 8. Schwarz F, Hegewald A, Becker J. Impact of implant-abutment connection and positioning of the machined collar/microgap on crestal bone level changes: a systematic review. Clin Oral Implants Res. 2014; 25 (4): 417–25. 9. Schwarz F, Alcoforado G, Nelson K, Schaer A, Taylor T, Beuer F, et al. Impact of implantabutment connection, positioning of the machined collar/microgap, and Platform-Switching on crestal bone level changes. Camlog Foundation Consensus Report. Clin Oral Implants Res. 2014; 25 (11): 1301–3. References THE PROMOTE® IMPLANT SURFACE KEY TAKE OUTS: PROMOTE® IMPLANT SURFACE The application of the sandblasted and acid etched Promote® Surface on CAMLOG® and CONELOG® dental implants, with a history of more than 20 years, was steadily adapted according to the state-of-the-art. The micro-rough surface increased the bone-to-implant contact and stabilized the marginal bone level compared to machined surfaces. The success of the Promote® Surface was proven in multiple clinical studies (4).

Science behind the implant-abutment connections

Clinical evidence and Science 11 Since the introduction of two-piece dental implants, a lot of different types of implant-abutment connections (IAC) have been put on the market. Nowadays, internal connections are state-of-the-art with few maintenance requirements over time (e.g., retightening of screws). Technically, these are classified as either butt-joint or conical connections. Both types of connection are well-established on the dental implant market and are proven to be clinically successful. A significant impact of one of these connection types on crestal bone level changes lacks documentation (1). Important is a high precision of the connective part of the implant and abutment leading to a stable connection. In addition, the design of the connection must transmit and distribute the masticatory load and provide sealing capacity or at least minimal micromovement. The Tube-in-Tube® connection – CAMLOG® Implant System The well-known Tube-in-Tube® connection characterizing the CAMLOG® Implant System is a butt-joint connection with three symmetrically arranged interlocking grooves on the implant side and corresponding cams on the abutment as positional index design (Fig. 6). The tubular design allows an easy and safe insertion of the abutment into the implant and optimal positioning by the index design. Its special geometric design and precision of manufacturing ensures virtually perfect force and torque distribution as evidenced by some of the following publications. Fig. 7_CONELOG® implant-abutment connection with the index design at the bottom of the taper Fig. 6_Tube-in-Tube®, the CAMLOG® implant-abutment connection with the typical grooves and cams The Tube-in-Tube® butt-joint and the CONELOG® conical connections are well-established on the dental implant market and are proven to be clinically successful. SCIENCE BEHIND THE IMPLANT-ABUTMENT CONNECTIONS Abutment Abutment Abutment screw Abutment screw Conical implant-abutment connection Abutment guide in the implant Abutment guide in the implant Groove/cam design Groove/cam design Implant inner thread Upper inner thread Lower inner thread Implant Implant

12 Clinical evidence and Science The conical connection – CONELOG® Implant System The patented CONELOG® implant-abutment connection features on the implant side a high-precision, deep, conical connection geometry with a coronal self-locking 7.5° internal taper followed by a short cylindrical segment with three symmetrically arranged grooves (Fig. 7). Upon insertion, the abutment is rotated until tactile engagement of the cams in the grooves of the implant (positional index design). The Platform-Switching concept Platform-Switching is one contributing method to preserve the peri-implant hard and soft tissue by increasing the distance between the implant-abutment connection interface and the alveolar crest. The concept is achieved by placing abutments of narrower diameter on implants of wider diameter (Fig. 8). The positive effect on marginal bone levels of this shift was first described by Lazzara and Porter 2006 (2). It is believed that the Platform-Switching concept decreases the effect of inflammatory cell infiltrates on bone resorption. With CAMLOG® implants both the Platform-Switching as well as the platform matching option can be chosen with the respective selection of abutments. With CONELOG® implants the Platform-Switching concept is part of the implant-abutment connection design (integrated Platform-Switching). SCIENCE BEHIND THE IMPLANT-ABUTMENT CONNECTIONS Fig. 8_Platform-Switching concept: abutment with narrower diameter than implant platform

