Ahmed Ballo

Biomineralized strontium-substituted apatite/titanium dioxide coating on titanium surfaces.

Bone mineral is a multi-substituted calcium phosphate. One of these ion substitutions, strontium, has been proven to increase bone strength and decrease bone resorption. Biomimetics is a potential way to prepare surfaces that provide a favorable bone tissue response, thus enhancing the fixation between bone and implants. Here we prepared double-layered strontium-substituted apatite and titanium dioxide coatings on titanium substrates via mimicking bone mineralization. Morphology, crystallinity, surface chemistry and composition of Sr-substituted coatings formed via biomimetic coating deposition on crystalline titanium oxide substrates were studied as functions of soaking temperature and time in phosphate buffer solutions with different Sr ion concentration. The morphology of the biomimetic apatite changed from plate-like for the pure HA to sphere-like for the Sr ion substituted. Surface analysis results showed that 10-33% of Ca ions in the apatite have been substituted by Sr ions, and that the Sr ions were chemically bonded with apatite and successfully incorporated into the structure of apatite.

Nanostructured model implants for in vivo studies: influence of well-defined nanotopography on de novo bone formation on titanium implants.

An implantable model system was developed to investigate the effects of nanoscale surface properties on the osseointegration of titanium implants in rat tibia. Topographical nanostructures with a well-defined shape (semispherical protrusions) and variable size (60 nm, 120 nm and 220 nm) were produced by colloidal lithography on the machined implants. Furthermore, the implants were sputter-coated with titanium to ensure a uniform surface chemical composition. The histological evaluation of bone around the implants at 7 days and 28 days after implantation was performed on the ground sections using optical and scanning electron microscopy. Differences between groups were found mainly in the new bone formation process in the endosteal and marrow bone compartments after 28 days of implantation. Implant surfaces with 60 nm features demonstrated significantly higher bone-implant contact (BIC, 76%) compared with the 120 nm (45%) and control (57%) surfaces. This effect was correlated to the higher density and curvature of the 60 nm protrusions. Within the developed model system, nanoscale protrusions could be applied and systematically varied in size in the presence of microscale background roughness on complex screw-shaped implants. Moreover, the model can be adapted for the systematic variation of surface nanofeature density and chemistry, which opens up new possibilities for in vivo studies of various nanoscale surface-bone interactions.

Bone tissue reactions to biomimetic ion-substituted apatite surfaces on titanium implants

The aim of this study was to evaluate the bone tissue response to strontium- and silicon-substituted apatite (Sr-HA and Si-HA) modified titanium (Ti) implants. Sr-HA, Si-HA and HA were grown on thermally oxidized Ti implants by a biomimetic process. Oxidized implants were used as controls. Surface properties, i.e. chemical composition, surface thickness, morphology/pore characteristics, crystal structure and roughness, were characterized with various analytical techniques. The implants were inserted in rat tibiae and block biopsies were prepared for histology, histomorphometry and scanning electron microscopy analysis. Histologically, new bone formed on all implant surfaces. The bone was deposited directly onto the Sr-HA and Si-HA implants without any intervening soft tissue. The statistical analysis showed significant higher amount of bone–implant contact (BIC) for the Si-doped HA modification (P = 0.030), whereas significant higher bone area (BA) for the Sr-doped HA modification (P = 0.034), when compared with the non-doped HA modification. The differences were most pronounced at the early time point. The healing time had a significant impact for both BA and BIC (P < 0.001). The present results show that biomimetically prepared Si-HA and Sr-HA on Ti implants provided bioactivity and promoted early bone formation.

The role of well-defined nanotopography of titanium implants on osseointegration: cellular and molecular events in vivo

