Hydroxyapatite-coated Titanium Implants Research Articles

Calcium fructoborate coating of titanium-hydroxyapatite implants by chemisorption deposition improves implant osseointegration in the femur of New Zealand White rabbit experimental model.

Background: The identification of biocomposites that improve cell adhesion and reduce bone integration time is a great challenge for implantology and bone reconstruction. Aim: Our aim was to evaluate a new method of chemisorption deposition (CD) for improving the biointegration of hydroxyapatite-coated titanium (HApTi) implants. CD method was used to prepare a calcium fructoborate (CaFb) coating on a HApTi (HApTiCaFb) implant followed by evaluation of histological features related to bone healing at the interface of a bioceramic material in an animal model. Methods: The coating composition was investigated by high-performance thin-layer chromatography/mass spectrometry. The surface morphology of the coating was studied by scanning electron microscopy (SEM), before and after the in vitro study. We implanted two types of bioceramic cylinders, HApTi and HApTiCaFb, in the femur of 10 New Zealand White (NZW) rabbits. Results: The release of CaFb from HApTiCaFb occurred rapidly within the first three days after phosphate-buffered saline immersion; there was then a linear release for up to 14 days. SEM analysis showed similar morphology and particle size diameter for both implants. Around the porous HApTiCaFb implant, fibrosis and inflammation were not highlighted. Conclusions: Easily applied using CD method, CaFb coatings promote HApTi implant osseointegration in the femur of NZW rabbits.

Local administration with tauroursodeoxycholic acid could improve osseointegration of hydroxyapatite-coated titanium implants in ovariectomized rats.

Despite advances in the pathogenesis of Tauroursodeoxycholic acid (TUDCA) on bone, the understanding of the effects and mechanisms of bone osseointegration in TUDCA-associated Hydroxyapatite (HA)-coated titanium implants remains poor. Therefore, the present work was aimed to evaluate the effect of local administration with TUDCA on HA-coated titanium implants osseointegration in ovariectomized(OVX) rats and further investigation of the possible mechanism. Twelve weeks after bilateral ovariectomy, all animals were randomly divided into three groups: sham operation(Sham) group, OVX group and TUDCA group, and all the rats from Sham group and OVX group received HA implants and animals belonging to group TUDCA received TUDCA-HA implants until death at 12 weeks. The bilateral femurs of rats were harvested for evaluation. TUDCA increased new bone formation around the surface of titanium rods and push-out force other than group OVX. Histology, Micro-CT and biochemical analysis results showed systemic TUDCA showed positive effects than OVX group on bone formation in osteopenic rats, with beneficial effect on via activation OPG/RANKL pathway and BMP-2/Smad1 pathway and microarchitecture as well as by reducing protein expression of TNF-α and IFN-γ. The present study suggests that local use of TUDCA may bring benefits to the osseointegration of HA-coated titanium implants in patients with osteoporosis, and this effect may be related to the inhibition of inflammatory reaction and promotion of osteogenesis.

Taking Hydroxyapatite-Coated Titanium Implants Two Steps Forward: Surface Modification Using Graphene Mesolayers and a Hydroxyapatite-Reinforced Polymeric Scaffold.

