Geistlich News - Edition 01-2020 (English)

Page 1

GEISTLICH BIOMATERIALS

Photo: ©gettyimages.ch / Westend61

VOLUME 15, ISSUE 1, 2020

FOCUS PAGE 10

OUTSIDE THE BOX PAGE 24

OUTSIDE THE BOX PAGE 34

Prevention by Regeneration.

Phenotype Modification Therapy.

Out of the palate.

Are there smart ways to prevent foreseeable damage and save surgical time?

This new approach was discussed in a Best Evidence Consensus. What does it stand for?

Our comic shows how to treat recession defects minimally invasive: the VISTA-X technique.


LEADING REGENERATION.

100

GEISTLICH NEWS 1-2020


Editorial

Early intervention beats a rescue mission “Wouldn’t it make better sense to help a patient, before problems occur in the first place?” This idea is brought up by Prof. Kenneth Kornman and Dr. Richard Kao, who describe the benefit of so-called Phenotype Modification Therapy (PhMT) in our interview. The question vividly illustrates the core topic of this Geistlich News issue: regenerative treatments which are preventive, not corrective! Through numerous contributions and interviews from experts, this Geistlich News issue gives you an abridged version of particularly interesting and relevant aspects of preventive care.

Prof. Jeong Hye Kim (KOR) and Dr. Alfonso Rao (UK) report on studies and their clinical experience in soft tissue regeneration. Geistlich Mucograft® and Geistlich Fibro Gide® make valuable contributions toward improving clinical success; contributions you should be aware of. Dr. Hector Rios (USA), an expert in periodontology, who sees orthodontic treatment as an interdisciplinary field, sheds light on a rather different aspect, which should be the subject of special attention in the future. His interview explains briefly and concisely the challenges of orthodontic treatment and how biomaterials can help enhance treatment outcomes. All this and much more is to be found in this new, extremely varied edition of Geistlich News. So we wish you exciting reading!

Photo: Roger Schuler

Prof. Jan Cosyn (BEL), Dr. Jun-Yu Shi (CHN) and Dr. Hong-Chang Lai (CHN) present the latest scientific data and their personal clinical experience in immediate implant placement. This procedure is experiencing an increase in international significance. On the other hand, it also harbors certain risks, which are mitigated by filling the buccal “gap” with Geistlich Bio-Oss®/ Geistlich Bio-Oss® Collagen and Geistlich Bio-Gide®. Thus patient well-being can be effectively enhanced in the spirit of “prevention by regeneration.”

Mirko Zingg Director International Marketing

3


Issue 1 | 2020

NEWS

6

Investment in the tens of millions: prepared for the future

6

OsteoScience Foundation: Going global

7

Follow us!

8

Taking it slowly

8

New look – quality assured

9

Latest studies on preventive strategies

10 Prevention by Regeneration

Regenerative dentistry includes several corrective measures such as rebuilding of lost bone and tissue volume. How about taking action before tissue loss takes hold? FOCUS

11

“I would fill the gap in any case.” Prof. Dr. Jan Cosyn | Belgium

14

Soft tissue management to prevent complications Prof. Jeong Hye Kim | Korea

16

One surgery – even for more extensive defects Dr. Alfonso Rao | United Kingdom

18

“Periodontists and Orthodontists should together develop protective strategies” Ass. Prof. Dr. Hector Rios | USA

21

Preventing alveolar bone resorption: Possibilities and limitations Drs. Jun-Yu Shi & Hong-Chang Lai | China

4

GEISTLICH NEWS 1-2020


OUTSIDE THE BOX

24

“It is about helping patients before problems occur” Interview with Prof. Kenneth Kornman and Dr. Richard Kao

28

Five questions for five experts

30

Yxoss CBR® – a closer look at bone formation Prof. Claudia Dellavia | Italy

31

New beginning for wound healing? Healing problem in diabetes.

34

36

Out of the palate

Magazine for customers and friends of Geistlich Biomaterials Issue 1/2020, Volume 15 Publisher ©2019 Geistlich Pharma AG Business Unit Biomaterials Bahnhofstr. 40 6110 Wolhusen, Switzerland Tel. +41 41 492 55 55 Fax +41 41 492 56 39 biomaterials@geistlich.ch Editor Dr. Giulia Cerino, Verena Vermeulen Layout Larissa Achermann

Dr. Ulrike Schulze-Späte | Germany

Publication frequency 2 × a year

OSTEOLOGY FOUNDATION

Circulation 20,000 copies in various languages worldwide

«A life-changing experience» INTERVIEW

38 39

IMPRINT

A chat with Susana Noronha Publishing information

GEISTLICH NEWS content is created with the utmost care. The content created by third-parties, however, does not necessarily match the opinion of Geistlich Pharma AG. Geistlich Pharma AG, therefore, neither guarantees the correctness, completeness and topicality of the content provided by third parties nor liability for damages of a material or non-material nature incurred by using third-party information or using erroneous and incomplete third-party information unless there is proven culpable intent or gross negligence on the part of Geistlich Pharma AG.

5


Investment in the tens of millions: prepared for the future Location: Wolhusen, Switzerland

Planning and construction period: October 2016 to May 2019

Clean room operating area: 1'310m2

Photo: Roger Schuler

In order to meet increasing demand, Geistlich Pharma AG has decided to increase its production capacity. On 30 August 2019, in the presence of numerous guests, company and city leaders inaugurated building 888 after a two-year construction period and an investment of tens of millions. "The new production building makes us more flexible and prepares the company for the growing demand," says Paul Note, CEO of Geistlich Pharma.

President of the Board Dr. Andreas Geistlich, Municipal Councillor Rita Brunner-Lipp, Wolhusen, and Project Manager Thomas Waldleben at the inauguration (from left to right)

OsteoScience Foundation: Going global Osteo Science Foundation was founded in 2013 by Dr. Peter Geistlich and Geistlich Pharma to promote the regeneration of hard and soft tissue in Oral and CranioMaxillofacial Surgery in North America.

6

GEISTLICH NEWS 1-2020

From 2020 on, the foundation will be expanding to reach an international audience. The first global initiatives will bring regenerative education programs to like-minded Oral and CranioMaxillofacial organizations worldwide.


FOLLOW US ON OUR GEISTLICH CHANNELS!

Website Each subsidiary maintains its own website, including information about products and treatments plus educational opportunities and the latest news. www.geistlich-pharma.com

Blog Want to dive deep into the world of oral regeneration? Find latest studies, expert interviews and cases on: www.regeneration-expert.com

Social Media Things to know about products, treatments, webinars, events, studies, jobs, best practice and live streaming of congresses – follow us on our social media channels. Geistlich Pharma AG @geistlichpharma @geistlichpharma Geistlich Pharma

BioBrief Here you can find cases, including surgical videos from experienced clinicians. www.geistlich-biobrief.com

Webinar World Tour Geistlich Biomaterials offers free webinars held by recognized experts from all over the world. Watch past webinars or sign up for future webinars. www.geistlich-pharma.com/webinar

Illustration: Geistlich Pharma

Webshop Order your Geistlich products online. (webshop availability may vary from country to country)

NEWS

7


Photos: Geistlich Pharma AG

Mastergraft® (β-TCP Hydroxyapatite composite)

Geistlich Bio-Oss® (xenogenic bone substitute)

> Green: cytoskeleton stained with Actin > Red: osteoclasts marker TRAP Actifuse®® (Hydroxyapatite)

> Light blue: nuclei stained with DAPI

Taking it slowly Being in close contact to a bone substitute can trigger monocytes to differentiate into osteoclasts. Consequently, the biomaterial they grow on gets resorbed. This fluorescence-staining series shows that when growing on Geistlich Bio-Oss®

for two weeks, monocytes barely turn into osteoclasts – although ideal conditions for osteoclast differentiation were provided, e.g., with growth factors. The two synthetic bone substitutes Actifuse® and Mastergraft®, on the oth-

er hand, triggered osteoclast formation. This is in line with the clinical observation that Geistlich Bio-Oss® is degraded very slowly. Therefore, it acts as a scaffold for an extended period and the augmented volume is maintained in the long run.

New look – quality assured Have you seen that something changed? Since the beginning of 2020, each product group in the Geistlich product line has been packaged in its own specially color-coded box, making it easier for you to find the product you need when the boxes are stacked on the shelf. The quality inside has remained the same. Every 15 seconds a Geistlich product is used somewhere around the globe.1

References 1

Data on file. Geistlich Pharma AG.

ONE ICON

for one product

8

GEISTLICH NEWS 1-2020

ONE COLOR

for one product family

BONE SUBSTITUTE MATRIX MEMBRANE COMBI


Can Ridge Preservation prevent sinus lift? This question has been investigated in a prospective randomized clinical trial.1 The authors found that without Ridge Preservation 100 % of patients needed sinus floor elevation (72% transcrestal, 28% lateral window approach). With Ridge Preservation, 43 % of patients received implants without sinus floor elevation, only 7% needed a lateral window approach.

Can widening of keratinized tissue prevent complications?

LATEST STUDIE S

The authors of a systematic review and meta-analysis2 tried to answer this question. They concluded from the literature that surgically creating more keratinized tissue revealed a significant reduction in bleeding on probing (gingival inflammation), probing depth and plaque index, plus higher marginal bone levels.

es

gi e t a r t s e v i t n e v on pre

Can corticotomy-assisted orthodontic therapy (CAOT) plus simultaneous bone augmentation prevent bone dehiscences?

Can soft tissue thickening prevent bone loss?

