The combined effect of zinc and calcium on the biodegradation of ultrahigh-purity magnesium implants.

Magnesium (Mg)-based implants are promising candidates for orthopedic interventions, because of their biocompatibility, good mechanical features, and ability to degrade completely in the body, eliminating the need for an additional removal surgery. In the present study, we synthesized and investigated two Mg-based materials, ultrahigh-purity ZX00 (Mg-Zn-Ca; <0.5 wt% Zn and <0.5 wt% Ca, in wt%; Fe-content <1 ppm) and ultrahigh-purity Mg (XHP-Mg, >99.999 wt% Mg; Fe-content <1 ppm), in vitro and in vivo in juvenile healthy rats to clarify the effect of the alloying elements Zn and Ca on mechanical properties, microstructure, cytocompatibility and degradation rate. Potential differences in bone formation and bone in-growth were also assessed and compared with state-of-the-art non-degradable titanium (Ti)-implanted, sham-operated, and control (non-intervention) groups, using micro-computed tomography, histology and scanning electron microscopy. At 6 and 24 weeks after implantation, serum alkaline phosphatase (ALP), calcium (Ca), and Mg level were measured and bone marrow stromal cells (BMSCs) were isolated for real-time PCR analysis. Results show that ZX00 implants have smaller grain size and superior mechanical properties than XHP-Mg, and that both reveal good biocompatibility in cytocompatibilty tests. ZX00 homogenously degraded with an increased gas accumulation 12 and 24 weeks after implantation, whereas XHP-Mg exhibited higher gas accumulation already at 2 weeks. Serum ALP, Ca, and Mg levels were comparable among all groups and both Mg-based implants led to similar relative expression levels of Alp, Runx2, and Bmp-2 genes at weeks 6 and 24. Histologically, Mg-based implants are superior for new bone tissue formation and bone in-growth compared to Ti implants. Furthermore, by tracking the sequence of multicolor fluorochrome labels, we observed higher mineral apposition rate at week 2 in both Mg-based implants compared to the control groups. Our findings suggest that (i) ZX00 and XHP-Mg support bone formation and remodeling, (ii) both Mg-based implants are superior to Ti implants in terms of new bone tissue formation and osseointegration, and (iii) ZX00 is more favorable due to its lower degradation rate and moderate gas accumulation.

Implant degradation of low-alloyed Mg-Zn-Ca in osteoporotic, old and juvenile rats.

Implant removal is unnecessary for biodegradable magnesium (Mg)-based implants and, therefore, the related risk for implant-induced fractures is limited. Aging, on the other hand, is associated with low bone-turnover and decreased bone mass and density, and thus increased fracture risk. Osteoporosis is accompanied by Mg deficiency, therefore, we hypothesized that Mg-based implants may support bone formation by Mg2+ ion release in an ovariectomy-induced osteoporotic rat model. Hence, we investigated osseointegration and implant degradation of a low-alloyed, degrading Mg-Zn-Ca implant (ZX00) in ovariectomy-induced osteoporotic (Osteo), old healthy (OH), and juvenile healthy (JH) groups of female Sprague Dawley rats via in vivo micro-computed tomography (µCT). For the Osteo rats, we demonstrate diminished trabecular bone already after 8 weeks upon ovariectomy and significantly enhanced implant volume loss, with correspondingly pronounced gas formation, compared to the OH and JH groups. Sclerotic rim development was observed in about half of the osteoporotic rats, suggesting a prevention from foreign-body and osteonecrosis development. Synchrotron radiation-based µCT confirmed lower bone volume fractions in the Osteo group compared to the OH and JH groups. Qualitative histological analysis additionally visualized the enhanced implant degradation in the Osteo group. To date, ZX00 provides an interesting implant material for young and older healthy patients, but it may not be of advantage in pharmacologically untreated osteoporotic conditions. STATEMENT OF SIGNIFICANCE: Magnesium-based implants are promising candidates for treatment of osteoporotic fractures because of their biodegradable, biomechanical, anti-bacterial and bone regenerative properties. Here we investigate magnesium‒zinc‒calcium implant materials in a rat model with ovariectomy-induced osteoporosis (Osteo group) and compare the related osseointegration and implant degradation with the results obtained for old healthy (OH) and juvenile healthy (JH) rats. The work applied an appropriate disease model for osteoporosis and focused in particular on long-term implant degradation for different bone conditions. Enhanced implant degradation and sclerotic rim formation was observed in osteoporotic rats, which illustrates that the setting of different bone models generates significantly modified clinical outcome. It further illustrated that these differences must be taken into account in future biodegradable implant development.

A lean magnesium-zinc-calcium alloy ZX00 used for bone fracture stabilization in a large growing-animal model.

Over the last decade, demand has increased for developing new, alternative materials in pediatric trauma care to overcome the disadvantages associated with conventional implant materials. Magnesium (Mg)-based alloys seem to adequately fulfill the vision of a homogeneously resorbable, biocompatible, load-bearing and functionally supportive implant. The aim of the present study is to introduce the high-strength, lean alloy Mg‒0.45Zn‒0.45Ca, in wt% (ZX00), and for the first time investigate the clinical applicability of screw osteosynthesis using this alloy that contains no rare-earth elements. The alloy was applied in a growing sheep model with osteotomized bone (simulating a fracture) and compared to a non-osteotomy control group regarding degradation behavior and fracture healing. The alloy exhibits an ultimate tensile strength of 285.7 ± 3.1 MPa, an elongation at fracture of 18.2 ± 2.1%, and a reduced in vitro degradation rate compared to alloys containing higher amounts of Zn. In vivo, no significant difference between the osteotomized bone and the control group was found regarding the change in screw volume over implantation time. Therefore, it can be concluded that the fracture healing process, including its effects on the surrounding area, has no significant influence on degradation behavior. There was also no negative influence from hydrogen-gas formation on fracture healing. Despite the proximal and distal screws showing chronologically different gas release, the osteotomy showed complete consolidation. STATEMENT OF SIGNIFICANCE: Conventional implants involve several disadvantages in pediatric trauma care. Magnesium-based alloys seem to overcome these issues as discussed in the recent literature. This study evaluates the clinical applicability of high-strength lean Mg‒0.45Zn‒0.45Ca (ZX00) screws in a growing-sheep model. Two groups, one including a simulated fracture and one group without fracture, underwent implantation of the alloy and were compared to each other. No significant difference regarding screw volume was observed between the groups. There was no negative influence of hydrogen-gas formation on fracture healing and a complete fracture consolidation was found after 12 weeks for all animals investigated.

