Dental implants: why don’t they fail?

Henk J. Busscher

The WJ Kolff Institute for Biomedical Engineering and Materials ScienceUniversity of Groningen and University Medical Center Groningen

Groningen, The Netherlands

W.J. Kolff: one of the most successful translators of new ideasinto clinical practice

DISCLAIMER FOR EVERYTHING I EVER DID, SAID OR WROTE:

I’m the director-owner of a consulting company “Scientific and Applied SurfaceAdvice”. SASA BV has been consulting for or is currently consulting for: ATOS Medical, Bausch & Lomb, Braun-Oral B, Colgate-Palmolive, DePuy Orthopaedics, GABA International, Henkel AG, Philips Sonicare, Procter & Gamble,Straumann International, Wrigley.

I have permission for my activities within SASA BV from the University of Groningen/University Medical Center Groningen.

I, nor SASA BV, have any financial interests in the companies that SASA BV consults for.

My academic work has been directly funded by or is currently funded byDSM, Ethicon, FCDF, Philips, SASA BV, Zorginnovatie BV.

My academic work has furthermore been funded by IOP milieutechnologie / Zware Metalen,(Senter), STW grants 07109, 07844, Eureka grants 72310, 2614, BMM-grant P4.01NANTICO (BMM is a Dutch public-private partnership co-funded by the Dutch Ministry of Economic Affairs) and FP-7 project FORAMP.

My academic work may have been directly or indirectly, but always unintentionally, influenced by the companies that SASA BV has consulted for, by industrial partners that have directly funded my academic work or by industrial partners in the public-private partnerships related to the grants that fund my academic work.

I CANNOT BE MORE SPECIFIC

AS I DO NOT KNOW

IF, WHEN, HOW AND WHY

MY BRAIN MAKES CERTAIN CONNECTIONS

BETWEEN BITS OF INFORMATION I HAVE.

Healthy aging involves more than growing old.

Loss of function is inevitablyassociated with aging,

yet considered unacceptablein the 21st century.

Often,functioning of the body is beyond natural repair,

due totrauma, (oncological) intervention surgery or wear.

“You should not be a coward if you want to grow old”

Prof.dr. Horst KlinkmannDean INFA

Or we need BIOMATERIALS!

“A non-viable material used in a medical device or implant,intended to interact with biological systems”

95+% of all biomaterials-implant patientsare happy patients.

The happy patient

There are unhappy patients

Trophies of failureTrophies of failure

On average, 5% of all biomaterial-implant patientsexperience severe complications, mainly due to INFECTION.

THE CAUSE: Per- and early post-operative contamination?

Doors open up to 60x during total hip arthroplasty for -coffee

-reading material

-urgencies.

Inadequate scrubbing of hands prior to surgery.

30% of instrumentation gets contaminated during surgery, hence 30% of patients leave OR with an infection.

Science 1987(237)1588-1595.

Biomaterial-Associated Infection: Locating the Finish Line in the Race for the Surface. Busscher HJ, et al., Science Translational Medicine 4(2012)1-11.

If peri-operative contaminationis the cause of implant failure:

Why do dental implants resist infection so effectively,whilst other implants sites do not?

a

b

1-6% 11-71%2%

WhyDo not all dental implants fail?

SALIVA?contains approximately 109 viable bacteria ml-1

CREVICULAR FLUID?content very similar to the one of serum

WOUND HEALING?fast in the oral cavity

BACTERIAL PRESENCE?high challenge concentrations including many opportunistic pathogens

IMMUNE SYSTEM?immunosuppressive commensals may prevent the immune system from becoming frustrated by the presence of a biomaterial

BIOMATERIAL

SURFACE

BACTERIATISSUE CELLS

Biomaterial-centered infection:microbial adhesion versus tissue integration.

Gristina AG, Science 237(1987)588-1595.

Microbial biofilm growth vs. tissue integration: "the race for the surface" experimentally studied. Subbiahdoss G, et al., Acta Biomaterialia 5(2009)1399-1404.

Tissue cells againstbacteria

1. Bacterial adhesion to 103 cm-2 in modified medium

2. Seeding of tissue cells (20000/cm2)

3. Cell adhesion for 1.5 h

4. Co-culture in modified medium for 48 h

5. Fixated, staining with TRITC-Phalloidin, CLSM analysis

6. Image analysis using Scion software

1. Area covered by tissue cells

2. Area/cell

3. Number of tissue cells

Peri-operative co-culture model

98% DMEM+FBS and 2% TSB gives the osteoblasts an advantage over bacteria

A modified culture medium

staphylococci

osteoblasts

HG fibroblasts against supra-gingival oral bacteria

The effect of contaminating bacteriaon tissue integration depends

on the material involved.