Illustrations: Geistlich Pharma

This question has been investigated in a prospective clinical trial.3 The authors concluded that thickening of thin tissues with an allogeneic membrane on average "reduces crestal bone loss from 1.81 mm to 0.34 mm after 1-year follow-up.”

A systematic review4 was conducted to answer this question. The authors concluded that “CAOT with [bone grafting] could limit crestal bone remodeling or achieved thicker hard tissue dimensions compared to non [grafted] groups. Those results supported the effectiveness of [Phenotype Modification] Therapy prior or during orthodontic treatment … limiting crestal bone remodeling and reducing dehiscence defects.”

References 1

Cha, JK, et al.: Clin Oral Implants Res. 2019; 30(6): 515-23. (40 consecutive patients, Spontaneous healing vs Ridge Preservation with Geistlich Bio-Oss® Collagen and

2

Thoma DS, et al.: Clin Oral Impl Res 2018; 29(Suppl. 15):32–49. (10 studies included)

Geistlich Bio-Gide® (20 patients each)) 3

Linkevicius T, et al.: Clin Implant Dent Rel Res 2015; 17( 3) : 497-508. (103 patients, 3 groups including patients with 1) naturally thin tissue that had not been thickened, 2)

thin tissue that had been surgically thickened, 3) naturally thick tissue (34 - 35 - 34 patients)). 4

Wang CW, et al.: doi: 10.1002/JPER.19-0037. (8 studies included) NEWS

9


FOCUS

Prevention by Regeneration

10

GEISTLICH NEWS 1-2020

Illustration: Quiant

Regenerative dentistry includes several corrective measures such as rebuilding of lost bone and tissue volume. How about taking action before tissue loss takes hold? Here you will find possible solutions to save patients from invasive treatments and to save surgical time.


Immediate implant placement

“I would fill the gap in any case.” Prof. Dr. Jan Cosyn | Belgium Oral Health Sciences Department of Periodontology and Oral Implantology, Ghent University Interview conducted by Dr. Giulia Cerino

Prof. Jan Cosyn, Ghent University, has a lot of experience in the controversial field of implant placement timing. We asked him to shed some light on the question: Immediate implant placement - when is hard and soft tissue grafting indicated? Immediate implant placement is an appealing treatment for patients. Where do you see the biggest advantages? Prof. Cosyn: The time gain is the biggest advantage. First, from the perspective of the patient, because he or she presents with an urgent problem, and the tooth replacement is performed in one day — the implant and the temporary crown. Second, the practitioner performs only one surgical procedure and one prosthetic procedure. This is really time optimization.

Do you see a global trend towards more and more immediate implant placement? Prof. Cosyn: Yes, the trend is increasing everywhere. More and more practitioners are performing immediate implant placements,

because there is more knowledge about the treatment concept, and clinicians are more aware of the pitfalls. However, this does not mean that the risks of immediate implant placement are fully respected. What worries me most is that the treatment is also expanding into untrained hands.

You have recently published a systematic review showing that immediate implant placement has a higher risk for early implant loss than delayed implant placement.1 What are the reasons? Prof. Cosyn: We did several subgroup analyses on the data, because the entire study was composed of eight different clinical comparative studies. Thanks to the analysis, what has become clear is that the use of post-operative antibiotics has a relevant impact on early implant failure. Not prescribing antibiotics with immediate implants results in a 7% higher risk of failure (Fig. 1).

Is it not a general recommendation to prescribe antibiotics after treatment? Prof. Cosyn: Prescribing antibiotics is not a general recommendation in the context of any implant procedure. This has not been shown, or at least there has been no solid data to confirm it. The number needed to treat is quite high to have

“The use of post-operative antibiotics has a relevant impact on early implant failure.”

a benefit in the context of standard implant placement, but this is not the case when you are dealing with immediate implants. It is not possible to generalize for all procedures, but for type I implant placement the use of antibiotics should be considered, and this result is also in accordance with the systematic review of Lang et al. already published in 2012.2

Do you think that hard and soft tissue in the context of immediate implant placement, e.g., “filling the gap”, could make immediate implant placement more predictable? Prof. Cosyn: I honestly do think so. Ten years ago, there was a debate about the need for socket grafting following immediate implant placement. Now we have three randomized controlled clinical studies,3-5 and the last one by Sanz et al.5 is clearly showing a statistically significant difference in favor of socket grafting versus no grafting. So, for maintaining the integrity of the buccal bone wall, it is imperative to perform grafting. However, we also know that this grafting may not be good enough, as it only reduces buccal bone resorption, it does not eliminate it. Different case series from various research groups show that advanced midfacial recession occurs in about 20% of the cases, which is still too high despite socket grafting and a proper diagnosis. Therefore, the need to compensate opens the indication for soft tissue grafting, in most of the cases.

FOCUS

11


In patients in need of a single implant, will immediate as compared to delayed implant placement result in different implant survival? Immediate implant placement ≤ 24h post-extraction

233/473

Delayed implant placement ≼ 3 months post-extraction

240/473

94.9%

98.9%

Implant survival

Implant survival

+ 7% Risk of failure without antibiotic prescription

FIG. 1: Summary of the systematic review and meta-analysis published by Cosyn et al.1

What are the situations in which you would advise including regenerative treatment as part of the overall treatment? Prof. Cosyn: In the anterior especially. I think there is no longer a single situation where I would leave out socket grafting. Interestingly, for the first time it has been shown by Sanz et al.5 that the additional effect of socket grafting does not depend on the size of the gap. The proportional effect is the same for either large or small gaps. So, the clinical recommendation is to fill the gap in any case.

12

GEISTLICH NEWS 1-2020

And how do you fill the gap? Prof. Cosyn: I add bovine bone mineral and gently push the biomaterial in an apical direction using a fine plugger. Over-compression should always be avoided. (Fig. 2)

When is soft tissue grafting indicated in the context of immediate implant placement? Prof. Cosyn: I would say frequently. But let's start with the worst scenario – situations where there is no buccal bone. If you have this situation around a tooth, we know that root coverage procedures are pre-

dictable, but only if there is at least 1.5 mm of gingival thickness. With an implant case, the thickness must be greater, 2 mm, for the simple reason that there are no inserting supracrestal collagen fibers. There are no data on this, only common sense. Since 2 mm soft tissue thickness is only present in about 10% of the cases, starting with the worst case, this means that, in order to be completely predictable in 90% of cases, soft tissue grafting is necessary.

To fully understand this point: If there is a bone dehiscence, soft tissue augmentation becomes more relevant? Prof. Cosyn: Soft tissue grafting is nearly always indicated for an optimal and stable outcome. It becomes even more important when there is a bone dehiscence, in my opinion.

What is in your opinion the minimum amount of buccal bone needed to predictably perform immediate implant placement? Prof. Cosyn: I only perform immediate implant placement when the buccal bone wall is intact. There are some data supporting the concept with small bone dehiscences, but there are no randomized controlled clinical trials or long-term studies on cases lacking more than 50% of the buccal bone wall. Given current knowledge, I don't believe immediate implant placement can be promoted when dealing with compromised buccal bone walls.

Can there be a need for soft tissue thickening even in the presence of intact buccal bone, if the gingival thickness is less than 2 mm? Prof. Cosyn: I believe there is. In the short term, soft tissue grafting leads to less midfacial recession, as shown in the ran-


FIG. 2: A 58-year-old female patient presented with a broken upper lateral incisor. Because of an

intact buccal bone wall and the presence of bone apical and palatal to the extraction socket, type I placement was planned. B

C

D

Photos: Prof. Dr. Jan Cosyn

A

| A Pre-operative occlusal view of tooth 22 that needs to be replaced with an implant. | B Occlusal

view following tooth extraction and immediate implant placement in a palatal position. Note that the bone gap was filled with deproteinized bovine bone mineral (Geistlich Bio-Oss® particles). | C A thin connective tissue graft from the palate was inserted into the buccal pouch and secured with monofilament suture material. | D Occlusal view two days following surgery upon placement of the provisional crown.

domized controlled clinical trial by the Groningen group.6 What I can tell from a 10-year prospective follow-up on single immediate implants in ideal situations in Ghent, is that the soft tissues are more stable when soft tissue grafting was performed. In my view, it is all about longterm tissue stability. Clearly the current knowledge on that is scarce.

Do new techniques, such as 3D imaging, guided surgery or new implant designs, make immediate implant placement more predictable for less experienced surgeons as well? Prof. Cosyn: They can certainly help. My recommendation is to have a CBCT before tooth extraction or immediate implant placement to make an appropri-

ate diagnosis and to evaluate the risks. It is the only way to visualize the buccal bone wall, its thickness and morphology, and the thickness of the soft tissue, if lip retractors are used. Guided surgery is also important because in type I implant placement, the critical mistake is an implant placed too far buccally. This can happen easily in untrained hands, and no CTG can treat the resulting midfacial recession. So to prevent this possibility, the use of guided surgery is a plus, especially for less experienced surgeons.

Could short and narrow implants circumvent regenerative procedures? Prof. Cosyn: No, I don’t think so. Short implants are difficult to use in an alveolus, because you need proper bone anchor-

age. Usually we use longer implants, 11 to 13 mm implants are quite standard for this treatment approach. It’s more important to use small diameters, 3.5 – 3.6 mm, even in the central incisor position, to stay away from the buccal area. And don’t forget, graft the gap in any case. References 1

Cosyn J, et al.: J Clin Periodontol. 2019;46 Suppl

21:224-241 (Systematic review and meta-analysis). 2 Lang NP, et al.: Clin Oral Implants Res. 2012;23

Suppl 5:39-66 (Clinical study). 3 Sanz M, et al.: Clin Oral Implants Res.