Coating with hydroxyapatite (HAP) presents a mainstream strategy for rendering bioinert titanium implants bioactive. However, the low porosity of pure HAP coatings does not allow for the infiltration of the surface of the metallic implant with the host cells. Polymeric scaffolds do enable this osseointegration effect, but their bonding onto titanium presents a challenge because of the disparity in hydrophilicity. Here, we demonstrate the inability of a composite scaffold composed of carbonated HAP (CHAP) nanoparticles interspersed within electrospun ε-polycaprolactone (PCL) nanofibers to bind onto titanium. To solve this challenge, an intermediate layer of graphene nanosheets was deposited in a pulsed laser deposition process, which facilitated the bonding of the scaffold. The duration of the deposition of graphene (0, 5, 10, 15, and 20 min) and the thickness of its mesolayer affected numerous physical and chemical properties of the material, including the surface atomic proportion of carbon bonds, the orientation and interlinking of the polymeric nanofibers, and the surface roughness, which increased in direct proportion with the thickness of the graphene mesolayer. Because the polymeric scaffold did not adhere onto the surface of pure titanium, no cells were detected growing on it in vitro. In contrast, human fibroblasts adhered, spread, and proliferated well on all the substrates sputtered with both graphene and the composite scaffold. The orientations of cytoskeletal filopodia and lamellipodia were largely determined by the topographic orientation of the nanofibers and the geometry of the surface pores, attesting to the important effects that the presence of a scaffold has on the cellular behavior. The protection of titanium from corrosion in the simulated body fluid (SBF) was enhanced by coating with graphene and the composite scaffold, with the most superior resistance to the attack of the corrosive ions being exhibited by the substrate subjected to the shortest duration of the graphene deposition because of the highest atomic ratio of C-C to C-O bonds detected in it. Overall, some properties of titanium, such as roughness and wettability, were improved monotonously with an increase in the thickness of the graphene mesolayer, while others, such as cell viability and resistance to corrosion, required optimization, given that they were diminished at higher graphene mesolayer thicknesses. Nevertheless, every physical and chemical property of titanium analyzed was significantly improved by coating with graphene and the composite scaffold. This type of multilayer design evidently holds a great promise in the design of biomaterials for implants in orthopedics and tissue engineering.

Local administration of aspirin improves osseointegration of hydroxyapatite-coated titanium implants in ovariectomized rats through activation of the Notch signaling pathway.

Osteoporosis-induced impaired bone regeneration would result in compromised osseointegration of hydroxyapatite-coated titanium and high rate of implant failure. Local administration of aspirin prom...

Melatonin improves the osseointegration of hydroxyapatite-coated titanium implants in senile female rats.

The aim of this study was to confirm the effect of the systemic administration of melatonin on hydroxyapatite-coated titanium (HA-Ti) implants in senile osteopenic rats. For this study 24-month-old female Sprague-Dawley rats were used. The animals were randomly divided into two groups: a control group and a melatonin group and the bilateral femurs of all the rats received HA-Ti implants. Animals in the melatonin group received treatment with melatonin (30 mg/kg day). After a 12-week healing period, rats in the melatonin group revealed improved osseointegration compared to the control group, with the bone area ratio (BAR) and bone to implant contact (BIC) increased by 1.87-fold and 1.65-fold in histomorphometry, the quantitative results of implant osseointegration and peri-implant trabeculae, such as ahigher bone volume per total volume (BV/TV), trabecular number (Tb.N), the mean connective density (Conn.D), trabecular thickness (Tb.Th), and alower trabecular spacing (Tb.Sp) in micro-computed tomography (CT) evaluation and the maximum push-out force by 1.75-fold in push out tests. Additionally, compared with the control group, melatonin could significantly up-regulate the expression of the runt-related transcription factor 2 (Runx2), osteocalcin (OC) and osteoprotegerin (OPG) genes and down-regulate the expression of the RANKL gene. These findings suggest that systemic administration with melatonin is useful to improve the fixation of HA-coated implants even in osteopenic rats through promoting Runx2, OC and OPG gene expression and inhibiting RANKL gene expression.

Local administration with silymarin could increase osseointegration of hydroxyapatite-coated titanium implants in ovariectomized rats

As hydroxyapatite has good osteoconductive properties, it is used as coating material for the implants in cementless arthroplasty. However, its effect is not sufficient for osteoporotic bone. Silym...

Effects of Aloe Vera Gel Extract in Doped Hydroxyapatite-Coated Titanium Implants on in Vivo and in Vitro Biological Properties.

Hydroxyapatite-coated titanium alloys have been a popular choice as bone implants for load-bearing applications for the compositional similarity of hydroxyapatite to natural bone. The limited osteoinductive properties exhibited by the hydroxyapatite (HA) coatings have led to the incorporation of growth factor or dopants for improved osseointegration. This study aims to investigate the effects of a naturally occurring aloe vera gel extract, acemannan, in doped hydroxyapatite coatings on the in vitro osteoblast cell viability and in vivo new bone formationin a rat distal femur model. Silver oxide and silica-doped hydroxyapatite coatings were developed by the induction plasma spray coating method on Ti alloys to introduce antibacterial properties along with induction of angiogenic properties, respectively. The doped coating was further consecutively dip coated with acemannan to analyze its effects on the in vivo early stage osseointegration and chitosan to control the burst release of the acemannan from the calcium phosphate matrix. The results show controlled release of acemannan from the chitosan coatings, with enhanced osteoblast cell viability by the incorporation of acemannan in vitro. Improved osseointegration with a seamless implant interface and improved new bone formation was noted by the acemannan and chitosan coating in vivo, 5 weeks after implantation. Our results demonstrate the efficacy of a combination of natural medicine and naturally occurring polymer in a doped hydroxyapatite-coated titanium implant on the bone tissue regeneration for load-bearing orthopedic applications.