Clinical evidence and Science 13 SCIENCE BEHIND THE IMPLANT-ABUTMENT CONNECTIONS Positional stability of the implant-abutment connection Stability of the implant-abutment connection influences the manufacturing of the superstructure as well as the long-term success of implant-based prosthetic reconstructions. To ensure a precise fit of an implant-supported restoration, the reproduction of the exact abutment position in the patient’s mouth and the laboratory is of fundamental importance. During superstructure fabrication, multiple repositioning of the implant and laboratory components is required. An imprecise connection may impair screw joint stability and result in unfavorable load transmission to the components of the reconstruction. Connection stability depends on the precision of fit, which is influenced by the design of the connection as well as by manufacturing tolerances. Numerous studies have been performed to analyze the connection stability of the CAMLOG® and CONELOG® Implant Systems and to compare both to other implant systems. Rotational fit of the cam-groove index design: mathematical considerations Positional stability of the abutment connected to the implant is ensured by the positional index that functions as an anti-rotation mechanism. Different geometric designs of positional indices are used in various implant systems. One main factor influencing the horizontal stability of the implant-abutment connection is the rotational freedom. A rotational displacement of the abutment may impair the fit of the prosthetic superstructure. A research group at the Charité hospital in Berlin, Germany, evaluated the influence of the geometric design of positional indices on the horizontal position stability of the abutment (Semper et al., 2009) (13). The group performed mathematical analyses for three common geometric designs: regular polygon interface of different vertices (Steri Oss, Astra Tech, Straumann); rounded polygonal patterns (Replace Select implant system), and the cam-groove connection which is used in Camlog’s implant systems. The calculations clearly showed that the geometric design as well as the size of the positional index influence the rotational freedom and thereby the horizontal stability of the abutment. The clearance between the implant wall and the abutment has a major influence on the positional stability emphasizing the importance of the manufacturing tolerances. Based on above findings, Semper et al. (2009) used mathematical analyses and 3D-simulations to directly compare the rotational freedom of the three common positional index designs described above, i.e., regular polygon, rounded polygon as well as the cam-groove pattern (14). They hypothesized that the manufacturing tolerances, geometric pattern and dimensions of the index do not influence the positional stability. The study demonstrated that with an assumed clearance of 20 µm between implant and abutment the bidirectional rotation observed varied depending on the positional index design of the implant system. The largest positional freedom, i.e. worst rotational fit, was calculated for the regular polygonal positional index (varying from 3.0° to 3.7°). A better positional stability was determined with the rounded polygonal pattern (1.9°) (Fig. 9). However, the highest positional accuracy was calculated for the cam-groove design of the CAMLOG® Implant System (1.4°).

14 Clinical evidence and Science Fig. 9_Rotational freedom of regular polygonal patterns, polygon profiles, and other patterns. Measuring points and measuring results of (A) the hexagonal positional index (SteriOss), (B) of the dodecagrammal positional index (Astra Tech), (C) of the octagonal positional index (Straumann), (D) of the polygonal profile positional index (Replace Select), (E) of the cam-groove connection (Camlog). 3D simulation: rotational freedom (F) of the Steri-Oss system (hexagon), (G) of the Astra Tech system (dodecagram), (H) of the Straumann system (octagon), (I) of the Replace Select system, (J) of the CAMLOG® system. Abbreviations: V = width across corners, F = width across flats demonstrated at the implant positional index, K = radius of the bulge, R = radius of the outer arc at the notch of the implant, D = distance from the center of the outer arc of the implant to the rotational axis, d = distance from the center of the inner arc to the rotational axis, S = diameter demonstrated at the implant positional index. (Semper et al. 2009, reproduced with kind permission of Thomson Reuters Corp., USA) B C D E A Fi = 2.683 mm Fa = 2.726 mm Va = 3.147 mm Fi = 2.527 mm Fa = 2.481 mm Vi = 2.872 mm Fi = 3.119 mm Fa = 3.072 mm Vi = 3.402 mm Si = 3.683 mm Sa = 3.628 mm Si = 3.050 mm Sa = 3.020 mm Simulation of rotational freedom of angulated abutments on CAMLOG® Implants With the help of a three-dimensional computer simulation, the same group evaluated clinical relevance of the rotational freedom of angulated abutments on the marginal fit of the prosthetic superstructures (Semper et al., 2010) (15). The horizontal displacement of virtually constructed idealized abutments with different angulations (range from 0 to 20°) was simulated with various degrees of rotational freedom (range from 0.7 to 1.85°) as previously described (14). After quantification of the resulting displacement, a subsequent simulation was performed where the superstructure with different defined internal gaps (5 µm, 60 µm and 100 µm) was positioned pressure-­ less on the displaced abutments. Finally, the resulting marginal gap between the abutment and the superstructure was measured with the software (Tab. 1). This gap depended on the degree of abutment angulation and the rotational freedom. Based on this investigation the authors concluded that the rotation of the abutment is of clinical relevance because of its impact on the marginal fit of the prosthetic superstructure. Again, the precisely manufactured cam-groove index design of the implant-abutment connection seem to support precision-fit prosthetic restorations with little to no post-processing during placement. SCIENCE BEHIND THE IMPLANT-ABUTMENT CONNECTIONS