Purpose Mechanisms governing the cellular interactions with well-defined nanotopography are not well described in vivo. This is partly due to the difficulty in isolating a particular effect of nanotopography from other surface properties. This study employed colloidal lithography for nanofabrication on titanium implants in combination with an in vivo sampling procedure and different analytical techniques. The aim was to elucidate the effect of well-defined nanotopography on the molecular, cellular, and structural events of osseointegration. Materials and methods Titanium implants were nanopatterned (Nano) with semispherical protrusions using colloidal lithography. Implants, with and without nanotopography, were implanted in rat tibia and retrieved after 3, 6, and 28 days. Retrieved implants were evaluated using quantitative polymerase chain reaction, histology, immunohistochemistry, and energy dispersive X-ray spectroscopy (EDS). Results Surface characterization showed that the nanotopography was well defined in terms of shape (semispherical), size (79±6 nm), and distribution (31±2 particles/µm2). EDS showed similar levels of titanium, oxygen, and carbon for test and control implants, confirming similar chemistry. The molecular analysis of the retrieved implants revealed that the expression levels of the inflammatory cytokine, TNF-α, and the osteoclastic marker, CatK, were reduced in cells adherent to the Nano implants. This was consistent with the observation of less CD163-positive macrophages in the tissue surrounding the Nano implant. Furthermore, periostin immunostaining was frequently detected around the Nano implant, indicating higher osteogenic activity. This was supported by the EDS analysis of the retrieved implants showing higher content of calcium and phosphate on the Nano implants. Conclusion The results show that Nano implants elicit less periimplant macrophage infiltration and downregulate the early expression of inflammatory (TNF-α) and osteoclastic (CatK) genes. Immunostaining and elemental analyses show higher osteogenic activity at the Nano implant. It is concluded that an implant with the present range of well-defined nanocues attenuates the inflammatory response while enhancing mineralization during osseointegration.

Mesoporous titanium dioxide coating for metallic implants.

A bioactive mesoporous titanium dioxide (MT) coating for surface drug delivery has been investigated to develop a multifunctional implant coating, offering quick bone bonding and biological stability. An evaporation induced self-assembly (EISA) method was used to prepare a mesoporous titanium dioxide coating of the anatase phase with BET surface area of 172 m(2)/g and average pore diameter of 4.3 nm. Adhesion tests using the scratch method and an in situ screw-in/screw-out technique confirm that the MT coating bonds tightly with the metallic substrate, even after removal from bone. Because of its high surface area, the bioactivity of the MT coating is much better than that of a dense TiO(2) coating of the same composition. Quick formation of hydroxyapatite (HA) in vitro can be related to enhance bonding with bone. The uptake of antibiotics by the MT coating reached 13.4 mg/cm(3) within a 24 h loading process. A sustained release behavior has been obtained with a weak initial burst. By using Cephalothin as a model drug, drug loaded MT coating exhibits a sufficient antibacterial effect on the material surface, and within millimeters from material surface, against E.coli. Additionally, the coated and drug loaded surfaces showed no cytotoxic effect on cell cultures of the osteoblastic cell line MG-63. In conclusion, this study describes a novel, biocompatiblemesoporous implant coating, which has the ability to induce HA formation and could be used as a surface drug-delivery system.

Dental Implant Surfaces – Physicochemical Properties, Biological Performance, and Trends

Pure titanium and titanium alloys are well established standard materials in dental implants because of their favorable combination of mechanical strength, chemical stability, and biocompatibility (Brunette et al., 2001). Integration of titanium implants with the surrounding bone is critical for successful bone regeneration and healing of dental implant. The concept of osseointegration was discovered by Branemark and his co-worker and, has had a dramatic influence on clinical treatment of oral implants. The first generation of successfully used clinical titanium implants, which were machined with a smooth surface texture, now approach 50 years in clinical use. Since then, implant surfaces have long been recognized to play an important role in molecular interactions, cellular response and osseointegration, and scientists all over the world have developed the second generation implants with surfaces which can accelerate and improve implant osseointegration. These second generation of clinically used implants underwent mechanical blasting coupled or not, with acid etch, bioactive coatings, anodized and, more recently, laser modified surfaces. (Cochran et al., 1998; Jansen et al., 1993; Palmquist et al., 2010; Branemark et al., 2010 ). These implants have been extensively documented in vivo, including long-term clinical studies and experimental histological and biomechanical evaluation in animal models. For more knowledge in clinical results of commercially available implants the reader is referred to the following literature (Esposito et al., 2005; Esposito et al., 2003; Albrektsson & Wennerberg, 2004b). The main objective for the development of implant surface modifications is to promote osseointegration, with faster and stronger bone formation. This will likely confer better stability during the healing process, which, preferentially, will improve the clinical performance in the area of poor bone quality and quantity. Furthermore, such promotion may, in turn, accelerate the bone healing and thereby allowing immediate or early loading protocols. Recently growing micro and nanotechnology is rapidly advancing surface engineering in implant dentistry. Such advances in surface engineering technologies have resulted in more