Effects of polycaprolactone on alendronate drug release from Mg-doped hydroxyapatite coating on titanium

The scientific objective of this study was to understand the influence of PCL coating on alendronate drug release kinetics in vitro. Our hypothesis was PCL coating would minimize burst release of alendronate from plasma sprayed Mg-doped hydroxyapatite (HA) coated commercially pure titanium (CpTi) samples. In the US alone, over 44 million women and men aged 50 and older are affected by osteoporosis which can lead to replacement and/or revision surgeries. Alendronate is a widely-used drug for treating osteoporosis and would be an ideal drug to be loaded and released from these replacement systems. Initial burst release is a common phenomenon for the most drug loaded devices. To modulate the release kinetics, a biodegradable polymer, polycaprolactone (PCL), coating with slow degradable kinetics was employed. Samples with 2 and 4 wt% PCL showed about 34% and 26% release of alendronate within the first 24 h, respectively, compared to 75% burst release without any PCL coating. With the addition of a PCL coating, a controlled release kinetics of alendronate was achieved from HA coated titanium implants, which can potentially impact millions of patients worldwide having compromised bone due to osteoporosis.

Effects of combined human parathyroid hormone (1-34) and menaquinone-4 treatment on the interface of hydroxyapatite-coated titanium implants in the femur of osteoporotic rats.

The objective of this study was to investigate the effects of human parathyroid hormone (1-34) (PTH1-34; PTH) plus menaquinone-4 (vitamin K2; MK) on the osseous integration of hydroxyapatite (HA)-coated implants in osteoporotic rats. Ovariectomized female Sprague-Dawley rats were used for the study. Twelve weeks after bilateral ovariectomy, HA-coated titanium implants were inserted bilaterally in the femoral medullary canal of the remaining 40 ovariectomized rats. All animals were then randomly assigned to four groups: Control, MK, PTH and PTH+MK. The rats from groups MK, PTH and PTH+MK received vitamin K2 (30mg/kg/day), PTH1-34 (60μg/kg, three times a week), or both for 12weeks. Thereafter, serum levels of γ-carboxylated osteocalcin (Gla-OC) were quantitated by ELISA and the bilateral femurs of rats were harvested for evaluation. The combination of PTH and MK clearly increased the serum levels of Gla-OC (a specific marker for bone formation) compared to PTH or MK alone. The results of our study indicated that all treated groups had increased new bone formation around the surface of implants and increased push-out force compared to Control. In addition, PTH+MK treatment showed the strongest effects in histological, micro-computed tomography and biomechanical tests. In summary, our results confirm that treatment with PTH1-34 and MK together may have a therapeutic advantage over PTH or MK monotherapy on bone healing around HA-coated implants in osteoporotic rats.

A comparative study of zinc, magnesium, strontium-incorporated hydroxyapatite-coated titanium implants for osseointegration of osteopenic rats

