A Bioinspired Orthopedic Biomaterial with Tunable Mechanical Properties Based on Sintered Titanium Fibers.

Inadequate mechanical compliance of orthopedic implants can result in excessive strain of the bone interface, and ultimately, aseptic loosening. It is hypothesized that a fiber-based biometal with adjustable anisotropic mechanical properties can reduce interface strain, facilitate continuous remodeling, and improve implant survival under complex loads. The biometal is based on strategically layered sintered titanium fibers. Six different topologies are manufactured. Specimens are tested under compression in three orthogonal axes under 3-point bending and torsion until failure. Biocompatibility testing involves murine osteoblasts. Osseointegration is investigated by micro-computed tomography and histomorphometry after implantation in a metaphyseal trepanation model in sheep. The material demonstrates compressive yield strengths of up to 50 MPa and anisotropy correlating closely with fiber layout. Samples with 75% porosity are both stronger and stiffer than those with 85% porosity. The highest bending modulus is found in samples with parallel fiber orientation, while the highest shear modulus is found in cross-ply layouts. Cell metabolism and morphology indicate uncompromised biocompatibility. Implants demonstrate robust circumferential osseointegration in vivo after 8 weeks. The biometal introduced in this study demonstrates anisotropic mechanical properties similar to bone, and excellent osteoconductivity and feasibility as an orthopedic implant material.

Molybdenum as a Potential Biocompatible and Resorbable Material for Osteosynthesis in Craniomaxillofacial Surgery-An In Vitro Study.

Titanium and stainless steel are commonly known as osteosynthesis materials with high strength and good biocompatibility. However, they have the big disadvantage that a second operation for hardware removal is necessary. Although resorbable systems made of polymers or magnesium are increasingly used, they show some severe adverse foreign body reactions or unsatisfying degradation behavior. Therefore, we started to investigate molybdenum as a potential new biodegradable material for osteosynthesis in craniomaxillofacial surgery. To characterize molybdenum as a biocompatible material, we performed in vitro assays in accordance with ISO Norm 10993-5. In four different experimental setups, we showed that pure molybdenum and molybdenum rhenium alloys do not lead to cytotoxicity in human and mouse fibroblasts. We also examined the degradation behavior of molybdenum by carrying out long-term immersion tests (up to 6 months) with molybdenum sheet metal. We showed that molybdenum has sufficient mechanical stability over at least 6 months for implants on the one hand and is subject to very uniform degradation on the other. The results of our experiments are very promising for the development of new resorbable osteosynthesis materials for craniomaxillofacial surgery based on molybdenum.

Biocompatibility and Degradation Behavior of Molybdenum in an In Vivo Rat Model.

The biocompatibility and degradation behavior of pure molybdenum (Mo) as a bioresorbable metallic material (BMM) for implant applications were investigated. In vitro degradation of a commercially available Mo wire (ø250 µm) was examined after immersion in modified Kokubo's SBF for 28 days at 37 °C and pH 7.4. For assessment of in vivo degradation, the Mo wire was implanted into the abdominal aorta of female Wistar rats for 3, 6 and 12 months. Microstructure and corrosion behavior were analyzed by means of SEM/EDX analysis. After explantation, Mo levels in serum, urine, aortic vessel wall and organs were investigated via ICP-OES analysis. Furthermore, histological analyses of the liver, kidneys, spleen, brain and lungs were performed, as well as blood count and differentiation by FACS analysis. Levels of the C-reactive protein were measured in blood plasma of all the animals. In vitro and in vivo degradation behavior was very similar, with formation of uniform, non-passivating and dissolving product layers without occurrence of a localized corrosion attack. The in vitro degradation rate was 101.6 µg/(cm2·d) which corresponds to 33.6 µm/y after 28 days. The in vivo degradation rates of 12, 33 and 36 µg/(cm2·d) were observed after 3, 6 and 12 months for the samples properly implanted in the aortic vessel wall. This corresponds with a degradation rate of 13.5 µm/y for the 12-month cohort. However, the magnitude of degradation strongly depended on the implant site, with the wires incorporated into the vessel wall showing the most severe degradation. Degradation of the implanted Mo wire neither induced an increase in serum or urine Mo levels nor were elevated Mo levels found in the liver and kidneys compared with the respective controls. Only in the direct vicinity of the implant in the aortic vessel wall, a significant amount of Mo was found, which, however, was far below the amounts to be expected from degrading wires. No abnormalities were detected for all timepoints in histological and blood analyses compared to the control group. The C-reactive protein levels were similar between all the groups, indicating no inflammation processes. These findings suggest that dissolved Mo from a degrading implant is physiologically transported and excreted. Furthermore, radiographic and µCT analyses revealed excellent radiopacity of Mo in tissues. These findings and the unique combination with its extraordinary mechanical properties make Mo an interesting alternative for established BMMs.

Local and systemic inflammation after implantation of a novel iron based porous degradable bone replacement material in sheep model.

