Ole Zoffmann Andersen

Accelerated bone ingrowth by local delivery of strontium from surface functionalized titanium implants

Studies have indicated systemic treatment with strontium (Sr) as a potential route to increase bone quality and formation around osseointegrating implants. However, adverse effects are linked to such treatment. In this study we present a surface modification method designed for sustained local release of Sr from implants. The four groups used were prepared by a magnetron co-sputtering process and selected on the basis of Sr release data. The composition, morphology and mechanical stability of the coatings were analyzed and the Sr release profiles were investigated in vitro by washout experiments. Mesenchymal stem cells were cultured on the different coatings to evaluate potential cytotoxic effects and the effect on cellular proliferation. No indication of toxicity was found. A rodent study demonstrated a significant increase in direct bone-to-implant contact and peri-implant bone volume, for several of the groups, four weeks after implantation when compared to a Grade 4 titanium reference group. Median values of bone-to-implant contact and new bone formation was found to be 19% and 53%, respectively, for the best group compared to 0% for both parameters with respect to the Grade 4 titanium reference. The results indicate that this method may have applications within the orthopedic and dental industry.

Enhanced osseointegration of endosseous implants by predictable sustained release properties of strontium

UNLABELLED Studies have shown that strontium (Sr) incorporated into surfaces may enhance osseointegration. Thus, we suggested that a sustained Sr release from implant surfaces could improve bone healing. This study verifies and further investigates the effect of a novel Ti-Sr-O functionalized implant surface prepared from a magnetron co-sputtering platform with a continuous release of Sr. MATERIALS AND METHODS Four experimental Ti-Sr-O groups, which differed from each other in Sr contents and pre-wash procedures, were tested. Implants were prepared with a Ti-Sr-O coating by means of magnetron co-sputtering and compared to Grade 4 titanium. Composition, morphology and mechanical stability were analyzed; Sr-release data were gained from in vitro washout experiments. In vivo investigations were carried out in a rat model and analyzed histologically regarding bone-to-implant contact and new bone formation 30 days after implantation. RESULTS Structural differences were detected between the two basis Ti-Sr-O coatings with 6.7 at.% and 8.9 at.% Sr, respectively. Different release profiles were observed with 8.9 at.% Sr coating exhibiting the highest long-term release of Sr. Median values of new bone formation and bone-to-implant contact was found to be 60.1% and 91.6%, respectively, for the best group compared to 16.6% and 70.6% for the Grade 4 titanium reference. The increase in new bone formation was found to correlate with the amount of Sr released in vitro. CONCLUSION The results show that sputtered Ti-Sr-O coatings with sustained release of Sr may improve osseointegration, and could thus have impact on practical applications for medical implants.

Effect of strontium surface-functionalized implants on early and late osseointegration: A histological, spectrometric and tomographic evaluation

Numerous in vivo, in vitro and clinical studies report on beneficial effects of strontium with respect to increased bone growth. Based on this knowledge the aim of this study was to evaluate early and late osseointegration stages of functionalized titanium implants showing sustained release of strontium (Sr) and further investigate its potential systemic effect. Strontium functionalized (Ti-Sr-O) and Grade 4 (Control) titanium implants were inserted in the femoral condyle of New Zealand White rabbits. The Ti-Sr-O coating was characterized using Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray Spectrometry (EDX) for structure, coating thickness and chemical composition. Inductively Coupled Plasma Atomic Emission Spectrometry (ICP-AES) was used to evaluate released strontium in vitro while Atomic Absorption Spectrometry (AAS) was utilized to monitor serum levels of strontium and calcium. Additionally, histological and tomographic analysis of bone-to-implant contact (BIC%) and bone formation (BF%) was performed, following implantation periods of two or twelve weeks, respectively. Median values for BIC% for Ti-Sr-O revealed significant differences within the two- and twelve-week observation periods, while exceeding BF% was discovered especially after twelve weeks when performing the histological evaluation. The results from the micro-computed tomography (µ-CT) showed no significant differences, when comparing the experimental groups. AAS measurements did not indicate a systemic effect by the local strontium release. Within the limitations of the study, it was shown that a Ti-Sr-O coating with sustained release characteristics of strontium, accelerates bone apposition and represents a potential potent surface modification for endosseous medical implant devices. STATEMENT OF SIGNIFICANCE This study presents first data with respect to early and late in vivo response on a strontium functionalized titanium surface comprising a nanotopography manufactured by a magnetron sputtering process. We investigated different osseointegration stages of screw-shaped implants with dental implant geometries in a rabbit femur model observing beneficial effects of the functionalized surface on bone-to-implant contact and bone formation caused by tailored release of the bone anabolic strontium. Histomorphometrical data revealed that a functionalized titanium surface with controlled liberation of strontium accelerates osseointegration while spectrometry measurements did not indicate a potential systemic effect of this osteoinductive agent and could thus have impact on modifications of medical implant devices.