Surface modification techniques have been applied to generate titanium implant surfaces that promote osseointegration for the implants in cementless arthroplasty. However, its effect is not sufficient for osteoporotic bone. Zinc (Zn), magnesium (Mg), and strontium (Sr) present a beneficial effect on bone growth, and positively affect bone regeneration. The aim of this study was to confirm the different effects of the fixation strength of Zn, Mg, Sr-substituted hydroxyapatite-coated (Zn-HA-coated, Mg-HA-coated, Sr-HA-coated) titanium implants via electrochemical deposition in the osteoporotic condition. Female Sprague–Dawley rats were used for this study. Twelve weeks after bilateral ovariectomy, all animals were randomly divided into four groups: group HA; group Zn-HA; group Mg-HA and group Sr-HA. Afterwards, all rats from groups HA, Zn-HA, Mg-HA and Sr-HA received implants with hydroxyapatite containing 0%, 10% Zn ions, 10% Mg ions, and 10% Sr ions. Implants were inserted bilaterally in all animals until death at 12weeks. The bilateral femurs of rats were harvested for evaluation. All treatment groups increased new bone formation around the surface of titanium rods and push-out force; group Sr-HA showed the strongest effects on new bone formation and biomechanical strength. Additionally, there are significant differences in bone formation and push-out force was observed between groups Zn-HA and Mg-HA. This finding suggests that Zn, Mg, Sr-substituted hydroxyapatite coatings can improve implant osseointegration, and the 10% Sr coating exhibited the best properties for implant osseointegration among the tested coatings in osteoporosis rats.

The effects of combined human parathyroid hormone (1–34) and simvastatin treatment on osseous integration of hydroxyapatite-coated titanium implants in the femur of ovariectomized rats

The effect of human parathyroid hormone 1–34 (PTH) and simvastatin (SIM) alone could promote bone healing in osteoporotic osseous integration of the implant, but there are no reports about the combined use of PTH and SIM for promotion of bone healing around implant in osteoporotic settings still limited. This study aims to investigate effects of PTH+SIM on osseous integration of the implant in OVX rats. Female Sprague-Dawley rats were used for this study. Twelve weeks after bilateral ovariectomy, all animals were randomly divided into four groups: group control; group SIM; group PTH and group PTH+SIM. Afterwards, all OVX rats received hydroxyapatite (HA)-coated titanium rods (external diameter and length are 1.5mm and 20mm) in the femoral medullary canal. Subsequently, the animals from group SIM, group PTH and group PTH+SIM received human parathyroid hormone 1–34 (60μg/kg, three times a week), SIM (5mg/kg daily), or both for 12 weeks. Implants were inserted bilaterally in all animals until death at 12 weeks. The bilateral femurs of rats were harvested for evaluation. All groups increased new bone formation around the surface of titanium rods and push-out force; group PTH+SIM showed the strongest effects on new bone formation and biomechanical strength. Additionally, these are significant difference observed in bone formation and push-out force between groups SIM and PTH. This finding suggests that intermittent administration of PTH or SIM alone has an effect to increase new bone formation on the surface of HA-coated implants in the osteoporotic condition, and the additive effects of combination PTH and SIM on osseous integration of the implant in OVX rats.

Comparison of a Hydroxyapatite-Coated and an Anodic Oxidized Titanium Implant for Experimentally Induced Peri-Implantitis: Macroscopic and Novel Radiographic Evaluations in a Canine Model

This study aimed to compare the response of peri-implant tissue surrounding hydroxyapatite-coated titanium (HA) implants and anodic oxidized titanium (AnO) implants, as well as associated ligature-induced peri-implantitis. The third and fourth premolars (P3, P4) of the mandible were extracted in five beagle dogs. After 2 months, 10 dental implants with different surfaces (HA/AnO) were inserted into the mandible in five beagle dogs. A plaque control program was maintained until the second-stage surgery. Three months after implantation, a healing-cap connection was performed, and silk ligatures were placed in the submarginal position around the neck of the implants to induce peri-implantitis. Macroscopic evaluations including modified plaque index (mPI), modified gingival index (mGI), and probing depth (PD), and radiographic evaluations including dental radiography and multislice computed tomography (MSCT) were conducted for 24 weeks following ligature placement. Bone loss around the implant was evaluated according to the radiolucent area on dental radiographic images and the hyperpermeability area on MSCT images. All macroscopic parameters except PD exhibited a consistent increase for all implants. Over the course of the study, bone loss associated with the HA implant was greater than losses with the AnO implant. Following evaluation of dental radiographs at 20 and 24 weeks after ligature placement, a significant difference was detected between the HA and AnO implants (P < 0.05). The results suggested that the resistance of the HA implant to peri-implantitis was inferior to that of the AnO implant.