Despite the high potential of healthy bone to regenerate, the reconstruction of large bone defects remains a challenge. Due to the lack of mechanical stability of existing bone substitutes, recently developed degradable metallic alloys are an interesting alternative providing higher load-bearing capabilities. Degradable iron-based alloys therefore might be an attractive innovation. To test the suitability of a newly-designed iron-based alloy for such applications, an animal experiment was performed. Porous iron-based degradable implants with two different densities and a control group were tested. The implants were positioned in the proximal tibia of Merino sheep. Over a period of 6 and 12 months, blood and histological parameters were monitored for signs of inflammation and degradation. In the histological evaluation of the implants` environment we found degraded alloy particles, but no inflammatory reaction. Iron particles were also found within the popliteal lymph nodes on both sides. The serum blood levels of phosphorus, iron and ferritin in the long term groups were elevated. Other parameters did not show any changes. Iron-based degradable porous bone replacement implants showed a good biocompatibility in this experiment. For a clinical application, however, the rate of degradation would have to be significantly increased. Biocompatibility would then have to be re-evaluated.

Development of a novel biodegradable porous iron-based implant for bone replacement.

Bone replacement and osteosynthesis require materials which can at least temporarily bear high mechanical loads. Ideally, these materials would eventually degrade and would be replaced by bone deposited from the host organism. To date several metals, notably iron and iron-based alloys have been identified as suitable materials because they combine high strength at medium corrosion rates. However, currently, these materials do not degrade within an appropriate amount of time. Therefore, the aim of the present study is the development of an iron-based degradable sponge-like (i.e. cellular) implant for bone replacement with biomechanically tailored properties. We used a metal powder sintering approach to manufacture a cylindrical cellular implant which in addition contains phosphor as an alloying element. No corrosion inhibiting effects of phosphorus have been found, the degradation rate was not altered. Implant prototypes were tested in an animal model. Bone reaction was investigated at the bone-implant-interface and inside the cellular spaces of the implant. Newly formed bone was growing into the cellular spaces of the implant after 12 months. Signs of implant degradation were detected but after 12 months, no complete degradation could be observed. In conclusion, iron-based open-porous cellular biomaterials seem promising candidates for the development of self-degrading and high load bearing bone replacement materials.

Molybdenum - A biodegradable implant material for structural applications?

Molybdenum as a potentially new biodegradable material was investigated. Degradation behavior of commercially high purity molybdenum was observed in simulated physiological salt solutions (Kokubo's SBF with/without TRIS-HCl, Cu2+ addition and 0.9% NaCl solution). Potentiodynamic polarization, immersion mass loss and ion concentration measurements paired with REM/EDX analysis reveal gradual dissolution of molybdenum in the proper order of magnitude for stent application, associated with formation of thin, non-passivating corrosion products. The underlying corrosion mechanism is discussed as well as a comparison to literature data. However, formation of calcium phosphates (CaP) in SBF significantly decreases corrosion rates. In-situ polarization was found to be a potential way for overcoming this problem and simultaneously enhancing corrosion above the benchmark for a degradable stent material. STATEMENT OF SIGNIFICANCE: Biodegradable metals have the potential to overcome severe complications common to orthopedic and cardio-vascular implants. However, the need for a material with moderate and predictable degradation, high strength and toughness as well as MRI suitability must be satisfied. Molybdenum as potential new biodegradable material may just fulfill these requirements. An overall positive picture of molybdenum as an interesting alternative to recently discussed metallic biodegradable materials can be concluded from the herein presented results and from literature data, showing directions for future research on the topic.

Strontium and bisphosphonate coated iron foam scaffolds for osteoporotic fracture defect healing.

The purpose of this work was to investigate new bone formation in macroporous iron foams coated with strontium (FeSr) or bisphosphonate (FeBiP) compared to plain iron foam (Fe) and empty defect in a critical size metaphyseal bone defect model in ovariectomized rats. 60 female rats were subjected to bilateral ovariectomy and multi-deficient diet for 3 months. A 4 mm wedge shaped metaphyseal osteotomy was created, fixed with a mini-plate and subsequently filled with Fe, FeSr, FeBiP or left empty. After 6 weeks, µCt analysis revealed a statistically significant increased bone formation at the implant interface in FeSr compared to FeBiP (p = 0.035) and Fe (p = 0.002), respectively. Increased mineralized tissue was also seen within the pores in FeSr (p = 0.023) compared to Fe. Histomorphometry revealed significantly increased bone formation at the implant interface in FeSr (p < 0.001) and FeBiP (p = 0.006) compared to plain Fe with increased osteoblast and decreased osteoclast activity in combination with increased BMP2 and decreased RANKL/OPG in immunohistochemistry. ToF-SIMS analysis showed overlapping Ca signals with Fe for both FeSr and FeBiP thereby indicating tissue in-growth into the scaffolds. In conclusion, iron foam with strontium or bisphosphonate coating are of further interest in metaphyseal fracture defects in osteopenic bone.