IRUCAA@TDC : Effects of dental implant surface on bone integration

Posted at the Institutional Resources for Unique Collection and Academic Archives at Tokyo Dental College, Available from http://ir.tdc.ac.jp/

Title

Effects of dental implant surface on bone

integration

Author(s)

John, A Jansen

Journal

歯科学報, 111(6): 604-607

URL

http://hdl.handle.net/10130/2655

Right

Introduction

During the last decades, the replacement of missing teeth with implant­supported prostheses has be-come a widely accepted and routinely used treatment modality for the rehabilitation of fully and partially edentulous patients. The underlying biological phenomenon of osseointegration was first described by the two research groups of Bra!nemark（１９６９）and Schroeder（１９７６）and is thought to be a biological reaction cascade dividable into three distinct phases. The first and most important healing phase, osteoconduction, relies on the recruitment and migration of osteogenic cells to the implant surface.

It has to be noticed that good long­term clinical outcomes for oral implants have been reported espe-cially when the implants were installed in bone of high density and a two­stage surgical procedure was used. In more challenging situations such as low bone densities, grafted bone as well as immediate or early loading, increased failure rates of implants with smooth surfaces have been reported. As a consequence, im-plant surface modification has been proposed as an approach to accelerate bone healing. Surface modifica-tions of dental titanium implants are accomplished by roughening or by altering the chemical composition. Up to now, coating of dental titanium implants with calcium phosphate（CaP）ceramic is still the most fre-quently used method for changing the chemical surface composition（Le Guéhennec ２００７）．Consefre-quently, CaP­coatings have been used to maximize bone formation. Already more than a decade ago numerous studies have been published about the biological advantage of such coated implants（Jansen １９９９）．The study results demonstrated an increased mechanical interlocking and an increased percentage of bone con-tact for CaP surfaced implants, when compared with non­coated titanium implants. However, although promising effects of calcium phosphate coatings on bone­to­implant response are known for decades, the clinical performance of these coatings remains controversial（Schwartz­Arad ２００５）．Particularly, coating degradation might be related to supplementary crestal bone loss.

Calcium phosphate（CaP）coatings

Several techniques have been developed and are used to coat CaP ceramics onto titanium implant

sur-Effects of dental implant surface on bone integration

John A. Jansen, DDS, PhD

Professor and Chairman Department of Biomaterials, Dentistry Radboud University Nijmegen Medical Center

Figure１．Scanning electron micrographs of CaP coating morphologies of（left）plasma spray coating，（middle）RF magne-tron sputter coating, and（right）electrospray deposition coating（bar represents １０μm）．

国際シンポジウム「４０年を迎えたインプラントの光と影」 ６０４

faces, but plasma spraying is still the most commonly used method（Figure １）．However, for conventional plasma spraying numerous powder characteristics and process parameters must be carefully controlled to consistently deposit high­quality coatings. This implies that only close control of a multitude of factors such as velocity of the plasma flame, powder particle size, and plasma temperature, can finally guarantee a mini-mum control of physical and chemical coating characteristics as adherence, thickness, porosity, crystallinity, and roughness. Consequently, relevant limitations still persist in conventionally plasma sprayed CaP coat-ings.

Electrostatic spray deposition（ESD）

Therefore, researchers have been continuously inspired in the past two decades to explore alternative or complementary techniques for deposition of CaP coatings onto implant surfaces. In order to overcome the above mentioned drawbacks of plasma­sprayed coatings, various deposition methods have been proposed, including magnetron sputtering（Figure １），electrophoretic deposition, sol­gel deposition, pulsed laser deposition, ion beam deposition, biomimetic deposition and electrolytic deposition（Jansen １９９９）．A recently introduced novel deposition technique is Electrostatic Spray Deposition（ESD）（Leeuwenburgh ２００６）．ESD involves atomization of a precursor solution by applying a high voltage to the liquid surface, which then dis-perses into an aerosol spray of micron­sized, charged droplets（＜１０μm）．This is accomplished by pump-ing the solution through a nozzle. Usually a spherical droplet is then formed at the tip of the nozzle, but when a high voltage is applied between nozzle and substrate, this droplet transforms into a conical shape and fans out to form a spray of highly charged droplets. These charged droplets are attracted towards a grounded substrate, where a thin biofilm is formed after solvent evaporation.