Clinical evidence and Science 15 Internal gap / abutment angulation Rotational freedom (α/2) 0.7 deg 0.95 deg 1.5 deg 1.65 deg 1.85 deg 5 µm assumed internal precision 0 deg 17 µm 40 µm 183 µm 203 µm 266 µm 5 deg 187 µm 316 µm 578 µm 633 µm 782 µm 10 deg 401 µm 597 µm 1.03 mm 1.17 mm 1.31 mm 15 deg 597 µm 868 µm 1.47 mm 1.66 mm 1.87 mm 20 deg 796 µm 1.11 mm 1.82 mm 2.05 mm 2.33 mm 60 µm assumed internal precision 0 deg 18 µm 23 µm 33 µm 43 µm 45 µm 5 deg 18 µm 23 µm 33 µm 43 µm 45 µm 10 deg 18 µm 23 µm 33 µm 43 µm 45 µm 15 deg 18 µm 23 µm 33 µm 89 µm 316 µm 20 deg 18 µm 23 µm 33 µm 576 µm 802 µm 100 µm assumed internal precision 0 deg 19 µm 25 µm 37 µm 44 µm 50 µm 5 deg 19 µm 25 µm 37 µm 44 µm 50 µm 10 deg 19 µm 25 µm 37 µm 44 µm 50 µm 15 deg 19 µm 25 µm 37 µm 44 µm 50 µm 20 deg 19 µm 25 µm 37 µm 44 µm 162 µm Tab. 1_The size of the marginal fit gap of the superstructures depends on the degree of abutment angulation and rotational freedom ranging from 17 µm to 2.33 mm maximum when the internal precision of the superstructure was 5 µm. A range from 18 µm to 802 µm was observed with an internal precision of 60 µm, and from 19 µm to 162 µm with 100 µm. Based on this investigation the authors concluded that the rotation of the abutment is of clinical relevance because of its impact on the marginal fit of the prosthetic superstructure. (Adapted from Semper et al. 2010) Marginal fit of the superstructure at different assumed internal precisions simulated with different degrees of rotational freedom and abutment angulations SCIENCE BEHIND THE IMPLANT-ABUTMENT CONNECTIONS

16 Clinical evidence and Science Fig. 10_Occlusal view of the five tested implant connections with their characteristic position indices: (A) ITI implant with conical-joint and octagonal positional index, (B) Steri-Oss implant with standard butt-joint and hexagonal positional index, (C) CAMLOG® implant with butt-joint and cam positional index, (D) Astra Tech implant with conical-joint and dodecagram positional index, and (E) Replace Select implant with butt-joint and polygonal positional index. (Semper et al. 2010, reproduced with kind permission of Quintessence Publishing co, Inc, USA) Effect of the connection design on the accuracy of repositioning The theoretical calculations described above (13–15) were also tested in an experimental study. Positional stability of five different implant systems (ITI, Steri-Oss, CAMLOG®, Astra Tech, and Replace Select: Fig. 10) was compared after multiple manual disassembly and reassembly (Semper et al., 2010) (16). Five implants were arranged with varying angles in a stainless-steel model to simulate a typical clinical situation. Abutments were assembled and reassembled manually by three test people for each implant system 20 times by using system-specific screwdrivers. Any rotational, vertical, and canting deviation from the initially determined position was monitored using a coordinate reading machine. Rotational freedom ranged from 0.92 to 4.92 degrees. CAMLOG® connections showed significantly smaller rotational discrepancy than the other systems tested (Fig. 11A). The systems with a horizontal butt-joint displayed significantly lower vertical alterations in position than beveled implant-abutment connections (Fig. 11B). Regarding canting discrepancies, the implant systems did not differ significantly (Fig. 11C). The authors concluded that reposition of rotation-safe abutments on the implants leads to a three-dimensional deviation compared to the initial position and that the accuracy of repositioning is influenced by the geometric design of the implant-abutment interface. SCIENCE BEHIND THE IMPLANT-ABUTMENT CONNECTIONS

