Abstract

Today, substantial attention is given to biomaterial strategies for bone regeneration, and among them, there is a growing interest in using immunomodulatory biomaterials. The ability of a biomaterial to induce neo vascularization and macrophage polarization is a major factor in defining its success. Magnesium (Mg)-based degradable alloys have attracted significant attention for bone regeneration owing to their biodegradability and potential for avoiding secondary removal surgeries. However, there is insufficient evidence in the literature regarding the early inflammatory responses to these alloys in vivo. In this study, we investigated the early body responses to Mg-0.45wt%Zn-0.45wt%Ca pin-shaped alloy (known as ZX00 alloy) in rat femora 2, 5, and 10 days after implantation. We used 3D micro computed tomography (µCT), histological, immunohistochemical, histomorphometrical, and small angle X-ray scattering (SAXS) analyses to study new bone formation, early macrophage polarization, neo vascularization, and bone quality at the implant bone interface. The expression of macrophage type 2 biological markers increased significantly after 10 days of Mg alloy implantation, indicating its potential in stimulating macrophage polarization. Our biomineralization results using µCT as well as histological stained sections did not indicate any statistically significant differences between different time points for both groups. The activity of alkaline phosphatase (ALP) and Runt-related transcription factor 2 (Runx 2) biological markers decreased significantly for Mg group, indicating less osteoblast activity. Generally, our results supported the potential of ZX00 alloy to enhance the expression of macrophage polarization in vivo; however, we could not observe any statistically significant changes regarding biomineralization.

Highlights

  • Bone fracture is a major cause of severe physical disability and global socio-economic burden.[1,2,3] Over the past few decades, biomaterials and interface tissue engineering fields have made considerable progress in suggesting promising strategies to stimulate tissue regeneration after bone tissue damage and/or loss caused by trauma, pathology, and resorption.[4,5,6] Traditionally, titanium alloys are considered the gold standard for stabilizing bone fractures.[7]

  • The purified Mg was alloyed with zinc and calcium to synthesize the Mg-0.45wt%Zn-0.45wt%Ca pin-shaped alloy with a diameter of 1.6 mm and length of 8 mm

  • We evaluated the early host responses to Mg 0.45wt%Zn-0.45wt%Ca pin-shaped alloy in juvenile rat animals 2, 5, and 10 days after implantation

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Summary

Introduction

Bone fracture is a major cause of severe physical disability and global socio-economic burden.[1,2,3] Over the past few decades, biomaterials and interface tissue engineering fields have made considerable progress in suggesting promising strategies to stimulate tissue regeneration after bone tissue damage and/or loss caused by trauma, pathology, and resorption.[4,5,6] Traditionally, titanium alloys (known as bio-inert metallic implants) are considered the gold standard for stabilizing bone fractures.[7]. Biocompatibility, corrosion resistance, and closer modulus to bone.[8,9,10,11,12] due to some limitations (such as stress shielding and secondary operations for implant removal), bio-inert non-degradable implants could not be an optimal choice for bone regeneration.[13,14,15] A perfect internal fixation device should degrade and reduce its stiffness over time as the fracture heals and does not need secondary operations for implant removal.[15]

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