Intramedullary Mg2Ag nails augment callus formation during fracture healing in mice

Abstract

Intramedullary stabilization is frequently used to treat long bone fractures. Implants usually remain unless complications arise. Since implant removal can become technically very challenging with the potential to cause further tissue damage, biodegradable materials are emerging as alternative options. Magnesium (Mg)-based biodegradable implants have a controllable degradation rate and good tissue compatibility, which makes them attractive for musculoskeletal research. Here we report for the first time the implantation of intramedullary nails made of an Mg alloy containing 2% silver (Mg2Ag) into intact and fractured femora of mice. Prior in vitro analyses revealed an inhibitory effect of Mg2Ag degradation products on osteoclast differentiation and function with no impair of osteoblast function. In vivo, Mg2Ag implants degraded under non-fracture and fracture conditions within 210 days and 133 days, respectively. During fracture repair, osteoblast function and subsequent bone formation were enhanced, while osteoclast activity and bone resorption were decreased, leading to an augmented callus formation. We observed a widening of the femoral shaft under steady state and regenerating conditions, which was at least in part due to an uncoupled bone remodeling. However, Mg2Ag implants did not cause any systemic adverse effects. These data suggest that Mg2Ag implants might be promising for intramedullary fixation of long bone fractures, a novel concept that has to be further investigated in future studies.

Quantitative characterization of degradation processes in situ by means of a bioreactor coupled flow chamber under physiological conditions using time‐lapse SRµCT

“…, the determined DRs are in better agreement. The comparison with DRs determined in other in vitro studies shows a large discrepancy (0.47 ± 0.04 mm yr −1 after 7 days, 0.34 mm yr −1 after 3 days, ∼0.6 mm yr −1 after 3 days), due to the difference in flow of the culture medium. While it has been shown in Ref.…”

“…In particular, the released concentration of Ag + ions in in vitro experiments was found to be well below toxic concentrations while still antimicrobial efficiency was found . It has been shown in in vivo experiments that the application of Mg‐2Ag implants lead to no difference in the histology of major storage, metabolic and excretion organs …”

“…Mg‐2Ag is a Mg‐alloy that has previously been investigated in in vitro and in vivo degradation studies and has displayed improved mechanical and corrosion properties if subjected to appropriate extrusion and heat pre‐treatment. Furthermore, good biocompatibility and anti‐bacterial properties make it an important binary Mg‐alloy to study .…”

Biodegradable Metallic Wires in Dental and Orthopedic Applications: A Review

“…Although the corrosion rate of Mg2Ag alloy in vivo was three times faster than in vitro, the alloy still showed sufficient rate of biodegradability which maintained proper mechanical stability while supporting fracture healing. Figure 6 illustrates the X-ray images of fractured bone fixed by steel and Mg2Ag wires during 133 days in mice [113]. Finally, they have concluded that Mg2Ag might be a promising material that has a potential application in musculoskeletal medicine.…”

“…Tie et al [112] introduced a novel Mg alloy containing 2% silver (Mg2Ag) and showed that the alloy possessed appropriate mechanical properties and a rather low degradation rate in vitro. In order to assess the in vivo behavior of the alloy, Jahn et al [113] implanted Mg2Ag intramedullary wires into mice with and without a femoral shaft fracture. The wires with the final diameter of 0.8 mm were produced via the cold rolling following the hot extrusion.…”