Clinical evidence and Science 17 A B C Fig. 11 A–C_(A) Rotational deviations, (B) vertical deviations, and (C) canting discrepancies after repeated detachment and re-attachment procedures. Median values. Pe1, Pe2, Pe3 test persons performing the test procedures. S1 Straumann Tissue Level, S2 Steri-Oss, S3 CAMLOG®, S4 Astra Tech, S5 Replace Select. (Semper et al. 2010, reproduced with kind permission of Quintessence Publishing co, Inc, USA) The mathematical considerations of Semper et al. 2009 described above can be directly transferred to the rotational fit of the CONELOG® connection as the positional index is ensured with the same concept of a cam-groove design. Low manufacturing tolerances combined with the geometric design lead to a high positional stability. Both, the theoretical considerations and the established experimental set-up developed by Semper et al. were used to investigate the positional stability of different implant systems with hand-tightened conical implant-abutment connections, i.e., NobelActive, Bone Level, Ankylos C/X, and CONELOG® (Semper-Hogg et al., 2013) (17). Although malposition of the abutment was found to be possible in all tested implant systems, the values for rotational displacement of the CONELOG® Implant System were significantly lower than the ones of the other three implant systems. The median rotation was 0.25°, and the maximum range was 2.14° in the CONELOG® implants. Since the analytical and experimental results for CONELOG® were in very good agreement, the authors concluded high-precision manufacturing for this implant system. The same experimental setup was used for a subsequent study investigating the influence of torque tightening on the positional stability of different conical implant-abutment connections (Semper et al. 2015) (18). The authors aimed to reveal if tightening of the abutment with a predefined torque during all laboratory and clinical procedures leads to more accurate positioning. The hypothesis had to be refuted since torque tightening caused similar displacements than with hand-tightening. In detail the range of the vertical displacement was higher compared to the hand-tightened implant-abutment complexes evaluated by Semper et al. 2013 (17) and was increased for implant systems with a cone angle >10°. The CONELOG® connection with its cam-groove indexing once more confirmed the lowest rotational freedom supporting the accuracy of fit of the prosthetic restoration (Fig. 12). Superior positional stability of the CONELOG® conical connection SCIENCE BEHIND THE IMPLANT-ABUTMENT CONNECTIONS

18 Clinical evidence and Science Fig. 12_Rotational displacement of six implant systems showing the lowest rotational freedom with the CONELOG® connection (adapted from Semper Hogg et al. 2015) 7 0 1 2 3 4 5 6 Rotation in º CONELOG® Nobel Active Ankylos C/X Astra Tech Straumann Tissue Level Straumann Bone Level KEY TAKE OUTS: STABILITY OF IMPLANT-ABUTMENT CONNECTIONS Stability of the implant-abutment connection is strongly influenced by the precision of fit, the connection design and manufacturing precision. Several research groups analyzed and compared the stability of different implant-abutment connections. The CAMLOG® Tube-in-Tube® connection with its cam-groove index design showed favorable results in these analyses with regard to precision in reproducing the abutment position and rotational fit. Although conical connections may have design-related disadvantages regarding precision of fit (vertical displacement), the CONELOG® implant-abutment connection demonstrated evidence of high-precision manufacturing and superior positional stability when compared to other conical connections. Additionally, the “vertical fit feature” of the system definitely ease the clinical handling of the connection: the impression post is not in contact with the cone during impression taking. The vertical discrepancies – inherent to all conical connections – are reduced by this concept (Fig. 13). Fig. 13_«Vertical fit feature»: no contact of impression post and the cone during impression taking SCIENCE BEHIND THE IMPLANT-ABUTMENT CONNECTIONS

Clinical evidence and Science 19 Seal of the implant-abutment connections Existence of microgaps with every implant-abutment connection Microgaps between the implant and abutment favor microbial colonization of the implant-abutment interface. As a result, endotoxins may penetrate the surrounding tissue and may induce inflammatory processes leading to bone resorption and implant loss. Contrary to earlier publications with limited test possibilities several studies by e.g., Zipprich, Zabler and Rack (3–6) showed microgap formation evident in all implant-abutment connections regardless of their design. Visualizing and proving of the existence of microgaps in the internal conical implant-abutment connections for the first time was achieved by Rack et al. (2010) using synchrotron-based radiography (5). High resolution radiographic images were taken under varying static mechanical loads of up to 100 N on the systems Friadent Ankylos C/X, Ankylos Plus, and Straumann Bone Level. The images showed that the microgap size varied between 1 and 22 µm depending on the applied mechanical load. A subsequent study investigating the microgaps after fatigue loading revealed extended gaps with the possibility of micromovement of the implant-abutment complex (Rack et al., 2013) (6). Seal of the CAMLOG® implant-abutment connection The seal of CAMLOG® implants mounted with abutments was first measured by Steinebrunner et al. (2005) using dynamic loading in a chewing simulation test set-up including alternating load with 2 mm lateral movement on a 30° cusp slope with a force of 120N (7). Within five different implant-abutment connections, the Brånemark, FRIALIT-2, the Replace Select, CAMLOG® and the Screw-Vent, they checked migration of test microbes from the internal area of the connection in a sterile external culture medium during cyclic loading. The CAMLOG® Implant System reached a significantly higher number of chewing cycles than the FRIALIT-2 and Screw-Vent implant systems before microbial leakage was noticed (Fig. 14). A follow-up study by Zipprich et al. (2016) examined the bacterial microleakage from outside into the implant interior during dynamic loading (3). The study team developed a new experimental design to eliminate some limitations of the Steinebrunner test setup and to better simulate the clinical situation. Fourteen different implant systems, one half with conical the other with butt-joint connections, were loaded in a chewing simulator with gradually increased load (0 to 200N with steps of 25N). With the help of a channel drilled into the implant wall the lumen below the implant-abutment connection could be rinsed and analyzed for bacterial contamination after each loading step. The team concluded that in general conical implant-abutment connections showed better seal properties than butt-joint implant-abutment connections. However, the CAMLOG® SCREW-LINE implants tested (one group with Platform-Switching abutments, one group with platform matching abutments) did not show any microleakage in this study setup. SCIENCE BEHIND THE IMPLANT-ABUTMENT CONNECTIONS