Vertical osteoconductivity of sputtered hydroxyapatite-coated mini titanium implants after dura mater elevation: Rabbit calvarial model

This study evaluated the quantity and quality of newly formed vertical bone induced by sputtered hydroxyapatite-coated titanium implants compared with sandblasted acid-etched implants after dura mater elevation. Hydroxyapatite-coated and non-coated implants (n = 20/group) were used and divided equally into two groups. All implants were randomly placed into rabbit calvarial bone (four implants for each animal) emerging from the inferior cortical layer, displacing the dura mater 3 mm below the original bone. Animals were sacrificed at 4 (n = 5) and 8 (n = 5) weeks post-surgery. Vertical bone height and area were analyzed histologically and radiographically below the original bone. Vertical bone formation was observed in both groups. At 4 and 8 weeks, vertical bone height reached a significantly higher level in the hydroxyapatite compared with the non-coated group (p < 0.05). Vertical bone area was significantly larger in the hydroxyapatite compared with the non-coated group at 4 and 8 weeks (p < 0.05). This study indicates that vertical bone formation can be induced by dura mater elevation and sputtered hydroxyapatite coating can enhance vertical bone formation.

Whole body vibration improves osseointegration by up-regulating osteoblastic activity but down-regulating osteoblast-mediated osteoclastogenesis via ERK1/2 pathway

Due to the reduction in bone mass and deterioration in bone microarchitecture, osteoporosis is an important risk factor for impairing implant osseointegration. Recently, low-magnitude, high-frequency (LMHF) vibration (LM: <1×g; HF: 20–90Hz) has been shown to exhibit anabolic, but anti-resorptive effects on skeletal homeostasis. Therefore, we hypothesized that LMHF loading, in terms of whole body vibration (WBV), may improve implant fixation under osteoporotic status. In the in vivo study, WBV treatment (magnitude: 0.3g, frequency: 40Hz, time: 30min/12h, 5days/week) was applied after hydroxyapatite-coated titanium implants were inserted in the bilateral tibiae of ovariectomized rats. The bone mass and the osteospecific gene expressions were measured at 12weeks post implantation. In the in vitro study, the cellular and molecular mechanisms underlying osteoblastic and osteoclastic activities were fully investigated using various experimental assays. Micro-CT examination showed that WBV could enhance osseointegration by improving microstructure parameters surrounding implants. WBV-regulated gene levels in favor of bone formation over resorption may be the reason for the favorable adaptive bone remolding on bone-implant surface. The in vitro study showed that vibration (magnitude: 0.3g, frequency: 40Hz, time: 30min/12h) up-regulated osteoblast differentiation, matrix synthesis and mineralization. However, mechanically regulated osteoclastic activity was mainly through the effect on osteoblastic cells producing osteoclastogenesis-associated key soluble factors, including RANKL and M-CSF. Osteoblasts were therefore the direct target cells during the mechanotransduction process. The ERK1/2 pathway was demonstrated to play an essential role in vibration-induced enhancement of bone formation and decreased bone resorption. Our data suggests that WBV was a helpful non-pharmacological intervention for improving osseointegration under osteoporosis.

Early Healing of Hydroxyapatite‐Coated Implants in Grafted Bone of Zoledronic Acid–Treated Osteoporotic Rabbits

Resorption of grafted bone and delayed osseointegration of implants are main problems associated with alveolar bone augmentation in dental implantology, especially for patients with osteoporosis. The aim of this study is to investigate the early healing response of implants to systemic treatment of zoledronic acid (ZA) in autogenous grafted iliac bone of osteoporotic rabbits. Ovariectomy (OVX) or sham operation was performed in 46 rabbits, and osteoporotic changes were verified in animals receiving OVX 3 months later. The remaining animals were divided into three groups (n = 12): sham, OVX, and OVX with ZA treatment (ZA group). Autogenous iliac bone grafting was performed in bilateral tibiae, and hydroxyapatite-coated titanium implants were simultaneously placed into the grafted bone. The animals were sacrificed 2 and 8 weeks later for examination. At both time points, systemic treatment of ZA efficiently promoted bone healing of implants in grafted bone, and all histologic and microcomputed tomography bone indices, including mineralized bone volume, implant-bone contact ratio, connectivity density, trabecular thickness, and trabecular number, were significantly increased in the ZA group compared with the OVX-only group (P <0.01); implant-bone contact rates in the ZA group were even restored to levels similar to those of sham-operated animals (P >0.05). Furthermore, biomechanical testing demonstrated that removal torque of implants was significantly increased in the ZA group compared with the OVX group (P <0.01). Systemic treatment with ZA could efficiently promote early bone healing of implants in autogenous grafted bone of osteoporotic rabbits by increasing early osseointegration and fixation of implants.

