Opportunities and challenges for the biodegradable magnesium alloys as next-generation biomaterials

Abstract

In recent years, biodegradable magnesium alloys emerge as a new class of biomaterials for tissue engineering and medical devices. Deploying biodegradable magnesium-based materials not only avoids a second surgical intervention for implant removal but also circumvents the long-term foreign body effect of permanent implants. However, these materials are often subjected to an uncontrolled and fast degradation, acute toxic responses and rapid structural failure presumably due to a localized, too rapid corrosion process. The patented Mg-Nd-Zn-based alloys (JiaoDa BioMg [JDBM]) have been developed in Shanghai Jiao Tong University in recent years. The alloy series exhibit lower biodegradation rate and homogeneous nanophasic degradation patterns as compared with other biodegradable Mg alloys. The in vitro cytotoxicity tests using various types of cells indicate excellent biocompatibility of JDBM. Finally, bone implants using JDBM-1 alloy and cardiovascular stents using JDBM-2 alloy have been successfully fabricated and in vivo long-term assessment via implantation in animal model have been performed. The results confirmed the reduced degradation rate in vivo, excellent tissue compatibility and long-term structural and mechanical durability. Thus, this novel Mg-alloy series with highly uniform nanophasic biodegradation represent a major breakthrough in the field and a promising candidate for manufacturing the next generation biodegradable implants.

Keywords: biodegradable material; cardiovascular stents; magnesium alloys; orthopaedic implants; uniform corrosion.

Figure 1.

Mechanical property matching between new bones and implants

Figure 2.

Distribution of dynamic absorption and excretion equilibrium of Mg in human body [8]

Figure 3.

Surface morphology and the schematic diagram of the corresponding degradation mechanism of JDBM (a and b), WE43 (c and d) and AZ31 (e and f) alloys. The surface of the new JDBM alloy upon exposure to artificial plasma displays a highly uniformarray of nanopits with typical size <500 nm. In contrast, both WE43 and AZ31 alloys show macroscopic pitting or delamination that dominates the degradation process and results in a fast degradation rate and ultimately structural failure [22]

Figure 4.

Mechanical properties of (a) JDBM-1 with high strength and moderate ductility; and (b) JDBM-2 with high ductility and moderate strength

Figure 5.

Various bone implants fabricated using JDBM-1 alloy, including bone plates, screws and porous bone tissue scaffold

Figure 6.

Cardiovascular stents fabricated using JDBM-2 alloys

Figure 7.

In vitro corrosion rate measured with immersion test showing a much lower rate of JDBM compared with that of WE43 [23]

Figure 8.

(a) Macroscopic picture of a brushite-coated JDBM sample, (b) scanning electron microscope (SEM) image of the brushite coating on JDBM substrate and (c) cross-section view of the brushite coating [24]

Figure 9.

In vivo degradation morphology of bone plates fabricated with (a) JDBM, (b) JDBM covered with brushite coating, (c) AZ31 and (d) WE43, at 18 weeks post-implantation into rabbits

Figure 10.

Statistical results of cytotoxicity assays using Human Umbilical Vein Endothelial Cells (HUVEC) incubated with JDBM, WE43, AZ31 extracts, respectively [25]

Figure 11.

HUVEC morphology after incubated for 24 h with the extracts of (a) negative control, (b) JDBM-2 and (c) WE43 [25]

Figure 12.

The as-implanted (a and c) and 16-week follow-up (b and d) angiographic and the corresponding longitudinal reconstruction Intravascular Ultrasound (IVUS) images of the abdominal aorta after JDBM stent implantation. Note the increased plaque volume and vessel size (arrow heads) at 16 weeks with the nearly complete absence of neointimal hyperplasia [26]