Laser additive manufacturing of biodegradable magnesium alloy WE43: A detailed microstructure analysis.

WE43, a magnesium alloy containing yttrium and neodymium as main alloying elements, has become a well-established bioresorbable implant material. Implants made of WE43 are often fabricated by powder extrusion and subsequent machining, but for more complex geometries laser powder bed fusion (LPBF) appears to be a promising alternative. However, the extremely high cooling rates and subsequent heat treatment after solidification of the melt pool involved in this process induce a drastic change in microstructure, which governs mechanical properties and degradation behaviour in a way that is still unclear. In this study we investigated the changes in the microstructure of WE43 induced by LPBF in comparison to that of cast WE43. We did this mainly by electron microscopy imaging, and chemical mapping based on energy-dispersive X-ray spectroscopy in conjunction with electron diffraction for the identification of the various phases. We identified different types of microstructure: an equiaxed grain zone in the center of the laser-induced melt pool, and a lamellar zone and a partially melted zone at its border. The lamellar zone presents dendritic lamellae lying on the Mg basal plane and separated by aligned Nd-rich nanometric intermetallic phases. They appear as globular particles made of Mg3Nd and as platelets made of Mg41Nd5 occurring on Mg prismatic planes. Yttrium is found in solid solution and in oxide particles stemming from the powder particles' shell. Due to the heat influence on the lamellar zone during subsequent laser passes, a strong texture developed in the bulk material after substantial grain growth. STATEMENT OF SIGNIFICANCE: Additively manufactured magnesium alloys have the potential of providing a major breakthrough in bone-reconstruction surgery by serving as biodegradable porous scaffold material. This study is the first to report in detail on the microstructure development of the established magnesium alloy WE43 fabricated by the additive manufacturing process of Laser Powder Bed Fusion (LPBF). It presents unique microstructural features which originate from the laser-melting process. An in situ transmission electron microscopy heating experiment further demonstrates the development of two distinct intermetallic phases in additively manufactured WE43 alloys. While one forms already during solidification, the other precipitates due to the ongoing heat treatment during LPBF processing.

Advanced interlocking systems to improve heavy-load-bearing characteristics of flexible intramedullary nailing.

Flexible intramedullary nailing (FIN) is a minimally invasive and widespread standard method for osteosynthesis of pediatric long bone fractures. In the case of unstable fractures of the lower extremity, interlocking systems need to be used to prevent axial shortening and subsequent perforation of the nail at its insertion site. In the present study, four different screw-fixed interlocking systems for FINs (Hofer TwinPlug with two 3-mm titanium interlocking screws, Hofer FixPlug with 3-mm titanium interlocking screw, Hofer Plug with 3.5-mm titanium interlocking screw, and Hofer Plug with 3-mm titanium interlocking screw) in comparison with the commonly used Ender stainless steel nails (locked with 3.5-mm screw) were experimentally investigated in cadaveric lamb tibiae, regarding their load characteristics and failure modes in the case of heavy loading. The specimens were subjected to sequential axial cyclic loading of 5000cycles with stepwise increase of the load amplitude until failure. Migration of locking screws and internal damage of bone tissue was quantified by micro-computed tomography (CT) imaging. Ender nails failed on average at a peak load of 800 N, TwinPlugs at 1367 N, FixPlugs at 1222 N, Plugs 3.5mm at 1225 N and Plugs 3.0mm at 971 N. TwinPlugs, FixPlugs, and Plugs 3.5mm failed in a slow manner over several hundred loading cycles, whereas Ender nails and Plugs 3.0mm exhibited abrupt failure without any prior indication. Our results confirm that axial stability of FIN can be further improved by screw-fixed plugs by simultaneously avoiding shortcomings of an eye-locked system, which the Ender nails are. Considering biomechanical results, plug interlocking systems with 3.5-mm screws should be favored over conventional Ender nails and plugs with 3-mm screws.

Unlocked and locked elastic stable intramedullary nailing in an ovine tibia fracture model: a biomechanical study.

In the present study, four different systems of elastic stable intramedullary nails (unlocked, Ender stainless steel nails locked with 3-mm screws, titanium nails locked with end caps, titanium nails locked with plugs and 3-mm screws) were implanted in cadaveric ovine tibiae. Fractures were simulated by a transverse diaphyseal osteotomy. The specimens were subjected to simultaneous axial and torsional fatigue loading of 5000 and 1000 cycles, respectively. The unlocked systems failed at an axial load of 200 N peak amplitude. End caps systems withstood axial loads up to 800 N for 1000 cycles, and ender nails and plugs lasted up to 1000 N for 1000 cycles. All systems showed a decrease of axial stiffness with higher loads and endured cycles. Ender nails and nails locked with plugs failed by penetration of the distal epiphysis rather than by loosening of the interlocking system. Overall, the titanium nails locked with plugs and 3-mm screws exhibited superior test results.