20 Clinical evidence and Science Seal of the CONELOG® implant-abutment connection Harder et al. (2012) investigated in-vitro, the leakage of bacterial endotoxins from conical implant-abutment connections in two implant systems (Straumann Bone Level, CONELOG®) (8). The test specimens were inoculated with endotoxin and submerged in human whole blood. Endotoxin leakage was assessed in terms of changes in gene and protein expression involved in inflammatory processes in the blood cells. With both implant systems, leakage could be demonstrated even under unloaded conditions. The authors concluded that based on the study results, the prevailing opinion of a good sealing capacity with conical implant-abutment connections should be reconsidered. Further research with synchrotron radiography by Wiest et al. (2018) with the aim to validate a finite-element simulation revealed microgap formation with CONELOG® implants under loading (9). In all load applications with a force from the side it could be shown that the abutment is canted within the connection leading to gap formation. This study will be used as basis for investigating the impact of specific parameters such as screw pre-load on the micromovements since first modelling showed that the preload or screw mounting force has limited influence on microgap formation. KEY TAKE OUTS: SEALING PROPERTIES OF IMPLANT-ABUTMENT CONNECTIONS In general, butt-joint and conical connections all showed microgaps and micromovements allowing the penetration of bacteria irrespective of the connection design. The CONELOG® and the CAMLOG® implant-abutment connection, however, showed good sealing properties in studies. Therefore, both connections seem to be resistant to bacteria penetration which could also be shown in limited bone resorption over time in various clinical studies (refer to chapter: Clinical evidence for CAMLOG® and CONELOG® implants). 24.300 6 7 6 7 6 N = Screw Vent Camlog Replace Select Frialit-2 Brånemark 1.200.000 1.000.000 800.000 600.000 400.000 200.000 0 172.800 43.200 345.600 64.800 System Chewing cycles Fig. 14_Box plot diagram showing the chewing cycles reached before microbial leakage occurred in the individual systems. … median value. * extreme value. The CAMLOG® Implant System clearly reached the highest mean number of cycles among the tested systems (adapted from Steinebrunner et al. 2005) SCIENCE BEHIND THE IMPLANT-ABUTMENT CONNECTIONS

Clinical evidence and Science 21 Load bearing capacity of implant-abutment connections The design of the implant-abutment connection is of high relevance for the loading capacity as well as for the long-term stability of the peri-implant hard and soft tissues. The following studies give deeper insight into loading capacity of the implant systems. Static resistance of Tube-in-Tube® connection A research group from Hannover, Germany (Dittmer et al., 2011), compared different implant systems in an experimental study (10). On implants, centrally embedded in plastic material, corresponding abutments were placed and tightened with screws according to the manufacturers’ recommendations. A universal testing machine was used to apply a 30° off-axis load linearly increasing until failure. Although all tested implants displayed load-bearing capacities that were considerably higher than average chewing forces, the authors could clearly demonstrate that the connection design had a significant influence on the load-bearing capacity as well as on the failure mode due to static overload. The CAMLOG® SCREWLINE implants with Universal abutments demonstrated favorable results regarding their load-bearing capacity (Fig. 15). Fig. 15_Load-bearing capacity (Fm) versus implant-abutment connection type. Means and standard deviations are given. AST – Astra Tech, BEG – Bego, CAM – CAMLOG®, FRI – Friadent, NOB – Nobel, STR – Straumann (adapted from Dittmer et al. 2011) 1400 0 200 400 600 800 1000 1200 Load bearing capacity Fm [N] AST 768 BEG 1129 CAM 999 FRI 624 NOB 944 STR 606 SCIENCE BEHIND THE IMPLANT-ABUTMENT CONNECTIONS