Using ESD, it is possible to obtain thin CaP layers with an extremely wide range of chemical and morpho-logical characteristics. Various CaP phases and phase mixtures can be deposited and a broad diversity of coating morphologies can be produced by varying deposition parameters related to the ESD­apparatus and /or the precursor solutions. Typical ESD­derived, reticular coating morphologies consist of a porous net-work of variable pore size, as shown in Figure １.

Organic­inorganic composite coatings

Since bone is composed of an organic matrix（of which ９０％ are collagenous proteins）strengthened by an inorganic CaP phase（carbonated hydroxyapatite），research during the last decade has focused on the development of bio­inspired composite coatings that resemble the unique nano­composite structure bone tissue, thereby offering an added value over coatings consisting of merely organic or inorganic components. Composite coatings made of both collagen and CaP have therefore generated a great deal of interest for im-plant surface modification. Moreover, CaP coatings have been combined with biomolecules that elicit spe-cific cellular responses（cytokines, growth factors, antibiotics, etc．）to enhance bone formation at the im-plant surface.

Most techniques used to prepare inorganic CaP coatings are performed either at extremely high tem-peratures or under extremely non­physiological conditions, which preclude the incorporation of biomole-cules（Jansen１９９９）．Investigations have attempted to circumvent this difficulty by adsorbing biological agents onto the surfaces of preformed inorganic layers（de Jonge ２００８）．However, these superficially ad-sorbed molecules will be rapidly released in an uncontrollable single burst upon implantation. Hence, coat-ing procedures that incorporate biomolecules into the CaP coatcoat-ing create a more sustained release profile and are therefore of high interest. In this way, the molecules can both sustain their biological activity for a

considered period of time and support the mechanical properties of the coating in case of structural ECM components such as collagen. The electrostatic spray deposition process is among the most promising tech-niques for generating organic­inorganic composite coatings on implant materials due to their physiological process conditions.

Electrosprayed enzyme coatings

In an attempt to mimic the biphasic biomineralization process of bone, both the enzyme ALP and calcium phosphate（CaP）can be immobilized onto titanium implants, thereby triggering enzymatically and physi-cochemically controlled biomineralization pathways. ALP, CaP and ALP­CaP composite coatings with pre-served functionality of ALP were successfully deposited using the ESD technique（de Jonge ２００９）．In vitro soaking studies in cell culture medium revealed that crystal growth initially proceeded at a faster rate on CaP­coatings than on ALP­containing coatings, but mineral deposition onto ALP­coated titanium caught up with the calcification behavior of CaP coatings upon long­term soaking. Cell culture experiments with osteoblast­like cells, however, demonstrated an opposite effect in mineral deposition on the electrosprayed CaP and ALP coatings. The ALP­CaP composite coatings showed delayed proliferation as well as acceler-ated mineralization in comparison to cells cultured on the CaP­ and uncoacceler-ated titanium. In conclusion, these in vitro results showed that the osteogenic potential of titanium implant surfaces can be stimulated by ALP ­containing coatings.

Collagen­calcium phosphate composite coatings

A composite coating composed of collagen protein and CaP minerals is considered to be bioactive and may enhance bone growth and fixation of titanium implant materials. Collagen, being the main organic com-ponent of the ECM, induces positive effects concerning cellular adhesion, proliferation, and differentiation of many cell types in culture. Furthermore, collagen exhibits high in vivo biodegradability and excellent bio-compatibility.

Nanometer­thick CaP and collagen­CaP composite coatings（＜２００ nm）were successfully fabricated on titanium discs by electrospraying stable suspensions of crystalline CaP nanoparticles and collagen（de Jonge ２０１０）（Figure ２）．Subsequently, the biological behavior of CaP and col­CaP composite coatings was evaluated. No differences in in vitro responses for

variable coating thicknesses were observed, but the results revealed that coatings of only ５０ nm in thickness exerted an osteogenic effect on cultured osteoblast­like cells. Compared to the CaP­coated and control groups, the collagen­CaP coatings sig-nificantly enhanced mineralization onto the titanium implant surfaces.