2017;28(8):902-910 (Clinical study). 4 Chen ST, et al.: Clin Oral Implants Res.

2007;18(5):552-62 (Clinical study). 5 Mastrangelo F, et al.: Implant Dent.

2018;27(6):638-645 (Clinical study). 6 Zuiderveld EG, et al.: J Periodontol.

2018;89(8):903-914. (Clinical study).

FOCUS

13


Immediate implant placement

Soft tissue management to prevent complications Prof. Jeong Hye Kim | Korea Department of Periodontics Samsung Medical Center, Seoul

Implant placement in post-extraction sites for single teeth in the esthetic zone is a frequent indication. Immediate implant placement obviously has some benefits, but paying attention to the risks is crucial. Pre-operative clinical and radiographic analysis and assessment of the patient's risk profile are essential to appropriately choose between immediate, early and late implant placement.1 Immediate implant placement is attractive, as it avoids post-extraction healing periods of six months or longer. However, because of high surgical risks and more esthetic demands, immediate implant placement in the esthetic zone is a complex and challenging procedure.

Is immediate implant placement a risky procedure? Immediate implant placement into a fresh extraction socket is considered a complex surgical procedure. Implant bed preparation in the sloping anatomy of the palatal bone structure is difficult due to unstable drilling position and impaired visibility. Also, an unnoticed apical perforation of the facial bone – if an incorrect axis of preparation is used – could represent a

14

GEISTLICH NEWS 1-2020

risk. In addition, a facial malposition of the implant is a common mistake and could lead to a 20-30% risk of a mucosal recession greater than 1 mm, according to several studies.2-6

When is immediate implant placement indicated? Immediate implant placement can be used in the following clinical conditions:7 > A fully intact facial bone wall (thick>1 mm) at the extraction site. > A thick gingival biotype. > No acute infection at the extraction site. > Enough apical and palatal bone volume at the extraction site to allow implant insertion in a correct 3D position with enough primary stability.

What are the risks and benefits? In real clinical situations, ideal immediate placement conditions are seldom encountered in the anterior maxilla, where, according to various CBCT studies, a thick wall phenotype is rarely present.8,9 Also, facial soft tissue thickness is generally thin.10 In addition, the facial bone wall is often not intact, but damaged by pathological processes associated with vertical root fractures and endodontic complications. Immediate implant placement is associated with a higher frequency of mucosal recession of >1 mm, mid-facially (median 26% of sites), when compared with early implant placement.11 When

compared with thick biotypes, sites with thin tissue biotype should be regarded as having a greater risk of marginal tissue recession, particularly if the implants are positioned buccally (85.7% for thin biotype vs. 66.7% for thick biotype).4 What are the benefits? It reduces patient morbidity and the number of surgical interventions. Overall the treatment period can be shortened.

What is the effect of soft tissue management? The primary objective of implant therapy in the esthetic zone is an optimal esthetic treatment outcome with high predictability and low risk of complication.12 The stability of the facial hard and soft tissues is paramount to achieving positive esthetic outcomes in the longterm. Thoma et al. reported the effects of soft tissue augmentation procedures on peri-implant health or disease13, concluding that soft tissue grafting procedures result in more favorable peri-implant health and gain of: > Keratinized mucosa using autologous grafts, with a greater improvement of bleeding indices and higher marginal bone levels, > Mucosal thickness using autologous grafts with significantly less marginal bone loss. At esthetically sensitive sites, facial gingival biotype conversion through subep-


FIG. 1: Immediate implant placement in combination with soft tissue augmentation procedure. B

C

D

E

Photos: Prof. Jeong Hye Kim

A

| A Pre-operative clinical situation. | B CBCT showing thin buccal bone plate, periapical lesion and secondary caries. | C The connective tissue graft was

taken from the right palate and sutured with 6-0 Vicryl. | D Provisional restoration performed 2 months after healing. Gingiva around the upper right lateral incisor appeared thickened. | E Clinical situation after 7.5 years.

ithelial connective tissue grafting procedures at the time of implant placement has been proven to be successful in preserving soft tissue levels by rendering the gingival tissue more resistant to recession. 4,14,15 More stable results were observed when a treatment approach of flapless extraction and implant placement was combined with bone grafting, connective tissue grafting and attachment of an immediate provisional crown.14-16 In addition to a favorable implant success rate and peri-implant tissue response, the facial gingival level around single, immediately placed implants can also be maintained following connective tissue grafting, when proper 3D implant positioning is achieved, and bone is grafted into the implant-socket gap.17

Procedure tips and tricks, outcomes and recommendations The clinical case in Figure 1 shows a 46-year-old female patient referred for replacement of the upper right lateral incisor. The tooth was endodontically treated, but a periapical lesion and secondary caries developed. We extracted the tooth due to non-restorability and placed an immediate implant. 3D assessment using CBCT showed a very thin buccal bone plate, the periapical

lesion and secondary caries. The gingival tissue was also a thin biotype. The plan was to augment the soft tissue before extraction in order to have predictable gingival margin height and tissue thickness. Immediate implant placement was performed after extraction of the upper right lateral incisor, and the gap between the implant and the facial bone wall was filled with Geistlich Bio-Oss® and covered with Geistlich Bio-Gide®. Since the gingival margin of the left upper anterior had receded and did not match the contralateral teeth, a connective tissue graft was performed to improve esthetics. This treatment approach has been successful in the longterm; the gingival margin around the implant and on the contralateral teeth is well maintained without gingival recession, except the left canine, for about seven and a half years.

References 1

Hammerle CH, et al.: Int J Oral maxillofac Implants

2004;19 (suppl):26-28. (Consensus statement) 2 Chen ST, et al.: Clin Oral Implants Res

2007;18(5):552-562. (Clinical study) 3 De Rouck T, et al.: J Clin Periodontol 2008;35(7):649-

657. (Clinical study) 4 Evans CD, Chen ST: Clin Oral Implants Res

2008:19(1):73-80. (Review) 5 Kan JY, et al.: J Oral Maxillofac Implants

2011;26(1):179-187. (Clinical study) 6 Lindeboom JA, et al.: Oral Surg Oral Med Oral

Pathol Oral Radiol Endod 2006;101(6):705-710. (Clinical study) 7 Buser D, et al.: Periodontol 2000, 2017;73(1):84-102

(Review) 8 Braut V, et al.: Int J Periodontics Restorative Dent

2011;31(2):125-31. (Clinical study) 9 Januario AL, et al.: Clin Oral Implants Res

2011;22(10):1168-1171. (Clinical study) 10 Chen ST, Darby I: Clin Oral Implants Res

2017;28(8):931-937. (Clinical study) 11 Chen ST, Buser D: Int J Oral Maxillofac Implants

2014;29 (Suppl):186-215. (Systematic review) 12 Buser D, Chen ST: Chicago: Quintessence Publishing

Co., Inc., 2009:153-194. (Book chapter) 13 Thoma D, et al.: Clinical oral Implants Research

2018;29 (Suppl)15:32-49. (Systematic review and meta-analysis) 14 Chung S, et al.: J Oral Implantol 2011;37(5):559-569.

(Clinical study) 15 Bianchi AE, Sanfilippo F: Clin Oral Implants Res

2004;15(3):269–277. (Clinical study) 16 Kan JY, et al.: J Oral Maxillofac Surg 2009; 67(11

Suppl):40–48. (Clinical study) 17 Tsuda H, et al.: Int J Oral Maxillofac Implants

2011;26(2):427–436. (Clinical study)

15


Soft tissue management for large bone augmentation

One surgery – even for more extensive defects Dr. Alfonso Rao | United Kingdom Private practice, Bristol Delta Dental Academy, Bristol

allowing the conformation of an ideal Soft tissue augmentation The stability of hard and 3 strategies soft tissues plays a pivotal profile with the use of a pontic. Periodontal or peri-implant plastic surrole in oral rehabilitation gery procedures have been successfully The significance of soft tissue success – both functionperformed to restore the shape and diaugmentation mensions of soft and hard alveolar tissues Clinical evidence shows that soft tisally and esthetically. This sue augmentations contribute to more before, during or after implant placement. makes the achievement than 40% of the final soft tissue vol- These procedures include ridge augmenof optimal results more ume at implant sites, 4 result in supe- tation with soft tissue, where autologous challenging and leads to a rior esthetics,5 higher papilla scores6, 7 subepithelial connective tissue grafts are greater consideration of all and less mucosal recession.6-8 In addi- considered the gold standard.10, 11 the contributing factors.1,2 tion, initial gingival tissue thickness at The collapse of the alveolar ridge in an edentulous area in patients who will undergo oral rehabilitation impedes the harmonic relationship between pontic and ridge. To correct this type of defect there are several surgical techniques that aim to achieve soft tissue augmentation,

the crest might be considered important for marginal bone stability around implants. Linkevicius et al. were indeed able to demonstrate that, if tissue thickness is 2 mm or less, crestal bone loss of up to 1.45 mm may occur, despite a supracrestal position of the implant-abutment interface.9

Nevertheless, the use of autologous tissues is associated with disadvantages. Typically the quantity and quality of tissue that can be harvested vary depending on the shape of the palatal vault and the patient’s sex and age,12 along with anatomical factors, such as a thick alveolar process, exostosis, and the palatine

FIG. 1: Soft tissue augmentation procedure using Geistlich Fibro-Gide® in a patient presenting maxillary lateral incisor agenesis. B

C

D

E

| A Pre-operative situation after removal of the old adhesive bridge. | B After elevation of a partial thickness flap, Geistlich Fibro-Gide® is inserted in the

recipient area using a pouch technique. | C Primary closure of the flap with no exposure of the matrix. | D, E Clinical situation 3 months after fixation of the bridge. Restorative work performed by Dr. Richard Field, Technician: Stephen Lusty.

