...a wish for faster and more predictable integration with the bone has been driving research...

REVOLUTIONARY SURFACE TREATMENT FOR BONE ANCHORED IMPLANTS

Tell us a little bit about the background of the research team you work with and your company.

The chemistry was developed by the group of Prof. Graetzel and the proof-of-concept was carried out by the osteoporosis research groups of late Dr. Harald Guenther (University of Bern, Switzerland) and Professor René Rizzoli

(University Hospital of Geneva, Switzerland). At the end of this first series of testing, the process feasibility and significantly higher bone formation and bone-implant fixation were proven.

With these results at hand, I founded the company Nano Bridging Molecules as a spin-off of the University of Geneva and the EPFL to develop the technology into a marketable product.

LAST MAY, AT THE MIS INTERNATIONAL CONFERENCE IN BARCELONA, DR. BJORN-OWE ARONSSON INTRODUCED THE B+ SURFACE TO THE ENTHUSIASTIC AUDIENCE. THIS PAST MARCH, AT THE IDS IN COLOGNE, MIS OFFICIALLY LAUNCHED THIS EXCITING NEW ADVANCEMENT.

The following interview presents a fascinating account of the development process and unique cooperation between MIS and Nano Bridging Molecules.

05 MNEWS 3rd Quarter, 2017

Knowing the importance and the need for solid scientific data bringing the product to market, we then decided to perform additional testing. In particular, we carried out a large animal study in sheep, in collaboration with the group of Prof. Brigitte von Rechenberg (University of Zürich, Switzerland) and we initiated a multicentre clinical study, involving several private clinics and universities (notably University of Geneva and Bern).

What led your team to do research on the B+? Is there a real need for a better connection between titanium and bone?

Titanium is used as implant material due to its inertness and good acceptance by the body. Over the years, however, a wish for faster and more predictable integration with the bone has been driving research around the importance of the surface structural and chemical properties. While a specific range of micro structures have been seen to benefit the early integration of an implant, the chemistry has not been tailored to meet the need of specific bio-chemical interactions. With the initial results from testing of the B+ surface it was discovered that for the first time, specific bio-chemical bonding can be obtained already at the very early healing phase after implantation. Indeed mineralised bone matrix was observed to be formed by the bone cells (osteoblasts) in direct contact to the B+ surface. During the maturing of the bone, increasing bonding force was observed as well as a strong interface after a long time. To evidence the long-time effectiveness of the bone bonding to the implant surface, a series of removal torque tests were carried out. Not only were the forces needed to remove the implant higher for the B+ surface, but most significantly the breakage of the bone occurred a few micrometers away from the implant surface, i.e. in the bone itself.

To the contrary, without the B+ surface, the interface between bone and implant was destroyed by the removal forces. It can be speculated that if an implant in everyday use is overloaded and the interface is somewhat fractured, the B+ surface will have the potential to remodel the bone and heal the fracture. Such healing is less likely to occur if the actual interface between bone and the traditional implant is destroyed. Other advantages of the B+ surface include its inherent hydrophilic nature, which leads to a natural interaction with proteins and cells. While a hydrophobic surface will cause a denaturation of the first proteins reaching the implant surface, leading to an increased initial foreign-body reaction. In contrast, B+ may lower the foreign-body reaction and appear more ‘bone-like’ from the implantation moment. The ultimate goal is of course to provide the patients with the best implant solution in both short and long term.

What was your process for creating this unique surface?

After the initial idea was given, the development process was divided into three parts, feasibility and proof-of-concept, clinical safety, and finally product development with regulatory approvals. During all these phases the company has been supported by world leading scientists and clinical specialists. Those specialists have been concretely participating in providing pre-clinical and clinical test results, which to the large extent they have subsequently published. In addition, today NBM has an ISO certified production laboratory in Switzerland, led by the founder together with a couple of eminent chemists and a finance and administration responsible.

What interested you in MIS?

When we started to plan the commercialisation, we set the goal to search to partner with one of the five most eminent implant manufacturers in the world. The strong leading position of MIS, in combination with its reputation of being determined and fast in implementing new products and solutions made them very attractive as a commercialisation partner for NBM.

06 MNEWS 3rd Quarter, 2017

08 MNEWS 3rd Quarter, 2017

How did cooperation with MIS begin?

NBM engaged with a firm to find a suitable partner. Together we engaged in initial talks and presentations of the SurfLink® surface at conferences and by personal contacts. Interesting discussions were initiated with several potential partners, and amongst those MIS. Through the efficient actions of the R&D team, MIS was the quickest in responding with an elaborate plan for rapid industrial implementation and commercial product launch. After a first visit to the MIS headquarters and a process validation, a commercial agreement was signed. The B+ production process implementation was initiated and regulatory approvals prepared.

How i s th i s monolayer of m o l e c u l e s different from t r ad i t i ona l m e t h o d s o f su r face treatment and what, if any, are the safety

implications?

This mono- layer of mul t i -phosphonated molecules are uniquely

combine several properties in a single molecule: the chemical structure creates a

‘bone-like’ surface on the implant, bone cells have been observed to create new bone

tissue directly on the surface, avoiding any buffering protein interface. They further allow for the creation of strong chemical bonding between bone tissue and the implant. The mono-layer is chemically and enzymatically stable in relevant physiological environments which means a long term stability without any degradation products (other coatings often

lack stability, especially in inflammatory situations with low pH). In terms of

safety, the increased stability and strong bonding of the bone-implant interface, in combination with the biomimicking properties give an increased safety for the patient. NBM clinical studies have not shown any safety concern up to date.

What are some other applications

you are exploring for this surface?

Stable bone-bonding is sought after in most of the uses of implants; for hip, knee, shoulder and other joint replacements, SurfLink® offers the potential of improved clinical outcome. Currently, we are exploring the use of SurfLink® for restoring vertebral stability with screws or artificial discs. Interestingly, SurfLink® can be used on all metal-oxides and ceramics, opening up for the use of materials with other properties than Titanium, while still enabling them to have the same effective biomimicking surface.

Dr. Björn-Owe Aronsson

Dr. Aronsson, the principle founder of NBMolecules®, is currently serving as its Chief Executive Officer. Through his leadership, the company has gone through all phases from proof-of-concept, clinical validation, to producing CE-marked products and concluding commercialization agreements. Dr. Aronsson graduated in 1986 with an M.Sc. degree in Engineering Physics from Chalmers University of Technology, Gothenburg, Sweden and received his Ph.D. from the same institute in 1995. He came to the University of Geneva as a Post Doc and continued as Researcher with several national and European research grants. He has over 18 years of research and development experience within the field of device-to-tissue interface. Prior to NBM, Dr. Aronsson also served as a consultant to Nobel Biocare AB in the area of implant surface chemistry composition following cleaning and sterilization (quality control). Dr. Aronsson has published over 35 papers in peer reviewed academic and industry publications. He is a regular speaker and has otherwise contributed at over 100 conferences. Dr. Aronsson has participated in research projects which have given rise to four industry patents.

...bone cells have been observed to create new bone tissue directly on the surface, avoiding any buf fer ing pro te in interface.

09 MNEWS 3rd Quarter, 2017

[D.U. Duddeck et al. Europerio 8, London, June 3-6, 2015]