Pre-clinical testing of human size magnesium implants in miniature pigs: Implant degradation and bone fracture healing at multiple implantation sites.

Two miniature pig models to assess safety and performance of degradable osteosynthesis implants are presented. Both models provide multiple implantation sites with human size implants. In the first model, different types of magnesium plates and screws for fracture fixation were used to study local and systemic safety aspects in 14 Göttingen minipigs. Implant degradation, gas release and accumulation of alloying elements in organs were assessed for non-coated and plasmaelectrolytic coated magnesium implants and compared to the titanium reference. The observed implant degradation was mostly uniform and did not seem to depend on the implantation site and implant condition. The coating was effective in delaying initial gas release and degradation. No rare earth alloying elements could be detected in local lymph nodes, kidneys, livers or spleens. In the second model with Göttingen und Yucatan minipigs, full osteotomies were inflicted to four different anatomical sites and treated with magnesium plates and screws to assess fracture healing performance. Two Göttingen pilot minipigs showed promising results including a mandible osteosynthesis which healed within 6 weeks. The subsequent study was compromised by the more massive jaws of the used Yucatan minipigs. Three out of seven animals had to be sacrificed within two months as the stability of magnesium and titanium reference implants in the mandible was surpassed. In conclusion, the resorbable magnesium implants showed promising in vivo properties. For the analysis of human standard sized implants under full chewing load conditions, lighter Göttingen minipigs were more suitable than heavier Yucatan minipigs.

Effect of a plasmaelectrolytic coating on the strength retention of in vivo and in vitro degraded magnesium implants.

The strength decrease in magnesium implants was studied in vitro and in vivo, with and without a protective plasmaelectrolytic coating. In vivo, degradation was examined by implanting rectangular plates on top of the nasal bone of miniature pigs. The presence of gas pockets in the soft tissue surrounding the implants was evaluated with intermediate X-rays and computed X-ray tomography scans before euthanasia. After 12 and 24 weeks of in vivo degradation, the large rectangular plates were removed and mechanically tested in three-point bending. In vitro, identical plates were immersed in simulated body fluid for 4, 8 and 12 weeks. In vitro and in vivo results showed that onset of gas release can be delayed by the plasmaelectrolytic coating. Mass loss and strength retention during in vivo degradation is about four times slower than during in vitro degradation for the chosen test conditions. Despite the slow degradation of the investigated WE43 alloy, the occurrence of gas pockets could not be completely avoided. Nevertheless, uniformity of degradation and reliable strength retention make this alloy a prime candidate for the use of magnesium in cranio-maxillofacial surgery.

Characterization methods of bone-implant-interfaces of bioresorbable and titanium implants by fracture mechanical means.

Bioresorbable materials for implants have become increasingly researched over the last years. The bone-implant-interfaces of three different implant materials, namely a new bioresorbable magnesium alloy, a new self-reinforced polymer implant and a conventional titanium alloy, were tested using various methods: push-out tests, SEM and EDX analyses as well as surface analyses based on stereoscopic 3D pictures were conducted. The fracture energy is proposed as a very significant reference value for characterizing the mechanical performance of a bone-implant system. By using a video-extensometer system instead of, as is commonly done, tracking the movement of the crosshead in the push-out tests, the accuracy of measurement could be increased.

Characterization of the deformation behavior of intermediate porosity interconnected Ti foams using micro-computed tomography and direct finite element modeling.

Under load-bearing conditions metal-based foam scaffolds are currently the preferred choice as bone/cartilage implants. In this study X-ray micro-computed tomography was used to discretize the three-dimensional structure of a commercial titanium foam used in spinal fusion devices. Direct finite element modeling, continuum micromechanics and analytical models of the foam were employed to characterize the elasto-plastic deformation behavior. These results were validated against experimental measurements, including ultrasound and monotonic and interrupted compression testing. Interrupted compression tests demonstrated localized collapse of pores unfavorably oriented with respect to the loading direction at many isolated locations, unlike the Ashby model, in which pores collapse row by row. A principal component analysis technique was developed to quantify the pore anisotropy which was then related to the yield stress anisotropy, indicating which isolated pores will collapse first. The Gibson-Ashby model was extended to incorporate this anisotropy by considering an orthorhombic, rather than a tetragonal, unit cell. It is worth noting that the natural bone is highly anisotropic and there is a need to develop and characterize anisotropic implants that mimic bone characteristics.

Characterization of the structure and permeability of titanium foams for spinal fusion devices.

Titanium foams produced via the space-holder method are used for spinal fusion devices since their combination of an open-cell structure and bone-like mechanical properties promises potentially excellent bone ingrowth. Earlier studies have indicated that the size of the pores and interconnects must be greater than 100microm for effective bone ingrowth and vascularization. Hence, the quantification of the pore and interconnect size is required for efficient scaffold design. In this study, microcomputed tomography (microCT) was used to obtain the three-dimensional (3D) structure of Ti foams with three levels of porosity (51%, 65% and 78%). Novel algorithms were then applied to quantify both the pore and interconnect size of Ti foams as a function of porosity. All foams possessed a modal pore and interconnect size in excess of 300microm, satisfying the requirement of being greater than 100microm. The pore and interconnect size also dominates the flow properties or permeability of open-cell structures. Therefore, the microCT data was also used to generate a mesh for computational fluid dynamics analysis to predict the permeability. The calculated permeability (117-163x10(-12)m(2) depending on direction) for the Ti foams with 65% porosity was first validated against experimental measurements (98-163x10(-12)m(2)) and then compared to prior authors' measurements in healthy cancellous bovine bone (233-465x10(-12)m(2)). The close match among all the permeability values proves the suitability of the material for biomedical skeletal-implant applications.

Do human osteoblasts grow into open-porous titanium?

A titanium foam for spine fusion and other applications was tested by cell culture. Its high porosity and surface roughness should enable bone cells to grow through it, resulting in a better fixation of the vertebral body. The foam was tested by in vitro experiments with human osteoblasts under static culture conditions and in a perfused system. By means of cell number, viability, scanning electron microscopy and histological staining, cell proliferation could be observed. The expression of osteogenic genes like collagen-I, alkaline phosphatase and osteocalcin was proven by reverse transcription polymerase chain reaction (RT-PCR) as well as in the case of alkaline phosphatase with biochemical methods. The conducted experiments showed that human osteoblasts could grow through the interconnected porosity of the metal foam and that they expressed an osteoblast like phenotype. The results suggest that in vivo osteoblasts are likely to form a trabecular bone bridge through this titanium foam. Consequently, with this osteoconductive material, there may be a reduced need for autologous bone in spinal fusion procedures.