16

GEISTLICH NEWS 1-2020

Photos: Dr. Alfonso Rao

A


The Expert's Recommendations WHY? nerves and blood vessels.14 In addition, because of the harvesting procedure, which leads to a prolonged healing time at the donor site, patients often complain about pain and numbness for several weeks after surgery.14, 15 Therefore, to reduce the morbidity and overcome the disadvantages of autologous grafts, soft tissue substitutes represent a great advantage, particularly because bigger areas can be treated in a single surgery.16-18

Our alternative experience In recent clinical studies comparing a xenogeneic, volume-stable collagen matrix (Geistlich Fibro-Gide®) to autologous connective tissue grafts at implant sites, at one year follow up the matrix showed no significant differences in terms of quality and quantity of the stable, augmented soft tissue. In addition, there was no need for a second surgical site, and patients benefited from a lower pain perception.7,11,19 Similarly, in esthetic sites, Chappuis et al. demonstrated that using the matrix for soft tissue augmentation simultaneously with Guided Bone Regeneration and implant placement is safe and feasible.20

ply do not have the quantity or quality necessary for graft harvest. So, now there is a valuable alternative to the connective tissue graft, making the surgeon’s life easier. References 1

D'Addona A, et al.: Int J Biomater. 2012; 531202.

(Review) 2 Maiorana C, et al.: Case Rep Dent. 2016; 8468763.

(Clinical study) 3 Zuniga Araya ME, et al.: Open Journal of

Stomatology. 2018; 8(6):189-19. (Clinical study) 4 Schneider D et al.: Clin Oral Implants Res. 2011;

WHEN? Geistlich Fibro-Gide® can be used at the time of implant placement, or alternatively it can be placed during implant uncovering. It can also be used for conventional prosthetic rehabilitation.

22(1):28-37. (Clinical study) 5 Thoma DS, et al.: Clin Oral Implants Res. 2018; 29

Suppl 15:32-49. (Systematic review and meta-analysis) 6 Thoma DS, et al.: J Clin Periodontol 2017; 44: 185-

194. (Pre-clinical study) 7 Thoma DS, et al.: J Clin Periodontol 2016;

43(10):874-85. (Clinical study) 8 Moraschini V, et al.: Acta Odontol Scand.

2019;77(6):457-467. (Review) 9 Linkevicius T, et al.: Clin Implant Dent Relat Res.

2015; 17(6):1228-36. (Clinical study) 10 Nascimiento de Melo LG, et al.: Perio. 2006; 3(1)

:49-56. (Clinical study) 11 Zeltner M, et al.: J Clin Periodontol. 2017;

44(4):446-453. (Clinical study) 12 Benninger B, et al.: J Oral Maxillofac Surg. 2012;

70(1):149-53. (Clinical study) 13 Yu SK, et al.: J Clin Periodontol. 2014; 41(9):908-

13. (Clinical study) 14 Zucchelli G, et al.: J Clin Periodontol. 2010;

37(8):728-38. (Clinical study) 15 Cairo F, et al.: J Clin Periodontol. 2012; 39(8):760-

In our practice we have been using Geistlich Fibro-Gide® to treat mild or moderate ridge defects, for which soft tissue augmentation is generally enough to repair the deformity. The aim of the clinical case in Figure 1 was to increase the thickness of the soft tissue at the pontic site. Visibly the matrix was secured in the desired area and helped to achieve a good outcome. Although long-term studies are still required, reduced morbidity, unlimited quantity and standardized quality make Geistlich Fibro-Gide® a good option and open doors for patients who fear autologous graft harvesting procedures or sim-

Thickening of soft tissue is beneficial to improve the esthetics of restorations but even more important for marginal bone stability around implants.

8. (Clinical study) 16 Vignoletti F, et al.: J Clin Periodontol. 2014; 41

Suppl 15:S23-35. (Review) 17 Zuhr O, et al.: J Clin Periodontol. 2014; 41 Suppl

15:S123-42. (Review)

HOW? It is important to trim Geistlich Fibro-Gide® to the desired size to fit into the defect. The device will transiently gain approximately 25% in volume upon wetting, so consider the swelling when determining the final dimensions. The mobilization of a generous flap is key to managing particularly large defects and to assuring full coverage of the matrix. To achieve predictable results, Geistlich Fibro-Gide® should be submerged without exposure. Close to wound margins, reducing the thickness of the matrix by 2-3 mm might be beneficial to avoid dehiscences during the healing phase.

18 Gargallo-Albiol J, et al.: Int J Oral Maxillofac Im-

plants. 2019;34(5):1059–1069. (Systematic review and meta-analysis) 19 Huber S, et al.: J Clin Periodontol. 2018; 45(4):504-

512. (Clinical study) 20 Chappuis V, et al.: Int J Periodontics Restorative

Dent. 2018; 38:575-582. (Clinical study)

WHAT IF? A dehiscence and exposure of the matrix can happen. Nevertheless, in our experience no infections have been detected and no premature removals of the matrix have been necessary. Suturing the device to the underlying soft tissue is advisable to secure the matrix, reducing the risk of dislocation.

17


Orthodontics’ effect on periodontal phenotype

“Periodontists and Orthodontists should together develop protective strategies” Ass. Prof. Dr. Hector Rios | USA Private Practice in Holland, Michigan Department of Periodontics and Oral Medicine School of Dentistry, University of Michigan Interview conducted by Verena Vermeulen

Orthodontic tooth movement can increase the incidence of bony dehiscence and gingival recession. Dr. Hector Rios, USA, investigates how this effect can be minimized. We talked to him about healthy conditions, short treatment time and long-term success.

tooth movement and the local anatomy—these effects can be physiologic, or they can increase the vulnerability of the surrounding tissue.1

Dr. Rios, what is the challenge for the bone when teeth are moved for orthodontic treatment?

Dr. Rios: 20-35 percent of patients develop gingival recessions after orthodontic treatment.1 The incidence of bony dehiscence and gingival recession is higher in teeth surrounded by thin periodontal phenotypes.2 Lower incisors and upper or lower canines are especially prone to soft tissue breakdown. The problems mostly start years after the treatment.1 So, for the patient the cause is not apparent.

Dr. Rios: Orthodontic tooth movement has two different effects on bone. On the compression side, we see a catabolic effect, leading to bone resorption. And on the tension side, new bone is formed, so we see an anabolic effect. Depending on several factors—such as the magnitude of the force, direction of

Does tooth movement influence soft tissue as well? Dr. Rios: Yes. Often, gingival recessions are the more tangible signs for the underlying cause, which is bone loss.

Do problems often occur? If so, which and when?

“20-35 percent of patients develop gingival recessions after orthodontic treatment.”

Surgically accelerated orthodontics is a relatively new treatment option. What does it mean? Dr. Rios: It’s not really a new treatment option, but it is definitely more in demand now. Surgically accelerated orthodontics includes dentoalveolar bone decortication. This accelerates tooth movement in a certain time frame after an injury.3 There are many different treatments that fall under this category. The decortication can, for example, be combined with bone and/or soft tissue augmentation, and it can be done in a minimally-invasive way or with flap elevation.

What is the effect of the decortication? Dr. Rios: On the one hand, it is obviously a mechanical effect. The bone is slightly damaged and a tooth can be moved more easily in this damaged zone. But there is also a biochemical effect. Damaging the cortical layer induces the release of pro-inflammatory cytokines such as interleukin 1-beta or interleukin receptor-antagonist. These molecules cause a transient osteopenia. During this “window of opportunity” tooth movement is accelerated.3

What is the advantage compared to conventional orthodontic treatment? Dr. Rios: Most adult patients undergoing orthodontic treatment want a quick solution. And with this option, treatment time

18

GEISTLICH NEWS 1-2020


FIG. 1: Surgically accelerated orthodontics and Phenotype Modification Therapy.

B

C

D

Illustration: Quiant

A

FIG. 1: | A Pre-operative clinical situation of a patient under orthodontic treatment. | B Vertical and interradicular gingival incisions are performed on

the buccal aspect of the mandibular arch, starting 2-3 mm below the interdental papilla with enough depth to allow the piezotome to reach alveolar bone. | C A tunnel is created, and the collagen matrix is pulled into the tunnel. | D The sutures for the collagen matrix are located in the inter-proximal / interradicular space and engage at least half of the material.

can be reduced significantly, by about 50 percent.4 Patients also report less pain.5 And the combination of dentoalveolar bone decortication and bone augmentation with a bone substitute—known as surgically facilitated orthodontic treatment (SFOT) or periodontally accelerated osteogenic orthodontics (PAOO)—can create additional space for tooth movement and maintain the thickness of the buccal bone after mandibular decompen-

sation. This can be highly beneficial for the overall treatment plan and avoid unnecessary tooth extractions. Finally, surgically accelerated orthodontics should reduce the level of orthodontic relapse.

So, the risk of iatrogenic sequelae is lower compared to non-surgical orthodontic treatment? Dr. Rios: Yes, just recently a Best Evidence Review from the American Acad-

emy of Periodontology concluded that SFOT enhances post-orthodontic stability of the mandibular anterior teeth3. But long-term tissue loss after orthodontic treatment has not yet been fully investigated. What we can say today is that orthodontic treatment in general might add to the susceptibility of the tissue and that understanding both treatments better will make them both safer.

