In vivo assessment of the host reactions to the biodegradation of the two novel magnesium alloys ZEK100 and AX30 in an animal model

Abstract

Background: Most studies on biodegradable magnesium implants published recently use magnesium-calcium-alloys or magnesium-aluminum-rare earth-alloys.However, since rare earths are a mixture of elements and their toxicity is unclear, a reduced content of rare earths is favorable. The present study assesses the in vivo biocompatibility of two new magnesium alloys which have a reduced content (ZEK100) or contain no rare earths at all (AX30).

Methods: 24 rabbits were randomized into 4 groups (AX30 or ZEK100, 3 or 6 months, respectively) and cylindrical pins were inserted in their tibiae. To assess the biodegradation μCT scans and histological examinations were performed.

Results: The μCT scans showed that until month three ZEK100 degrades faster than AX30, but this difference is leveled out after 6 months. Histology revealed that both materials induce adverse host reactions and high numbers of osteoclasts in the recipient bone. The mineral apposition rates of both materials groups were high.

Conclusions: Both alloys display favorable degradation characteristics, but they induce adverse host reactions, namely an osteoclast-driven resorption of bone and a subsequent periosteal formation of new bone. Therefore, the biocompatibility of ZEK100 and AX30 is questionable and further studies, which should focus on the interactions on cellular level, are needed.

Figure 1

Details of osteoclasts in TRAP staining. [a] Osteoclast on endosteal surface [b] Cortical cavity with osteoclasts. Black arrows: TRAP positive bone of Howship-lacunes, black star: TRAP positive staining of cement lines, black bar: scale bar 50 μm.

Figure 2

Fluorochrome labeling for histomorphometry. [a] Labels of the four fluorochromes used (1 Calcein green, 2 Xylenol orange, 3 Calcein blue, 4 Tetracycline) [b] Positions for the measurement of the distance between the labels (same slices)

Figure 3

Details of Toluidine blue stained slices. [a] slice of an animal of the 6 months control group. [b] slice of the ZEK100 6 months group. [c] slice of the ZEK100 6 months group (yellow star: artefact due to preparation, white arrow: periosteal remodelling, red arrow: endosteal remodelling, black arrow: periosteal formation of new bone, green arrow: periimplant fibrosis)

Figure 4

Details of cortical bone and adjacent bone marrow. [a] 3 months control group [b] ZEK100 3 months group.

Figure 5

Details of a Toluidine blue stained slice of the ZEK100 3 months group. [a] Bone marrow between endost and implant (red arrows: foreign body giant cells) [b] Bone marrow close to endost with trabecular formation of new bone (green arrows: osteoneogenesis, layer of osteoblasts on light unmineralised osteoid and dark blue mineralised bone, red arrow: endosteal remodelling, yellow arrow: macrophage)

Figure 6

Average periosteal mineral apposition rate (MAR).