Long-term in vivo degradation behaviour and biocompatibility of the magnesium alloy ZEK100 for use as a biodegradable bone implant

Abstract

Magnesium alloys are the focus of research as resorbable materials for osteosynthesis, as they provide sufficient stability and would make surgery to remove implants unnecessary. The new degradable magnesium alloy ZEK100 was developed to improve the stability and corrosion resistance by alloying with zinc, rare earth metals and zirconium. As the implants were degraded to only a limited extent after 6 months implantation in a previous in vivo study the present study was conducted to evaluate the long-term degradation behaviour and biocompatibility in the same animal model over 9 and 12 months. Five rabbits each with intramedullary tibia implants were examined over 9 and 12 months. Three legs were left without an implant to serve as negative controls. Numerous examinations were performed in the follow-up (clinical examinations, serum analysis, and radiographic and in vivo micro-CT investigations) and after death (ex vivo micro-CT, histology, and implant analysis) to assess the in vivo degradation and biocompatibility. It could be shown that favourable in vivo degradation behaviour is not necessarily associated with good biocompatibility. Although ZEK100 provided a very high initial stability and positive biodegradation, it must be excluded from further biomedical testing as it showed pathological effects on the host tissue following complete degradation.

Introduction

In recent years magnesium alloys have become a special focus of biomedical research [1], [2], [3], [4], [5], [6], [7], [8] as they are considered to be suitable for fracture repair of weight-bearing bone [1], [9], [10]. Magnesium alloys are biodegradable and would therefore make surgery for the removal of implants unnecessary [11]. Furthermore, in contrast to conventional metals such as titanium, steel or cobalt–chromium alloys [12], [13], their mechanical properties, which are similar to those of cortical bone [3], [14], prevent stress shielding effects. The advantages of magnesium alloys over commercially available resorbable polymers are the higher mechanical stability [1], [15], [16] and the fact that their corrosion products do not induce as much inflammatory reaction [17].

As the degradation rate of pure magnesium is too high and often results in gas accumulation [18], [19], [20], [21] and, additionally, pure magnesium lacks strength, the influence of alloying with various elements and of different surface treatments have been tested in vitro during recent years [6], [14], [22], [23], [24], [25], [26], [27]. However, as it has been shown that results obtained in vitro do not necessarily predict the in vivo behaviour [28], a substantiated conclusion can only be drawn after in vivo evaluation.

A number of different promising magnesium alloys have been tested in vivo [16], [29], [30], [31], [32], [33], [34], [35], but most of them still lack stability [29], [30], [36] or show a disadvantageous degradation behaviour [29], [36]. Furthermore, most in vivo studies did not observe the complete degradation period, only the beginning of corrosion [16], [32], [33], [37], [38], so biocompatibility during the later stages of degradation have not been well researched. For these reasons the new degradable magnesium alloy ZEK100 was developed to improve the stability and corrosion resistance by alloying with zinc, rare earth metals and zirconium [3], [39] and tested over 6 months in an in vivo study using an orthotopic implantation model [40]. As the implants were degraded to only a limited extent during the examination period and showed favourable degradation characteristics and suitable mechanical properties [40] the present study was conducted to evaluate the long-term degradation behaviour and biocompatibility in the same animal model over 9 and 12 months.