19


“It requires a change of mindset from correcting defects to protecting tissues.”

You did a study on the combination of SFOT and phenotype modification therapy. What did you want to find out? Dr. Rios: The study included 40 patients in need of orthodontic treatment.5 They were divided into four groups. First: control group with conventional orthodontics, second: orthodontics plus piezocision, third: orthodontics plus piezocision plus collagen matrix and fourth: orthodontics plus collagen matrix without piezocision. So, on the one hand, we compared conventional orthodontic treatment with SFOT. On the other hand, we investigated whether combining decortication with a collagen matrix on the periosteum has a positive effect. (Fig. 1)

How so? Dr. Rios: Our idea is that the spongy layer of the collagen matrix serves as a reservoir for the pro-inflammatory cytokines that are produced in the bone because of the corticotomy. Collagen is known to have this capability. By storing the cytokines and releasing them over a longer period, Geistlich Mucograft® may extend the window of opportunity in which tooth movement is facilitated. On the other hand, the denser layer of the

20

GEISTLICH NEWS 1-2020

matrix should protect the buccal perio­ dontium from invasion of soft tissue fibroblasts. This gives fibroblasts from the periodontium the space to become bone forming cells and thereby support new bone formation. It’s beneficial to separate these two tissues for a while so that the new osteoblasts are not suppressed by faster growing soft tissue fibroblasts.

Did you see this effect? Dr. Rios: We could see a positive effect on vestibular bone height and gingival thickness and certainly a positive effect on treatment time.5 The latter was in the collagen matrix group even shorter than in the SFOT group without collagen matrix. We would expect further improvements in buccal bone thickness in the two collagen-matrix groups over time. But we don’t have the results yet.

What does this mean for clinical practice? Do you advise protecting the bone with a collagen matrix in the context of orthodontic treatment? Dr. Rios: Absolutely. And I think it is important that periodontists and orthodontists together develop protective strategies to ensure a healthy periodontal phenotype in the long run. This includes

standard treatment goals to minimize an increase in tissue vulnerability through orthodontic treatment. It also requires a change of mindset from correcting defects to protecting tissues.

References 1

Renkema AM, et al.: Am J Orthod Dentofacial Or-

thop. 2013 Feb;143(2):206-12. (Clinical study) 2 Jepsen S, et al.: J Periodontol. 2018 Jun;89 Suppl

1:S237-S248. (Consensus report) 3 Wang CW, et al.: J Periodontol 2019 Oct 31. [Epub

ahead of print] (Best Evidence Review) 4 Zimmo N, et al.: J Int Acad Periodontol 2018; 20: 153-

62. (Systematic Review and Meta-Analysis) 5 Unpublished data


Ridge Preservation

Preventing alveolar bone resorption: Possibilities and limitations Drs. Jun-Yu Shi & Hong-Chang Lai | China Department of Oral Implantology Shanghai Ninth People’s Hospital Shanghai JiaoTong University

Osseointegration is no longer the only criteria for implant success. Sufficient peri-implant bone volume also plays a decisive role in maintaining long-term stability and esthetics. Thus, prevention of alveolar bone resorption has become a lively topic. Spontaneous socket healing vs. immediate implant placement

FIG. 1: A case for flapless immediate implant placement: stable mid-facial mucosal level, buccal

bone plate resorption 21%. A

D

E

B

F

G

C

H

I

The protocol for placing implants immediately in fresh sockets was introduced in 1978.2 Several studies have demonstrated that the timing of implant placement does not influence socket remodeling. Similar alveolar width reduction (up to 56%) was reported following immediate implant placement (IIP).3,4 In these studies, all implants were placed in the center of the socket without any bone grafting procedures. In other words, IIP alone does not interfere with sequential socket healing but also does not prevent ridge resorption.

Photos: Drs. Jun-Yu Shi & Hong-Chang Lai

Alveolar ridge dimensional changes following spontaneous socket healing have been investigated in a series of clinical studies. In the first year following tooth extraction, alveolar ridge resorption results in 2.6-4.5 mm loss of width (about 50%) and 0.4-3.9 mm loss of height.1

| A Before surgery. | B At crown delivery. | C 1-year examination. Radiographic assessment.

| D Before surgery. | E At crown delivery. | F 1-year examination. | G Before surgery. | H Immediately after surgery. | I 1-year examination.

21


Alveolar ridge preservation vs. immediate implant placement with gap grafting

Illustration: Quaint/Geistlich Pharma AG, based on Avila-Ortiz et al.6

Alveolar ridge preservation (ARP) is one of the best documented technologies for preventing alveolar bone resorption and compensating for socket remodeling.5 A recent meta-analysis reported that ARP, as compared to spontaneous socket healing, can prevent 1.99 mm horizontal, 1.72 mm vertical mid-buccal, and 1.16 mm vertical mid-lingual bone resorption.6 Another study has demonstrated that ARP can prevent about 15-25% horizontal bone resorption compared with spontaneous socket healing and allows implant placement into the prosthetically driven position without further bone augmentation procedures in 90.1% of the ARP sites but only 79.2% of the control sites.7

22

GEISTLICH NEWS 1-2020

We have already demonstrated that IIP alone can’t prevent resorption of the alveolar ridge; however, results can be totally different when guided bone regeneration (GBR) procedures are used. A previous prospective study reported that Geistlich Bio-Oss® can significantly reduce horizontal resorption of buccal bone following IIP (Geistlich Bio-Oss ® group: 15.8±16.9% resorption, Geistlich Bio-Oss ® + Geistlich Bio-Gide® group: 20.0±16.9% resorption, control group: 48.3±9.5% resorption).4 A recent review also concluded that the original shape of the ridge can be maintained by placing implants palatally and filling gaps with grafting materials.8 In our center IIP is a routine treatment option for replacement of single teeth in the anterior region with

limited buccal bone dehiscences (less than 20%). The resorption rate of buccal bone ranges from 18% to 25%, and advanced recession of mid-facial mucosal is rare (<5%). (Fig.1) The resorption rate of buccal bone (1520%) following IIP combined with GBR is similar to ARP. Theoretically, healing processes of ARP and IIP combined with GBR are similar, since the implant itself will not interfere with socket remodeling. So it makes sense that IIP combined with GBR procedures can achieve similar outcomes preventing alveolar bone resorption, as long as implants are placed in an optimal 3D position, which is a challenging surgical procedure. It will be interesting to examine in experimental animal models whether sockets with ARP and


“Compared with early implant placement, several studies have concluded that IIP increases esthetic risk.� IIP combined with GBR show any differences in sequential healing .

Limitations for immediate implant placement It must be noted that, compared with early implant placement, several studies have concluded that IIP increases es-

thetic risk.9,10 Although some clinicians advocate a flapless procedure, palatally-positioned implants, narrow-diameter implants, gap filling with grafting materials, augmentation of soft tissue at implant surgery and socket shield procedures when implants are placed in fresh sockets,11 excellent esthetic outcomes can only be achieved in strictly-selected cases.12 Another important concern is the slightly higher early implant failure for IIP compared with delayed implant placement (5.1% vs. 1.1%),13 especially when prophylactic antibiotics are not used. In conclusion, compared with spontaneous socket healing, both alveolar ridge preservation and immediate implant placement combined with guided

bone regeneration procedures can reduce alveolar ridge resorption rates (1525%). However, strict indications and a potentially higher early failure rate must be taken into consideration before making clinical decisions. References 1

Van der Weijden F, et al.: J Clin Periodontol

2009;36(12):1048-58. (Systematic review) 2

Schulte W, et al.: Dtsch Zahnarztl Z 1978;33(5):348-

3

Botticelli D, et al.: J Clin Periodontol

4

Chen ST, et al.: Clin Oral Implants Res

5

Jung RE, et al.: Periodontol 2000 2018;77(1):165-175.

6

Avila-Ortiz G, et al.: J Clin Periodontol 2019;46 Suppl

59. (Clinical study) 2004;31(10):820-8. (Clinical study) 2007;18(5):552-62. (Clinical study) (Review) 21:195-223. (Systematic review and meta-analysis) 7

Willenbacher M, et al.: Clin Implant Dent Relat Res

2016;18(6):1248-1268. (Meta-analysis) 8

Clementini M, et al.: J Clin Periodontol

2015;42(7):666-77. (Systematic review and meta-analysis) 9

Araujo MG, et al.: Periodontol 2000 2019;79(1):168-

177. (Review)

Ridge Preservation prevents:

10 Buser D, et al.: Periodontol 2000 2017;73(1):84-102.

(Review) 11 Kan JYK, et al.: Periodontol 2000 2018;77(1):197-212.

(Review) 12 Vignoletti F, Sanz M: Periodontol 2000

mm mm horizontal bone resorption

2014;66(1):132-52. (Review) 13 Cosyn J, et al.: J Clin Periodontol 2019;46 Suppl

21:224-241. (Systematic review and meta-analysis)

mm vertical mid-lingual bone resorption

mm mm vertical mid-buccal bone resorption

23


Phenotype Modification Therapy

“It is about helping patients before problems occur” Interview with Prof. Kenneth Kornman and Dr. Richard Kao conducted by Verena Vermeulen

In August 2019 the American Academy of Periodontology (AAP) organized a Best Evidence Consensus (BEC) about Phenotype Modification Therapy. What were its findings? We discussed with Prof. Kenneth Kornman and AAP president Dr. Richard Kao. Phenotype Modification Therapy (PhMT) was the overall topic of the Best Evidence Consensus 2019. What does the term “phenotype” mean?