22 Clinical evidence and Science Steinebrunner et al. (2008) tested the influence of long-term dynamic loading on the fracture strengths of five different implant systems, one with external connection (Brånemark) and four with internal connections (FRIALIT-2, Replace Select, CAMLOG® and Screw-Vent) (11). The test specimens (molar) were subjected to dynamic alternating loading for a maximum of 1.2 million cycles in a dual axis chewing simulator before maximum loading was applied for fracture strength determination. The results demonstrated that the CAMLOG® and the Replace Select implant systems with deep internal tube-intube connections with cam-slot fixations had the highest fracture strength score (Tab. 2 and Fig. 16). During chewing, grinding and/or clenching not only axial forces occur on the crowns but also rotational torque which can lead to fractures. Using a torsion testing device Watanabe et al. (2015) investigated the torsional strength of CAMLOG® implant-abutment connections (12). Six specimens of each diameter (3.3, 3.8, 4.3, 5.0, 6.0) were tested with a rotational speed of 3.6°/min until deformation or fracture occurred. The device registered the maximal torque and the torsional yield strength, and each specimen was examined by scanning electron microscope after being tested. The implant diameters 3.3, 3.8, and 4.3 had comparable mean fracture torques. However, these were statistically lower than the ones of the diameters 5.0 and 6.0. The implant diameter and thickness of the implant wall seem to have a direct influence. The microscopic evaluations additionally revealed that the implants including indexing grooves remained intact while the notches of all the abutments were destroyed meaning that in the event of excessive torque the implant remained intact and most probably would not need to be explanted. Dynamic resistance (fatigue resistance) of Tube-in-Tube® connection Torsional resistance of Tube-in-Tube® connection Sc dynB Sc contrB Ca dynB Ca contrB Re dynB Re contrB Fr dynB Fr contrB Br dynB Br contrB 2000 1750 1500 1250 1000 750 500 250 0 Subgroups Fracture loads (N) ** ** Fig. 16_Box plot diagram of the quasistatic fracture strengths of the five tested implant systems: Br – Brånemark, Fr – Frialit-2, Re – Replace Select, Ca – CAMLOG®, Sc – Screw-Vent. dyn = after chewing simulation using dynamic loading; contr = without dynamic loading (adapted from Steinebrunner et al. 2008) Tab. 2_Survival rates of eight implants from each group in the dynamic, alternating loading test. The test was ended after 1 200 000 cycles (adapted from Steinebrunner et al. 2008) survival rates loading cycles failure [n] Replace Select 1.200.000 ± 0 0 Camlog® 1.200.000 ± 0 0 Branemark 954.300 ± 121.014 3 Compress 922.800 ± 102.242 3 Screw-Vent 913.200 ± 102.242 6 Frialit-2 627.300 ± 164.097 6 SCIENCE BEHIND THE IMPLANT-ABUTMENT CONNECTIONS