Osteoinductive hydroxyapatite-coated titanium implants

Previous studies have shown that heterotopic induction of bone formation by calcium phosphate-based macroporous constructs is set into motion by the geometry of the implanted substrata, i.e. a sequence of repetitive concavities assembled within the macroporous spaces. The aim of this study was to construct osteoinductive titanium implants that per se, and without the exogenous application of the osteogenic soluble molecular signals of the transforming growth factor-β supergene family, would initiate the induction of bone formation. To generate intrinsically osteoinductive titanium implants for translation in clinical contexts, titanium grade Ti-6A1-4V cylinders of 15 mm in length and 3.85 mm in diameter, with or without concavities, were plasma sprayed with crystalline hydroxyapatite resulting in a uniform layer of 30 μm in thickness. Before coating, experimental titanium implants were prepared with a sequence of 36 repetitive concavities 1600 μm in diameter and 800 μm in depth, spaced a distance of 1000 μm apart. Mandibular molars and premolars were extracted to prepare edentulous mandibular ridges for later implantation. Planar and geometric hydroxyapatite-coated titanium constructs were implanted in the left and right edentulized hemi-mandibles, respectively, after a healing period of 7–8 months, 3 per hemi-mandible. Three planar and three geometric implants were implanted in the left and right tibiae, respectively; additionally, planar and geometric constructs were also inserted in the rectus abdominis muscle. Six animals were euthanized at 30 and 90 days after implantation; one animal had to be euthanized 5 days after surgery and the remaining animal was euthanized 31 months after implantation. Undecalcified longitudinal sections were precision-sawed, ground and polished to 40–60 μm; all sections were stained with a modified Goldner’s trichrome. Undecalcified specimen block preparation was performed using the EXAKT precision cutting and grinding system. Histomorphometric analyses of bone in contact (BIC) showed that on day 30 there was no difference between the geometric vs. planar control implants; on day 90, the ratio of BIC to surface within the geometric implants was greater than on the standard planar implants in both mandibular and tibial sites; 31 months after implantation, selected concavities cut into the geometric implants harvested from the rectus abdominis muscle showed the spontaneous induction of bone formation with mineralized bone surfaced by osteoid seams. These data in non-human primates indicate that geometrically-constructed plasma-sprayed titanium implants are per se osteogenic, the concavities providing a unique microenvironment to initiate bone differentiation by induction.

The effect of surface immobilized bisphosphonates on the fixation of hydroxyapatite-coated titanium implants in ovariectomized rats

Immobilized bisphosphonates (BPs) have been introduced to improve implant fixation, however, no information could be found about the efficiency of this approach in osteoporotic bone. This study was designed to evaluate the bone response to surface immobilized BPs on implants inserted in tibiae of ovariectomized (OVX) rats. Three months after bilateral ovariectomy, 40 rats were randomly assigned into four groups for implantation of hydroxyapatite-coated titanium implants with or without immobilized BPs: (1) control group (without BP treatments); (2) pamidronate (PAM) group (1 mg/ml of PAM immersing); (3) ibandronate group (1 mg/ml of ibandronate immersing); and (4) zoledronic acid (ZOL) group (1 mg/ml of ZOL immersing). After implantation periods of 3 months, the peri-implant–bone density, trabecular microstructure, bone–implant interface and mechanical fixation of implants were evaluated by dual energy X-ray absorptiometry, micro-computed tomography, histology and push-out test. We found that three BPs triggered pronounced bone–implant integration and early bone formation around implants in OVX rats, with a rank order of ZOL > ibandronate > PAM. These results provide new evidence that immobilized BPs have positive effects on implant fixation in osteoporotic bone, in addition to their well-documented potency to inhibit implant loosening in normal bone.