And “phenotype modification” then means to change a thin phenotype into a thicker one? Dr. Kao: Yes. Because in case of implant placement or orthodontic treatment, patients with a thin phenotype, for example thin buccal bone or thin soft tissues, are more prone to developing gingival recessions. These patients will benefit if we change the conditions and modify their phenotype to achieve sustainable results.

Prof. Kornman: I agree. Phenotype Modification Therapy is about recognizing patients’ individual situations and helping them before problems occur. We see this as an important area to focus on for the future. The starting point for the BEC is to determine where there is a true clinical need. If there is a need, how are clinicians managing those needs today? The BEC process produces summaries of evidence and clinical experiences that are currently available to help increase confidence in certain specific clinical applications. We are certainly broadening the ability of our clinicians to help more patients live well longer.

You discussed several indications, where PhMT could benefit patients. Which indications were these? Dr. Kao: We focused on the tissues around teeth1, around implants2, in the context of

Photos: Daniele Micieli

Dr. Kao: Phenotype means what you see, but it’s also based on genetic fac-

tors. Asians for example have shorter roots and a different crown-to-root ratio. Their tissues are overall thinner compared to Caucasians, and they have more bone dehiscenses. They have different phenotypes. Minor gum disease, bone loss or attachment loss may have a greater impact in these patients.

Discussing with Dr. Richard Kao (left) and Prof. Kenneth Kornman at the AAP’s 2019 Annual Meeting in Chicago.

24

GEISTLICH NEWS 1-2020


orthodontic treatment3. The main questions were: When is it beneficial to thicken soft tissues, to create more keratinized tissue or to thicken the bone? For example, in the context of implant placement: Is there a benefit in thickening the soft tissue in addition to augmenting the bone?

One reason could be that the peri-implant mucosa is more vulnerable than the gingiva around a tooth. Is this the case? Dr. Kao: Yes, the tissues around an implant are more susceptible to tissue damage or tissue loss than around teeth. There are no Sharpey’s fibers and cementum. The connective tissue contains fewer blood vessels and fibroblasts. Literature shows that the bony housing in the front area is very thin in most patients.1 With time and age, this is one of the most predictable areas for gum recession, even around teeth. With an implant the risk is even higher, independent of how well an implant has been placed. So, there are good reasons to better prepare the ridge before placing an implant.

What did the consensus group conclude with regards to soft tissue around implants? Dr. Kao: Dr. Guo-Hao Lin and colleagues prepared a meta-analysis on the significance of surgically modifying soft tissue phenotype around fixed dental prostheses. One of the conclusions was that increasing soft tissue thickness and the amount of keratinized tissue may be beneficial for providing more favorable peri-implant tissue health.1 And in the consensus statement it is stated that phenotype modification

Bridging the gap between evidence and opinion Prof. Kornman explains the main idea behind the Best Evidence Consensus concept.

Prof. Kornman, you are called the inventor of the Best Evidence Consensus format. How did the idea start? Prof. Kornman: For several years, the Journal of Periodontology has been receiving large numbers of well-constructed systematic reviews on valuable clinical topics. But given the limited evidence that is often available, the authors rarely concluded with what would be useful for clinicians to incorporate into specific types of cases now.

They typically end with “further research is needed.� Prof. Kornman: Exactly. So, at some point, we stopped considering for publication systematic reviews that were initiated by the authors themselves. We spent years discussing how we could provide perspective on clinical application of certain technologies that lots of people are using, although there may not be as much published data as we would like. This is when the idea for the Best Evidence Consensus started.

In the consensus meeting, the existing evidence is combined with the clinical expertise of the consensus group. How does this combination work? Prof. Kornman: We came up with a very formal and effective process to fill the gap between evidence and opinion. An important factor is that we are always very clear on what the sub-questions are to the primary questions. Then we commission extensive systematic reviews on the sub-questions, and that exercise often provides more knowledge that moves us closer to broader clinical applications than many were aware. During the meeting itself, the results are discussed by knowledgeable clinicians who have used the technology, have opinions about it and can talk about their experience. We want to know where they see specific opportunities and weaknesses and how that fits with the existing evidence. The results of these intense discussions are put together in a consensus report that allows us to communicate with interested clinicians around the world.

OUTSIDE THE BOX

25


therapy around fixed dental prostheses can improve esthetics—e.g., create a more harmonious soft tissue architecture and decrease show-through of restorations, abutments and implants—and that it also improves comfort, hygiene and maintenance.4

The third topic was phenotype modification in the context of orthodontics. Why is there a need to modify? Dr. Kao: Literature shows that 20-35% of patients develop facial gingival recession two to five years after orthodontic treatment.3 This is dependent on the phenotype, but also on the cranial and facial arrangement. If bone and soft tissue are thin, recessions will develop very soon after orthodontic treatment. If the bone is thin, but the tissue is thick, recessions will be visible only years later.

How is phenotype modification done in this context? Which method was discussed in the systematic review and during the meeting? Dr. Kao: For most orthodontic treatments, there is usually adequate volume of bone and soft tissue. Where there are concerns for gingival recession, clinicians can proactively “thicken” the gingiva with grafting procedures. When the orthodontic treatment planning and analysis indicate the

Dr. Kao and two of his colleagues have together treated 1,500 patients with an SFOT approach. “The three of us came out with the same strategy for about 90 percent of the treatment. On the other 10% we disagreed.”

required orthodontic movements would be beyond the bony and soft tissue envelop, surgically facilitated orthodontic therapy, SFOT, periodontally accelerated osteogenic orthodontics, PAOO, and corticotomy-assisted orthodontic therapy, CAOT , are the most common procedures. They involve corticotomy surgery and decortication of the dentoalveolar complex with or without particulate bone grafting. The goal is to enable faster tooth movement and widen the jaw bone. Chin-Wei Wang et al. focused on these techniques in their meta-analysis on the question: Is periodontal phenotypic modification

therapy beneficial for patients receiving orthodontic treatment?3

What do they conclude from the literature? Dr. Kao: Treatments such as SFOT, PAOO and CAOT may shorten treatment time and accelerate tooth movement. But they also supported an increased scope of tooth movement. They achieved thicker hard tissue dimensions and reduced dehiscence defects. And finally, they enhanced post-orthodontic stability of the mandibular anterior teeth—a typical area with very thin bony envelops—and had a potential

Definition box Phenotype is the appearance of an organ based on genetic traits and environmental factors. With regards to the oral cavity, the phenotype includes, for example, bone thickness and soft tissue quality and thickness.

26

GEISTLICH NEWS 1-2020

Phenotype Modification Therapy refers to surgical intervention involving soft and/or hard tissue augmentation/modification to convert phenotype from thin to thick in both natural dentition and dental implants (or from thick to even thicker).


Illustration: Quiant

FIG. 1: These three topics were discussed at the AAP Best Evidence Consensus 2019.

Does the modification of gingiva

What is the effect of surgically modifying

Is periodontal phenotype modification

from a thin to a thick phenotype maintain

soft tissue phenotype around fixed

therapy beneficial for patients receiving

periodontal health?

dental prosthesis?

orthodontic treatment?

to reduce the level of orthodontic relapse over a 10-year follow-up period.4

tion Therapy should be pursued prior to orthodontic treatment in patients with thin phenotype when the necessary orthodontic tooth movement would compromise the bony housing.4 And there will be situations in which both bone and soft tissue augmentation are necessary.

ing a paper on how this interdisciplinary work between orthodontists, periodontists and possibly also oral surgeons can be organized most efficiently.

Few studies have been published in this field so far. What was the experience in the consensus group? Dr. Kao: Three of us have treated a total of 1,500 cases with these techniques. So, we shared our documentation and notes. What are the materials we used? What was the sequence of events? What were the watch-out points, the diagnostic tools we needed? What have we tried that did not work? In about 90 percent of content the three of us came up with the same strategy. On the other 10% we disagreed. But that’s okay. It shows us where there is some clinical flexibility.

Did the consensus group conclude that PhMT is beneficial in the context of orthodontic treatment? Dr. Kao: Yes, the consensus group concluded that Phenotype Modifica-

Are orthodontists aware of these developments? Dr. Kao: Yes, orthodontists nowadays have computer modelling systems based on CBCT data, where they plan how much they are going to move the teeth and what this will mean for the bony housing. So, we can together plan how to protect the envelope and prevent longterm complications with an interceptive thickening of the gum and bone.4

Is this interdisciplinary work also a source of error? Dr. Kao: Collaboration is certainly beneficial and the way to go for the future. Dr. George Mandelaris is currently prepar-

Is there also a broader collaboration planned between periodontal and orthodontic societies? Dr. Kao: The AAP and the American Orthodontic Association are both very interested in collaboration. We have a joint conference set for 2021, and we are currently thinking about teaming up for an e-learning platform. This will definitely help to disseminate this kind of information to a broader population.

References 1

Kim DM, et al.: J Periodontol 2019 Nov 6. [Epub

ahead of print] (Review) 2 Lin GH, et al.: J Periodontol 2019 Oct 31. [Epub

ahead of print] (Review) 3 Wang CW, et al.: J Periodontol 2019 Oct 31. [Epub

ahead of print]. (Review) 4 Kao, R. et al.: J Periodontol 2020 Jan 13. [Epub

ahead of print]. (Consensus)

OUTSIDE THE BOX

27


Points of view

Five questions for ďŹ ve experts We asked five research, award winning clinicians to answer five questions about research. Results: 25 professional and personal insights. And a generation comparison!

Prof. Giovan Paolo Pini Prato | Italy

Gabriel Leonardo Magrin | Brazil

University of Florence

Medical University of Vienna – Federal University of Santa Catarina

What research award makes you the proudest?