Clinical evidence and Science 23 KEY TAKE OUTS: LOAD BEARING CAPACITY The CAMLOG® Tube-in-Tube® connection demonstrated a very favorable load capacity under static as well as dynamic test simulations. The connection has proven to transfer and distribute more than the average chewing forces and to protect the implant from possible failure. 1. Schwarz F, Hegewald A, Becker J. Impact of implant-abutment connection and positioning of the machined collar/microgap on crestal bone level changes: a systematic review. Clin Oral Implants Res. 2014; 25(4): 41–25. 2. Lazzara RJ, Porter SS. Platform-Switching: a new concept in implant dentistry for controlling postrestorative crestal bone levels. Int J Periodontics Restorative Dent. 2006; 26 (1): 9–17. 3. Zipprich H, Miatke S, Hmaidouch R, Lauer HC. A New Experimental Design for Bacterial Microleakage Investigation at the Implant-Abutment Interface: An In Vitro Study. Int J Oral Maxillofac Implants. 2016; 31(1): 37–44. 4. Zabler S, Rack T, Rack A, Nelson K. Fatigue induced deformation of taper connections in dental titanium implants. Int J Mat Res. 2012; 103 (2): 207–16. 5. Rack A, Rack T, Stiller M, Riesemeier H, Zabler S, Nelson K. In vitro synchrotron-based radiography of micro-gap formation at the implant-abutment interface of two-piece dental implants. J Synchrotron Radiat. 2010; 17 (2): 289–94. 6. Rack T, Zabler S, Rack A, Riesemeier H, Nelson K. An in vitro pilot study of abutment stability during loading in new and fatigue-loaded conical dental implants using synchrotron-based radiography. Int J Oral Maxillofac Implants. 2013; 28 (1): 44–50. 7. Steinebrunner L, Wolfart S, Bossmann K, Kern M. In vitro evaluation of bacterial leakage along the implant-abutment interface of different implant systems. Int J Oral Maxillofac Implants. 2005; 20 (6): 875–81. 8. Harder S, Quabius ES, Ossenkop L, Kern M. Assessment of lipopolysaccharide microleakage at conical implant-abutment connections. Clin Oral Investig. 2012; 16 (5): 1377–84. 9. Wiest W, Rack A, Zabler S, Schaer A, Swain M, Nelson K. Validation of finite-element simulations with synchrotron radiography – A descriptive study of micromechanics in two-piece dental implants. Heliyon. 2018; 4 (2): e00524. 10. Dittmer S, Dittmer MP, Kohorst P, Jendras M, Borchers L, Stiesch M. Effect of implant-abutment connection design on load bearing capacity and failure mode of implants. J Prosthodont. 2011; 20 (7): 510–6. 11. Steinebrunner L, Wolfart S, Ludwig K, Kern M. Implant-abutment interface design affects fatigue and fracture strength of implants. Clin Oral Implants Res. 2008;19(12):1276-84. 12. Watanabe F, Hiroyasu K, Ueda K. The fracture strength by a torsion test at the implant-abutment interface. Int J Implant Dent. 2015; 1 (1): 25. 13. Semper W, Kraft S, Krüger T, Nelson K. Theoretical considerations: implant positional index design. J Dent Res. 2009; 88 (8): 725–30. 14. Semper W, Kraft S, Krüger T, Nelson K. Theoretical optimum of implant positional index design. J Dent Res. 2009; 88 (8): 731–5. 15. Semper W, Kraft S, Mehrhof J, Nelson K. Impact of abutment rotation and angulation on marginal fit: theoretical considerations. Int J Oral Maxillofac Implants. 2010; 25 (4): 752–8. 16. Semper W, Heberer S, Mehrhof J, Schink T, Nelson K. Effects of repeated manual disassembly and reassembly on the positional stability of various implant-abutment complexes: an experimental study. Int J Oral Maxillofac Implants. 2010; 25(1): 86–94. 17. Semper-Hogg W, Kraft S, Stiller S, Mehrhof J, Nelson K. Analytical and experimental position stability of the abutment in different dental implant systems with a conical implant-abutment connection. Clin Oral Investig. 2013; 17 (3): 1017–23. 18. Semper-Hogg W, Zulauf K, Mehrhof J, Nelson K. The Influence of Torque Tightening on the Position Stability of the Abutment in Conical Implant-Abutment Connections. Int J Prosthodont. 2015; 28 (5): 538–41. References SCIENCE BEHIND THE IMPLANT-ABUTMENT CONNECTIONS

Clinical evidence for the Camlog Implant Systems

Clinical evidence and Science 25 Importance of well-documented implant systems Generally, clinical data showing the performance and safety of the medical devices are a regulatory prerequisite for device approval. In implant dentistry the most important and at the same time the most investigated parameters are the survival and the success rates of implant restorations. Implant related factors such as peri-implant bone remodeling and bone loss, periimplantitis, mobility/stability, and adverse events like pain, infection etc. are taken to evaluate the implant success (Buser et al 2002 (1), Albrektsson et al. 1986 (2)). Long-term clinical data represents a reference in terms of safety and confidence not only for the user but also for the patient. A large number of clinical studies have been performed documenting Camlog’s implant systems with its Promote® Surface in several indications and treatment options. They have confirmed excellent peri-implant clinical outcomes related to soft and hard tissues. Both, the CAMLOG® and CONELOG® Implant Systems are considered well-documented implant systems within the scientific community. Long-term clinical data confirm the safety, performance, and effectiveness of CAMLOG® and CONELOG® implants. CLINICAL EVIDENCE FOR CAMLOG® AND CONELOG® IMPLANTS

26 Clinical evidence and Science Authors Year Follow-up time (year) Total Implants CAMLOG® Implants Survival in % Comments Retrospective studies Knöfler et al. 2017 20 10165 1,4 6063 SL 3.15 loss rate* Knöfler et al. 2019 20 10165 1,4 6063 SL 1.56 loss rate* Camlog® over 10 years period (2001–2011) Lee et al. 2019 12 19006 1,3,4 1317 SL 99.2 at 5-year 97.7 at 10-year Survival related to implant fracture Seemann et al. 2017 7 69377 1 69377: 11220 RL, 58157 SL 2.78 return rate Return rate of total sold implants (complaint statistics) Semper et al. 2008 6 464 1 464: 411 RL, 53 SL 99.6 Nelson et al. 2008 5 532 1,2 463: 410 RL, 53 SL 99.4 Semper et al. 2007 5 448 1,2 403: 363 RL, 40 SL 99.8 Prospective clinical studies (cohort studies) Vanlioglu et al. 2014 10 253 1 253 SL 100 Strietzel et al. 2007 5 333 1 333 SL 98.5 Beschnidt et al. 2018 5 271 1 271 SL 98.6 Krennmair S et al. 2018 5 284 1 284 SL and RL 99.3 Krennmair S et al. 2019 5 295 1 295 SL 99.3 De Lange et al. 2010 5 774 1 774 SL 96.7 Randomized clinical trials Waller et al. (5) 2020 7.5 28 1 28 SL 100 Messias et al. 2019 5 146 1 146 SL 96.6 RL = Root-Line; SL = Screw-Line *Total implants observed vs lost implants (1) CAMLOG®, (2) Straumann, (3) Biohorizons, (4) Others Tab. 3_Publications reporting mid-term and long-term survival rates of the CAMLOG® Implant System. CLINICAL EVIDENCE FOR CAMLOG® AND CONELOG® IMPLANTS