The bisphosphonate ibandronate accelerates osseointegration of hydroxyapatite-coated cementless implants in an animal model

BackgroundThere is evidence that bisphosphonates can improve fixation of cementless metal implants by enhancing the extent of osseointegration. The current preclinical study examined whether the nitrogen-containing bisphosphonate ibandronate can accelerate this process, resulting in early achievement of secondary stability and sealing of the bone–implant interface to prevent wear debris migration. MethodsThe study was conducted on 88 female Sprague-Dawley rats in which uncoated titanium and hydroxyapatite-coated titanium implants were surgically inserted into the medullary canal of each femur. The animals were randomly assigned to receive subcutaneous treatment with 1.0, 2.5, or 5.0 μg/kg per day ibandronate or saline solution as a control. The extent of osseointegration expressed by the osseointe-grated implant surface was quantified by histomorphometry at eleven time points during the study period. To determine the time course of osseointegration, the data were expressed using third-order polynomial regression analysis. ResultsFor hydroxyapatite-coated implants, the highest dose of ibandronate (5 μg) reduced the time for a sufficient implant fixation of 60% osseointegrated implant surface to 18 days compared to 38 days in the control group. This reduction of 20 days (52.6%) represents a halving in the time required for sufficient osseointegration of the implant. For hydroxyapatite-coated implants and low-dose ibandronate application (1 μg, 2.5 μg) and for uncoated titanium implants, acceleration of osseointegration was not observed in any of the study arms. ConclusionContinuous treatment with 5 μg/kg per day iban-dronate is potent in accelerating osseointegration of hydroxy-apatite-coated implants. As a result, improved early secondary stability and prevention of wear debris migration by the sealing of the implant–bone interface can be expected, therefore prolonging the long-term survival of the implant.

Bacterial Plaque Colonization Around Dental Implant Surfaces

To examine the distribution of bacteria into the internal and external surfaces of failed implants using histologic analysis. There were 10 failed pure titanium and 5 failed hydroxyapatite-coated titanium implants consecutively removed various years after their placement. Criteria for fixture removal were peri-implant radiolucency and clinical mobility. The mobile fixtures were retrieved with the patients under local anesthesia. Fixtures were removed maintaining the abutments with the aim to observe the bacterial infiltration at the level of abutment/implant interface and on the implant surface. A thin radiolucent space was always present around all the failed implants. The abutments screws were tightly secured in all clinical cases. The bacterial cells were composed of cocci and filaments, which were adherent to the implant surface with an orientation perpendicular to the long axis of the implant. All the specimens included in this study showed bacteria at the level of implant/abutment interface. Histologic analysis at the level of abutment/implant interface in 2-stage implants identified heavy bacterial colonization. These findings appear to support those studies showing bacteria penetration at the level of the micro-gap, which can legitimate the hypothesis that the micro-gap at the bone level could present a risk for bone loss caused by bacterial colonization.

Osseointegration of Cementless Implants with Different Bisphosphonate Regimens

Some evidence suggests a daily dose of bisphosphonates improves fixation of cementless metal implants by enhancing osseointegration. Because the necessity of daily administration may result in suboptimal adherence to therapy, single- dose administration is desirable. We examined whether a dose-equivalent single injection of the nitrogen-containing bisphosphonate ibandronate is as effective as a daily injection in improving the osseointegrated surface and enhancing periprosthetic bone mineralization (bone volume to tissue volume) of cementless metal implants. Uncoated titanium and hydroxyapatite-coated titanium implants were surgically inserted into the femoral medullary canal of 55 female Sprague Dawley rats. The animals were randomly assigned subcutaneous treatments with 25 microg/kg body weight ibandronate per day, a dose-equivalent single injection of 28 x 25 microg/kg body weight, or saline solution for control. Histomorphometric evaluation revealed an enhanced osseointegrated surface for hydroxyapatite-coated implants in both treatment groups, but only for daily injections for uncoated titanium implants. Bone volume to tissue volume was improved in both treatment groups. Our results suggest that an equivalent-dose single injection of ibandronate is as effective as a daily dose in improving osseointegration and stabilization of hydroxyapatite-coated titanium implants in this rat model.