Soft tissue integration versus early biofilm formationon different dental implant materials. Zhao B, et al.,DENTAL MATERIALS 30(2014)716–727.

HG fibroblasts against supra-gingival oral bacteria

*Clinical and microbiological characteristics of peri-implantitis cases: a retrospective multicentre study. Charalampakis G, et al., Clin Oral Impl Res 23(2012)1045-54.

Clinical data are scarce and a recent multi-center study (281 patients and six different implant types) concluded that peri-implantitis develops earlier in implants with rough surfaces*.

Thus our co-culture study not only supports clinical data,but clinical data also support our co-culture model.

Depending on the substratum,low levels of contaminating bacteria may stimulate tissue integration!!??

Osteoblasts against S. epidermidis

Simultaneous interaction of bacteria and tissue cells with photocatalytically activated, anodized titanium surfaces. Yue C, et al., BIOMATERIALS 35(2014)2580-2587.

An in vitro investigation of bacteria-osteoblast competition on oxygenplasma-modified PEEK. Rochford ETJ, et al., J Bio-med Mat Res (2014). DOI: 10.1002/jbm.a.35130

Streptococcus mutans antigen I/II binds to α5β1 integrins via its A-domain and increases β1 integrinsexpression on periodontal ligament fibroblast cells. Engels-Deutsch M, et al., Arch Oral Biol 56(2011)22-28.

Please read also:

Bacteria hijack integrin-linked kinase to stabilize focal adhesions and block cell detachment. Kim M. et al., Nature 459, 578, 2009.

Biomaterial implants and devices are alwaysat post-surgical risk of infection

from bacterial contamination spreadingthrough the bloodstream from infections elsewhere in the body.

“Consult your physician if you

- You have laryngitis, open or infected wounds

- You need to have endodontic treatment, have calculus removed or tooth extraction”

Busscher HJ, et al., Biomaterial-Associated Infection: Locating the Finish Line in the Race for the Surface. Science Translational Medicine 4(2012)1-11.

Peri-operative model

Post-operative model

1. Seed tissue cells (20000/cm2)

2. Cell adhesion for 1.5 h and growth for 24 h

3. Bacterial adhesion to 103 cm-2 in modified medium

4. Co-culture in modified medium for 24 h

5. Fixated, staining with TRITC-Phalloidin, CLSM analysis

6. Image analysis using Scion software

1. Area covered by tissue cells

2. Area/cell

3. Number of tissue cells

Post-operative contaminationco-culture model

Biomaterial implants and devices are alwaysat post-surgical risk of infection

from bacterial contamination spreadingthrough the bloodstream from infections elsewhere in the body.

“Consult your physician if you

- You have laryngitis, open or infected wounds

- You need to have endodontic treatment, have calculus removed or tooth extraction”

What if you have a dental implant?

Whydon’t all dental implants fail?

Loss of the soft tissue seal: peri-implant mucositis

Peri-implantitis with bone loss

Sub-gingival oral pathogenschallenging an osteoblast layeron dental implant materials

Osteoblast integration of dental implant materials after challenge by sub-gingival bacteria- a co-culture study in vitro. Zhao B, et al., to be submitted.

On some materials, tissue cells do not care about bacterial challenges.

then ............

BIOMATERIAL

SURFACE

BACTERIATISSUE CELLS

If the fate of an implantis a race for the surface,

A SIMPLE, EVOLUTIONARY PREREQUISITE!

1. Immunosuppressive oral commensals prevent the immune system from becoming frustrated by a biomaterials presence

2. Oral tissue cells are more used to live togetherwith colonizing bacteria than naive peri-implant tissue surrounding e.g. a total hip arthroplasty

HYPOTHESIS:not all dental implants fail because of

The implant infection paradox: Why do some succeed when others fail?Yue C, et al., eCM, submitted.

The implant infection paradox: Why do some succeed when others fail?

1. The succes of dental implants is due to the evolutionary achievements of A. Accostuming oral tissue cells to living together with bacteriaB. A tolerant immune system, acting in a balanced way to the presence of bacteria and foreign bodies.

2. There may be things to learn from the succes of dental implants,that we can use to create infection-resistant conditions in recipients of other types of biomaterial implants and devices.

The implant infection paradox: Why do some succeed when others fail?Yue C, et al., eCM, submitted.