Clinical evidence and Science 27 Meta-analyses of studies evaluating the survival of dental implants in general reported survival rates of 97.2% after 5-year follow-up and 95.2% (Jung et al. 2012 (3)) or 96.4% (Howe et al. 2019 (4)) after 10-year follow-up. The performance of CAMLOG® implants in the mid- and long-term are absolutely in line with or even exceeding these survival rates. Table 3 summarizes retrospective, cohort, and randomized clinical studies evaluating CAMLOG® implants with a followup time of more or equal to 5 years (Tab. 3). Performance in daily dental practice: observational studies In observational studies the use and the performance of dental implants can be examined in daily dental practice and over the entire range of indications. This real-life data is of great importance for the assessment of dental implants by dental professionals. The following three studies include survival and success data from CAMLOG® implants used in broad indications and in both the maxillary and the mandible. In an evaluation of patient/implant data from three dental practices Knöfler et al. reported clinical data of more than 10 000 implants from different manufacturers (mainly Camlog, Friadent, Astra-Tech) and over a period of 20 years (1991 to 2011) (6–8). The study team published three articles focusing on different influencing factors on the implant survival. Camlog implants were only introduced and used starting from 1999/2000. However, 6 063 implants evaluated were CAMLOG® and CONELOG® SCREWLINE implants (60% of all implants analyzed). Demography, implant dimensions and type, indication, type of restoration, treatment plan, and complications were collected. Cumulative survival rates of all involved implants were 96%, 93%, and 86% after 5-, 10-, and 20-years, respectively, and the overall loss rate 4.54%. Camlog implants, however, had a far lower loss rate of 1.56%. General finding was that newly introduced implant systems required the practitioners to undergo a learning curve with the new system and that half of the lost implants were early failures, and the second half was usually lost due to periimplantitis (Knöfler et al. 2019 (7)). The Camlog implants did not show significant differences in survival rates regarding diameters and lengths. Additionally, Camlog implants with its Promote® Surface showed the highest probability of survival compared to other implant systems (Knöfler et al. 2017 (6)). In the third article the investigators looked at the influence of the type of restorations on implant survival: cemented vs. screw-retained; fixed versus removable prosthesis; single crowns, fixed partial dentures, full arch dentures. Single crowns had the lowest loss rate but the paper summarized all possible restorations performed well with low complication rates. (Knöfler et al. 2018 (8)). In a multicenter observational clinical study with a follow-up of 5-years post-loading the survival and success rates of CAMLOG® SCREW-LINE implants, either restored with Platform-Switching abutments or platform matching abutments were observed (Beschnidt et al. 2018 (9)). The implant treatment had to follow the intended use but was open regarding type of surgery and restoration workflow. Patients were recruited in 17 private practices distributed over five European countries. 185 patients with 271 implants could be enrolled whereof 137 patients with 200 implants attended the final 5-year follow-up visit. Three implants were lost post-loading leading to a survival rate of 98.6%. One more persisting complication (periimplantitis) is reflected in the success rate of 98% (criteria by Buser et al. 2002 (1)). The authors attributed excellent clinical outcomes to the implants comparable with those achieved in controlled clinical trials. Vanlioglu et al. (2014) (10) summarized on a congress poster presentation 10-year post-loading follow-up data of 67 patients with 253 implants placed in the posterior maxilla and mandible. Restorations included single crowns and fixed partial dentures. The cumulative survival was 100%. Only a few technical complications within the fixed partial dentures occurred (success rate 96.9%). Mean marginal bone level change was reported with 0.35 ± 0.11mm at 10-year post-loading. Excellent long-term success and survival with CAMLOG® implants Long-term success CLINICAL EVIDENCE FOR CAMLOG® AND CONELOG® IMPLANTS

RkJQdWJsaXNoZXIy MTE0MzMw