Future perspectives

The long­term success of bone­interfacing im-plants requires rigid fixation of the implant within the host bone site. Mineralization is the fundamental aspect that enables implants to remain stable in place even when force is applied. It is recognized

Figure ２．Scanning electron micrograph of a ５０ nm thick electrosprayed nanoCaP coating on tita-nium. The nanoCaP particles can be seen to be entangled with the collagen fibrils.

国際シンポジウム「４０年を迎えたインプラントの光と影」 ６０６

that mineralization/apatite nucleation starts associated with either extracellular matrix vesicles or collagen （in conjunction with matrix proteins）．The opportunities for the future are to apply the knowledge on biomineralization towards the development of novel biologically­based coatings. In our studies, both organic components that take part in the process of biomineralization were already deposited onto implant surfaces, i.e. ALP, as present within in the matrix vesicles to increase the local phosphate concentration required for physiological mineralization, and collagen, where crystals are formed at discrete sites of the collagen fibers. In our studies, ALP and collagen were deposited in combination with CaPs. For future research, it would be of high interest to deposit coatings that further mimic the bone mineralization process. In the case of matrix vesicles, the influx of Ca２＋

and PO４３­ ions is mediated by proteins in order to increase these local ion

con-centrations for apatite formation. Synergistically combining ALP with calcium binding matrix proteins such as osteopontin, bone sialoprotein（BSP），and osteonectin may lead to advanced biomedical coatings for bone implantology. Further promising synergistic surface modifications include the immobilization of collagen combined with calcium and phosphate binding proteins to induce mineral deposition and thereby improving implant fixation into bone tissue.

References

１．Bra!nemark PI , Adell R , Breine U , Hansson BO , Lindström J and Ohlsson A. Intraosseous anchorage of dental prostheses. I. Experimental studies.Scandinavian Journal of Plastic and Reconstructive Surgery ３，

８１­１００（１９６９）．

２．De Jonge LT, Leeuwenburgh SCG, Wolke JGC and Jansen JA. Organic­inorganic surface modifications for titanium implants.Pharamaceutical Research，２５，２３５７−２３６９（２００８）．

３．De Jonge LT, Leeuwenburgh SCG, Van den Beucken JJJP, Wolke JGC and Jansen JA. Electrosprayed enzyme coatings as bio­inspired alternatives to bioceramic coatings for orthopedic and oral implants.

Ad-vanced Functional Materials，１９，７５５−７６２（２００９）．

４．de Jonge LT, Leeuwenburgh SC, van den Beucken JJ, te Riet J, Daamen WF, Wolke JG, Scharnweber D and Jansen JA. The osteogenic effect of electrosprayed nanoscale collagen/calcium phosphate coatings on titanium.Biomaterials，３１，２４６１−２４６９（２０１０）．

５．Jansen JA , Hulshoff JEG and Wolke JGC Calcium Phosphate（CaP）ceramic surface coatings and their significance., In : Proceedings of the ３rd European Workshop on Periodontology Berlin : Quintessenz，７３−８８ （１９９９）．

６．Leeuwenburgh SC, Wolke JG, Siebers MC, Schoonman J and Jansen JA. In vitro and in vivo reactivity of porous, electrosprayed calcium phosphate coatings.Biomaterials ２７，３３６８−３３７８（２００６）．

７．Le Guéhennec L, Soueidan A, Layrolle P and Amouriq Y. Surface treatments of titanium dental implants for rapid osseointegration.Dental Materials，２３，８４４−８５４（２００７）．

８．Lind M, Overgaard S, Glerup H, Soballe K and Bunger C. Transforming growth factor­beta１ adsorbed to tricalciumphosphate coated implants increases peri­implant bone­remodeling. Biomaterials ２２，１８９− １９３（２００１）．

９．Schroeder A, Pohler O and Sutter F. Gewebereaktion auf ein Titan­Hohlzylinderimplantat mit Titan­ Spritzschichtoberfläche.Schweizer Monatsschrift für Zahnheilkunde，８６，７１３−７２７（１９７６）

１０．Schwartz­Arad D , Mardinger O , Levin L , Kozlovsky A and Hirshberg A. Marginal bone loss pattern around hydroxylapatite­coated versus commercially pure titanium implants after up to １２ years of fol-low­up.International Journal of Oral and Maxillofacial Implants，２０，２３８−２４４（２００５）．