Bone regenerating effect of surface-functionalized titanium implants with sustained-release characteristics of strontium in ovariectomized rats

Since strontium (Sr) is known for its anabolic and anticatabolic effect on bone, research has been focused on its potential impact on osseointegration. The objective of this study was to investigate the performance of nanotopographic implants with a Sr-functionalized titanium (Ti) coating (Ti–Sr–O) with respect to osseointegration in osteoporotic bone. The trial was designed to examine the effect of sustained-release characteristics of Sr in poor-quality bone. Three Ti–Sr–O groups, which differed from each other in coating thickness, Sr contents, and Sr release, were examined. These were prepared by a magnetron sputtering process and compared to uncoated grade 4 Ti. Composition, morphology, and mechanical stability of the coatings were analyzed, and Sr release data were gained from in vitro washout experiments. In vivo investigation was carried out in an osteoporotic rat model and analyzed histologically, 6 weeks and 12 weeks after implantation. Median values of bone-to-implant contact and new bone formation after 6 weeks were found to be 84.7% and 54.9% (best performing Sr group) as compared to 65.2% and 23.8% (grade 4 Ti reference), respectively. The 12-week observation period revealed 84.3% and 56.5% (best performing Sr group) and 81.3% and 39.4% (grade 4 Ti reference), respectively, for the same measurements. The increase in new bone formation was found to correlate with the amount of Sr released in vitro. The results indicate that sputtered nanostructured Ti–Sr–O coatings showed sustained release of Sr and accelerate osseointegration even in poor-quality bone, and thus, may have impact on practical applications for medical implants.

A comparative in vivo study of strontium-functionalized and SLActive™ implant surfaces in early bone healing

Purpose Studies have shown that strontium-doped medical applications benefit bone metabolism leading to improved bone healing and osseointegration. Based on this knowledge, the aim of the study was to evaluate the performance of an implant surface, functionalized by a physical vapor deposition (PVD) coating (Ti-Sr-O), designed to yield predictable release of strontium. The Ti-Sr-O functionalized surface is compared to a routinely used, commercially available surface (SLActive™) with respect to bone-to-implant contact (BIC%) and new bone formation (BF%) in two defined regions of interest (ROI-I and ROI-II, respectively). Materials and methods: Ti-Sr-O functionalized, SLActive, and Grade 4 titanium implants were inserted in the femoral condyle of adult male New Zealand White rabbits. The PVD magnetron-sputtered Ti-Sr-O surface coating was characterized using scanning electron microscopy (SEM) for morphology and coating thickness. Strontium release and mechanical stability of the coating, under simulated insertion conditions, were evaluated. Furthermore, histomorphometrical BIC and BF were carried out 2 weeks after insertion. Results Histomorphometry revealed increased bone formation of Ti-Sr-O with significant differences compared to SLActive and Grade 4 titanium in both regions of interest, ROI-I and ROI-II, at 0–250 µm and 250–500 µm distance from the implant surfaces. Analogous results of bone-to-implant contact were observed for the two modified surfaces. Conclusion The results show that a nanopatterned Ti-Sr-O functionalized titanium surface, with sustained release of strontium, increases peri-implant bone volume and could potentially contribute to enhancement of bone anchorage of osseointegrated implants.

Guided Cellular Responses by Surface Cues for Nanomedicine Applications

Using surface cues to guide and ultimately control cellular responses is of paramount importance in numerous biomedical applications. Since cells react on feature sizes both on the micro and nanometer scale, these length scales are crucial parameters when designing new materials for applications in medicine e.g. for tissue engineering and drug delivery. Thus, variation of the features at the nanometer length scale is an integral part of nanomedicine research and development. In this chapter the interaction between biological systems and artificial materials will be addressed in general with focus on simplified model systems where only one or a few parameters are varied at two-dimensional (2D) surfaces. At first biomolecular adsorption/immobilization on surfaces will be addressed followed by a discussion of approaches to synthesize functionalized surfaces and the influence of such surfaces on cellular response. Some of the key parameters, which will be discussed in more detail, are topography, chemistry, and elastic modulus of the substrate. Even though there is a vast amount of published data it will become clear that there is still not a detailed understanding of the influence of these parameters on biosystems at the cellular level. Obviously, the degree of complexity increases when several of the surface cues are combined. The challenges in understanding the cellular responses in detail in real systems with the simultaneous variation of multiple parameters leads to the introduction of the field of high throughput screening of biomaterials.