What research award makes you the proudest?

The EFP Distinguished Scientist Award 2019. It is a recognition of my long career as a researcher and clinical practitioner.

The 2019 European Prize for Basic Research in Implant Dentistry from the EAO.

What do you think was the winning factor? The meticulous gathering of all short- and long-term data. They are essential!

What advice would you give to those who start doing research? When planning a clinical or basic research project, ask yourself just one question, and answer with a precise protocol.

28

GEISTLICH NEWS 1-2020

What do you think was the winning factor? The collaboration between the research groups in Austria and Brazil. The mentorship I had in Vienna and the motivation of being involved in an innovative study led to the goal.

What advice would you give to those who start doing research? I think that being proactive and working in synergy with colleagues are good starting points!

Have you ever stopped a research project?

Have you ever stopped a research project?

I recall just two projects that could not be conducted due to high costs and difficulties in finding financial support.

So far only projects in the concept phase. I'm learning that planning activities and sharing responsibilities help manage the workload.

How much time do you spend doing research vs. treating patients?

How much time do you spend doing research vs. treating patients?

I believe more time should be devoted to research. In my case, the ratio is 4:2.

I am enrolled in a full-time PhD program involving both basic and clinical research. So, I would say 50:50.


Dr. Jennifer Chang | USA

Simone Cortellini | Italy

Prof. Ki-Tae Koo | Korea

University of Texas

Catholic University of Leuven

Seoul National University

What research award makes you the proudest?

What research award makes you the proudest?

What research award makes you the proudest?

The first prize in Clinical Research for the 2018 National Osteology Symposium USA.

The 2018 European Prize for Clinical Innovations in Implant Dentistry from the EAO.

The first prize in Clinical Research at the 2019 International Osteology Symposium.

What do you think was the winning factor?

What do you think was the winning factor?

What do you think was the winning factor?

Probably the fact that our results can help clinicians better understand how PRF enhances tissue regeneration.

The award is based on both the project and the quality of the presentation. It was a RCT comparing L-PRF block vs xenograft alone in lateral sinus lift procedure. As for the quality, I admit that having a good teacher at home helps! (Pierpaolo Cortellini).

The depth and quality of the data. Also, I think the topic and the fact it was an RCT helped a lot.

What advice would you give to those who start doing research? Find a topic you love and the people with whom you are comfortable working. Then the entire research process can be very enjoyable.

Have you ever stopped a research project? Not yet! And I have a positive attitude... If you don’t give up, the result can be even better than you could imagine.

How much time do you spend doing research vs. treating patients? At school I spend half of my time treating patients. The rest is dedicated to research.

What advice would you give to those who start doing research? Don't do research alone; a well performed research is the result of a team effort. And if you do research, do it at the top level to improve your scientific and clinical knowledge!

Have you ever stopped a research project?

What advice would you give to those who start doing research? Be patient and enjoy. Also, allow time to get to the expert level.

Have you ever stopped a research project? Not really! I have been taught to accept biology objectively. Even if your data are not aligned with your goals, you can still achieve meaningful results.

Not yet, but it is true that I am still young and there will be time!

How much time do you spend doing research vs. treating patients?

How much time do you spend doing research vs. treating patients?

Being honest, I do receive a good salary from the University, so I have to contribute accordingly. I would say 40:60.

I work full-time in academia, doing my PhD. I would roughly say 40:60.

OUTSIDE THE BOX

29


Histology

Yxoss CBR® – a closer look at bone formation Prof. Claudia Dellavia | Italy Department of Biomedical, Surgical and Dental Sciences University of Milan

A

C

D

E

Photos: Claudia Dellavia

B

FIG. 1: Toluidine Blue and Pyronin Yellow staining of one representative sample. Osteoid and cells (blue), tissue in phase of mineralization (purple), Geistlich Bio-Oss® and highly mineralized bone (brown). | A Overview. | B-C 200X. | D-E 400X.

A 50:50 mix of autologous bone and Geistlich Bio-Oss® granules was grafted on human atrophic alveolar crests, stabilized with Yxoss CBR®, fixed with titanium micro-screws and covered with Geistlich Bio-Gide®. After nine months, histological anal-

30

GEISTLICH NEWS 1-2020

ysis showed highly mineralized and well-organized new bone (A) with dense osteoid matrix, mainly located in the coronal portion (B). Geistlich Bio-Oss® remnants were perfectly osseointegrated and surrounded by marrow spaces populated by numerous

blood vessels without inflammatory infiltrates (C). Many fronts of bone remodelling rich in osteoblasts depositing new matrix (D) and osteoclasts in a resorption lacuna (E) confirmed the vitality of the regenerated bone.


New beginning for wound healing? Healing problem in diabetes

OUTSIDE THE BOX

31


Dr. Klaus Duffner

Approximately one in three diabetes patients develops a foot wound over the course of his life.1 Why doesn't tissue regeneration work anymore in such cases? And can better understanding bring about new therapies? Natural healing of a wound is a highly complex and at the same time well-organized biological process. It operates in four phases: hemostasis, inflammation, proliferation and remodeling.

From emergency care to regeneration Following an injury, thrombocytes are activated unleashing the coagulation cascade in the area of the bleeding wound. Both form part of primary “emergency care”, i.e., bleeding must be stopped. From this first step there very swiftly follows an inflammatory phase in which neutrophil granulocytes, macrophages and T-lymphocytes are sent to the wound on the very first day. They are tasked with removing bacteria and damaged tissue.2,3 This inflammation reaction is fueled by various cytokines. It moves seamlessly into the subsequent proliferative phase in which new tissue, new blood vessels and a new extracellular matrix fill up the wound area. In this phase various growth factors and cytokines are released to support the process of rebuilding. Under the influence of epidermal or keratinocyte growth factors the migration of fibroblasts and construction of an extracellular matrix are promoted.3 Matrix metalloproteinases (MMP) are also integrated into different stages of wound healing. They stimulate cell migration and the restoration of the

32

GEISTLICH NEWS 1-2020

epithelium. Towards the end of the healing process there is an influx of keratinocytes from the edges of the wound. The strong circulation of blood decreases, and a new epithelium forms.

sites.3 Lastly, stem cells, which after an injury normally differentiate into different cells in the epidermis also exhibit functional disorders, especially in the wounds of the elderly.

The core problem – Inflammation

Bacteria create their own environment

“These processes are extremely complex, as a great many factors also play a part,” says Prof. Dr. David Armstrong of the University of Southern California/Los Angeles.4 At least as complex are events revolving around chronic diabetic wounds, in which the described natural wound healing processes are disrupted. “This is like a sluggish computer in which various programs are active in the background,” says the wound expert. “We have immune cells, inflammatory cytokines, chemo­ kines, cell-cell interactions, none of which continue to be under control. They prevent the normal process of wound healing.”5 In fact, neutrophils, macrophages and T-cells are over-activated and the quantity of proinflammatory cytokines and tissue-reducing proteases remains permanently elevated.3 Fibroblasts and endothelial cells do not multiply - and so the last phase of wound healing simply ceases to be. The wound remains open.

As if that were not enough, over half of diabetic wounds are infected with bacteria.6 In western countries these are chiefly aerobic gram-positive bacteria such as Staphylococcus and Streptococcus.4 “Bacteria are interested in a wound remaining open. They create their own milieu, produce a biofilm and develop barriers which are meant to prevent jeopardy to this environment, i.e., an improvement in the wound,” says David Armstrong. The biofilm consisting of polymeric sugar, proteins, and bacterial DNA protects the microbes from endogenous cells.3 If the condition of the wound worsens over time, the bacterial flora also becomes more complex and more diverse. Furthermore, fungi often populate this environment too.

Aggressive M1 macrophages play a role An imbalance of activated M1 macrophages and M2 macrophages plays a key role, notes Armstrong.4 Whereas inflammation-promoting M1 macrophages are normally replaced by the “gentler” M2 macrophages at some point, the level of the aggressive M1 macrophages remains high in chronic wounds. “They then function as permanent fire accelerants,” says the American expert. High levels of reactive oxygen species and the increase in free iron also characterize such open

Supporting the healing process People have long been trying to promote the healing of chronic wounds through a wide range of different measures. Thanks to fundamentally new scientific findings on the molecular and cellular formation process of wounds, it has been possible to develop new treatment strategies in the last few years. Thus, attempts are being made to stimulate the production of substances and cells which promote healing by using growth factors. Gene therapy approaches are also being researched. In negative pressure wound therapy a vacuum is applied to the wound, which promotes blood vessel formation and in turn boosts the oxygen and nutrient


425

Illustration: Geistlich Pharma, based on diabeticfootonline.com

MILLION diabetics worldwide

8

(50% of them are not aware)

MILLION inhabitants with chronic wounds

20% of these wounds end in amputation

80% of amputations not caused by accidents are due to diabetes

200% RISK

50% 30%

The risk of dying is double for diabetics with wounds.

of them have bacterial infections

of diabetics worldwide develop foot wounds

FIG. 1: Diabetes is frequent and can have severe consequences.

supply in the wound area, which can be very beneficial for wound healing.

Geistlich conducts research in this area Geistlich developed a purified reconstituted bilayer matrix which shows very promising effects in the healing of chronic wounds.7 The upper compact layer mimics the basement membrane and supports migration of keratinocytes. It provides for the binding of growth factors and mechanical protection of the wound. It also allows suturing of the matrix to the wound if addi-

tional fixation of the matrix is desired by the healthcare professional. The lower porous layer modulates the activity of metalloproteinases and provides an optimum structure for migration of cells. It also absorbs wound fluid readily. In a study in patients whose wounds were an average 3.3 square centimeters in size, the median time until wound closure was 2.7 weeks with this advanced wound matrix.7 “Geistlich Derma-Gide® provides a scaffold for a ‘friendlier’ environment,” notes Armstrong. “This enables a new beginning for healing.”

