Elsevier

Biomaterials

Volume 22, Issue 7, April 2001, Pages 709-715
Biomaterials

Immobilization of bisphosphonates on surface modified titanium

https://doi.org/10.1016/S0142-9612(00)00234-9Get rights and content

Abstract

The efficiency of surface modifications on the immobilization of bisphosphonates on titanium was investigated with Ca-ion implantation and thin hydroxyapatite coatings. The ALP activity of osteoblastic cells and the inhibitory effects on the initial adherence of P. gingivalis were also evaluated using bisphosphonate-immobilized titanium. X-ray photoelectron spectroscopy analysis suggested that titanium surfaces modified with Ca-ion implantation and thin hydroxyapatite coatings caused the immobilization of bisphosphonate on titanium plates. The ALP activity of osteoblastic cells cultured on plates immobilized with bisphosphonate was almost the same as that of cells cultured on titanium plates, indicating that the bisphosphonate-immobilization showed no toxic effect on osteoblastic cells, and that it provides a favorable micro-environment with osteogenetic ability. Data of the adherence of oral bacteria showed that a bisphosphonate-immobilized titanium surface inhibited the initial adherence of P. gingivalis. These results indicate that the immobilization of bisphosphonates on titanium modified with Ca-ion implantation and thin hydroxyapatite coatings are useful for dental implants.

Introduction

Bisphosphonates are a new class of drugs that have been developed for use in treating several diseases related to bones, teeth, and calcium metabolism. These compounds are potent inhibitors of bone resorption, and inhibit soft tissue calcification in vivo [1], [2], [3], [4], [5], [6], [7]. In the dental field, the compounds prevent periodontal destruction [8], [9], [10], and decrease the formation of dental calculus [11], [12]. In vitro, many of the bisphosphonates inhibit the crystal formation of calcium phosphate [13], [14], [15], blocking the transformation of amorphous calcium phosphate into hydroxyapatite [16] and the dissolution of these crystals [1], [2].

All these effects are caused by the marked affinity of the bisphosphonates for solid-phase calcium phosphate, and their inhibition of the growth of calcium phosphate crystals. The bisphosphonates are chemisorbed on the surface of the microcrystallites of calcium hydroxyapatite and, in the manner of other known crystal growth poisons, prevent further crystal growth [17]. Bisphosphonates are also reported to alter the morphology of osteoclasts both in vitro and when administered in vivo [18], [19]. In addition, compared to pyrophosphate with its P–O–P bond (Fig. 1), which is shown to impair the crystallization of calcium phosphate from solution as well as the dissolution of these crystals, the P–C–P bond of the bisphosphonates is relatively stable to heat and most chemical reagents and is completely resistant to enzymatic hydrolysis.

On dental implants, the use of bisphosphonates is expected to promote osteogenesis at the bone tissue/implant interface by inhibiting activity of osteoclasts. Inhibition of the formulation of dental calculus on the surfaces of implants exposed to the oral cavity is also expected through the local action of the bisphosphonates. The immobilization of bisphosphonates on titanium implants is therefore considered important.

As methods of immobilizing bisphosphonates on titanium implants, surface modifications with calcium phosphates are useful, because bisphosphonates possess a marked affinity to these substances. Ion beam dynamic mixing (IBDM) has been introduced as a suitable technique for fabricating a thin and adherent calcium phosphate (Ca-P) layer [20], [21], [22], [23]. This method is a combination of ion implantation and physical vapor deposition (PVD) and has the advantages of producing defect-free transparent thin films, and excellent adhesion to the titanium substrate. Surface modifications with calcium ions are also useful by producing calcium compounds on titanium surfaces. Calcium-ion implantation has been introduced as a method of modifying the surface of titanium with stable calcium compounds [24], [25], [26].

This study was designed to evaluate (1) the influence of surface modifications with Ca-ion implantation and thin Ca-P coatings of hydroxyapatite on the immobilization of bisphosphonates on titanium, (2) the influence of the bisphosphonates-immobilization on the ALP activity of osteoblastic cells, and (3) inhibitory effects of the immobilization of bisphosphonates on initial adherence of oral bacteria.

Section snippets

Preparation of specimens

Commercially pure wrought titanium (cp-Ti) plates (JIS, Japan Industrial Specification H 4600, 99.9 mass% Ti, 10×10×1 mm) were used as the substrate material for modification. They were ground down to 1200 grit, finally polished using 0.3 μm alumina, and then ultrasonically cleaned with acetone. The titanium substrates were modified with calcium (Ca)-ion implantation and a calcium phosphate (Ca-P) coating as shown in Table 1.

The Ca-ion implantation was conducted with an accelerating voltage of 41 

XPS analysis

The elements detected by qualitative analysis were shown in Table 3. N and P were detected on the bisphosphonate-treated specimens of the Ca ion-implanted Ti (Ti-CaImp), the HA-coated Ti (Ti-HA), and the sintered HA. No bisphosphonate-originated elements were detected on the surface of the Ti specimens.

N1s and P2p spectra are shown in Fig. 4, Fig. 5, Fig. 6, Fig. 7 for both as-cleaned and 30-s argon-ion sputtered surfaces. The binding energies of N1s and P2p obtained from the

Discussion

It is reported that bisphosphonate increases the rate of early bone formation around dental implants by locally applying alendronate to HA-coated and machined titanium implants after implantation [30]. This method, however, did not directly immobilize the bisphosphonate on the implants. It is important to immobilize the bisphosphonates onto implant surfaces, because the efficiency of bisphosphonate must be maintained around the implants during implant functions through the local action of the

Acknowledgements

This study was supported in part by a Grant-in-Aid for Scientific Research No. 10671845 from The Ministry of Education, Science, Sports and Culture in Japan.

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