References 1

diabeticfootonline.com

2

Patel S, et al.: Biomedicine & Pharmacotherapy

3

Matrankonaki E, et al.: JDDG 2016.

4

Prof. Dr. David Armstrong (interview)

Volume 112, April 2019

5

Armstrong DG, Gurtner, GC: Nat Rev Endocrinol

2018; 14(9): 511-12. 6

diabeticfootonline.com

7

Brochure: Geistlich Derma-Gide®, Advanced

Wound Matrix

OUTSIDE THE BOX

33


34

GEISTLICH NEWS 1-2020

© Studio Nippoldt, Berlin


References: see page 39 OUTSIDE THE BOX

35


Focus on Ausra Ramanauskaite

«A life-changing experience» Basil Gürber | Osteology Foundation

If one looks at Ausra Ramanauskaite's professional career over the past five years, one can see that the Osteology Foundation has always been her loyal companion. At the EAO Congress 2019 in Lisbon she reflects on the last years. Balancing a cup of hot coffee in her hand, Ausra Ramanauskaite passes through the vestibule of the«Centro de Congressos de Lisboa». The EAO Congress is in full swing. The first break of the day attracts visitors from all over the world to the bright vestibule, where the many conversations blend to a monotonous buzz. «At this event, nine years ago in Copenhagen, I discovered the Osteology Foundation for the first time», she says and smiles. This is where she met Kristian Tersar, the Foundation's current Executive Director, on the Osteology Foundation stand. He ultimately encouraged her to attend an Osteology Research Academy course.

The journey begins

Research, progress and friends Looking back, Ramanauskaite says, the months in Düsseldorf passed in a flash. She was given the opportunity to participate in various research projects. She investigates the effects of prior bone grafts on the efficacy of peri-implantitis therapy. Despite all these exciting projects, she says, it was the human contacts that made the academic year a completely new experience for her. Working together in an international group of like-minded people opened up new horizons for her. She was able to present her projects at various events and exchange information with other experts in the field. In retrospect «This year had a pronounced influence on my development as a researcher and also my personal development», says Ramanauskaite.

Photos: Osteology Foundation, Ausra Ramanauskaite

And she tells how it all started. On Monday, 15 September 2014, she boards the plane to Zurich in Vilnius. She then took the train to the heart of Switzerland, where the Research Academy course of the Osteology Foundation is held every year in Lucerne. During the next days she acquired the basic tools for her future research activities in lectures, workshops and discussions with experts in the field of oral tissue regeneration. Her personal highlight? «Definitely the career seminar with Niklaus Lang. He shared his wealth of experience from his long research career with us. That was very inspiring», remembers Ausra.

During this course in Lucerne she also learned about the Osteology Research Scholarships for the first time. She can't get the prospect of an environment in which she can deepen her expertise in clinical research and basic research together with a mentor out of her head. Back home in Kaunas, she immediately starts on her application. At that time she is engaged in research on a gel for the treatment of peri-implant tissue infections at the Lithuanian University of Health Sciences. Therefore, she would like to complete her research year in Düsseldorf at the Centre for Oral Medicine and Peri-implant Infections under the chairmanship of Frank Schwarz - particularly as the Heinrich Heine University is the leading institution for research into peri-implant pathology at the time. She logs on to the global Osteology Community Platform, THE BOX, fills in the application form and clicks on "submit application".

36

GEISTLICH NEWS 1-2020


Peri-implantitis remains her passion Today, Ausra is still doing research with Frank Schwarz - but meanwhile at the Goethe University in Frankfurt. She has received an Osteology Researcher Grant for her research project that investigates the influence of antiresorptive therapy on the treatment of peri-implantitis. In addition, she was elected to the Expert Council of the Osteology Foundation in early 2019 and will thus be able to help shape future projects of the Foundation. «I would like to encourage enthusiastic people in our field to take advantage of the support provided by the Osteology Foundation. The Foundation has influenced me a lot on my way and has supported my career», she says looking over the «Ponte de 25 Abril» in Lisbon. She says goodbye and returns to the hustle and bustle of Congress. She is about to moderate the session "How to treat peri-implantitis" together with Frank Schwarz.

Osteology Research Scholarships 2015 – 2019

Facts and Figures 21 Research Scholars from 15 countries 10 Scholarship Centres 9 Mentors 735’000 CHF granted

Meet Miha Pirc – Osteology Research Scholar Would you like to get some insights into the everyday life as an Osteology Research Scholar? On the social media channels of the Osteology Foundation you can now find a video that brings you closer to the tasks and experiences of Miha Pirc at the University of Zurich. @osteologyfoundation @osteologyfoundation Osteology Foundation @OsteologyORG

Publisher ©2020 Osteology Foundation Landenbergstrasse 35 6002 Lucerne Switzerland Phone +41 41 368 44 44 info@osteology.org www.osteology.org

OSTEOLOGY FOUNDATION

37


Interview

A chat with Susana Noronha Interview conducted by Verena Vermeulen

You were co-chair of the EAO congress 2019 – in preparing for that event, what was the biggest challenge? Dr. Noronha: (laughs) My biggest challenge was, undoubtedly, to keep up with the extraordinary dynamism of my dearest friend Gil Alcoforado, the Chairman of EAO Lisbon 2019! Of course, promotion of the scientific program amongst the Portuguese dentists was also demanding. “Bridge to the future” was the congress motto. Will future dentistry be very different? Very digital, for example? Dr. Noronha: The theme “bridge to the future” reflects a strong belief that implant dentistry is undergoing a transitional period. I hope future dentistry will help us understand themes that are not yet fully clear but are present in our daily clinics, for example, why some treatments work well in some situations but not in others. Where do you see the biggest room for improvement? Dr. Noronha: As a periodontist, I think there is still a long way to go in relation to the biological complications around dental implants. It is necessary to improve treatment strategies and find alternatives. Such as: save more teeth? Dr. Noronha: Absolutely! Nobody would think of removing a finger because it has problems, or an ear. With teeth we are too

quick thinking how to replace them. If you can keep teeth longer it’s always better. Even if you just postpone implant placement for some years.

And which of today’s practices are “really worth staying the same” for the years to come? Dr. Noronha: In my daily practice it`s important to maintain a strong focus on prevention. I believe that’s the best way to detect changes early and implement appropriate measures to control known etiological factors of periodontal and peri-implant diseases. The focus of this Geistlich News issue is “preventive measures” – which include all regenerative measures that are not conducted to correct defects but rather to prevent tissue loss or prevent complications. Could this be the regenerative treatment of the future – smart preventive measures instead of major corrections of defects? Dr. Noronha: I hope so. Measures and materials that help us prevent volume loss or avoid complications after implant placement are undoubtedly good options. “Prevention” is the key word! Final question. What do you like to do in your free time? Dr. Noronha: Spending time with my family! And I love reading. I try to read every day; however, it`s not always possible.

Dr. Susana Noronha studied Dentistry at the Instituto de Ciências de Saúde Sul and finished her master’s degree and PhD in Periodontology and Photo: Luís Gomes

Implants at the Complutense University of Madrid.

38

GEISTLICH NEWS 1-2020

She is assistant professor of Periodontology and vice-coordinator of the Master's Degree in Periodontology at the University of Lisbon. She is President of the Portuguese company of Periodontology and Implants (SPPI).


Issue 2 | 20 will be published in July / August 2020. FOCUS

Prevent tooth loss > Saving "hopeless teeth": long-term outcomes > Guided Tissue Regeneration: concepts and indications > Guided Tissue Regeneration: minimally invasive approaches > Latest evidence from scientific literature

References for page 34-35 1

Zadeh HH. Int J Periodontics Restorative Dent. 2011; 31(6):653-60. (Clinical study)

2 Instructions for Use. Geistlich Fibro-Gide®. Geistlich Pharma AG, Wolhusen, Switzerland. 3 Data on file. Geistlich Pharma AG, Wolhusen, Switzerland (Pre-clinical study). 4 Thoma DS, et al.: Clin Oral Implants Res. 2012; 23(12): 1333–9. (Pre-clinical study) 5 Thoma DS, et al.: J Clin Periodontol. 2016; 43(10): 874–85. (Clinical study). 6 Thoma DS, et al.: Clin Oral Implants Res. 2015; 26(3): 263–70. (Pre-clinical study). 7 Zeltner M, et al.: J Clin Periodontol. 2017; 44(4): 446–453. (Clinical study) 8 Huber S, et al.: J Clin Periodontol. 2018; 45(4):504512. (Clinical study) 9 Schulze-Späte U, Lee CT. Int J Periodontics Restorative Dent. 2019; 39(5):e181-e187. (Clinical study)

BACKGROUND

39


Publisher ŠGeistlich Pharma AG Business Unit Biomaterials Bahnhofstr. 40 6110 Wolhusen, Switzerland Tel. +41 41 492 55 55 Fax +41 41 492 56 39 www.geistlich-biomaterials.ch

6 0 2 0 4 6 / 2 0 0 2 /e n

More details via our sales partners: www.geistlich-pharma.com


Turn static files into dynamic content formats.

Create a flipbook
Issuu converts static files into: digital portfolios, online yearbooks, online catalogs, digital photo albums and more. Sign up and create your flipbook.