Improving in vitro and in vivo antibacterial functionality of Mg alloys through micro-alloying with Sr and Ga

Despite of technical advancements in design and development of new biomaterials, device-related infections continue to occur and can be life-threatening. Differing from existing research work pertaining to introducing antibacterial function upon device surface, this study attempts to address such germ-infection issues through controlled release of antibacterial species from bulk gallium (Ga) and strontium (Sr) containing magnesium (Mg) alloys. To validate such a conceptual framework, Mg alloys containing micro-level concentrations of Ga and/or Sr (0.1 wt%) are employed as model materials, along with commercially pure Mg and titanium (Ti) as control groups. Biodegradation progress of such metal specimens is examined through pH and mass loss measurements, and inductively coupled plasma - atomic emission spectrometry (ICP-AES) as a function of immersion time in Trypticase Soy Broth (TSB) solution under physiological conditions. In vitro biocompatibility and antibacterial performance are characterised through MTT proliferation assay with human mesenchymal stem cells (hMSCs) and the spread plate method with three representative bacterial strains, i.e. S. aureus (ATCC 43300), E. coli (ATCC 25922), and S. epidermidis (ATCC 35984). Animal tests are performed through implanting target metal rods into femurs of Sprague Dawley rats, accompanied with injection of S. aureus to build a model of osteomyelitis. Results demonstrate that such lean additions of Ga and/or Sr reduce the degradation kinetics of Mg matrix, and the release of Ga3+ ions plays a crucial role in disabling the viability of all selected bacterial strains. The histological tests confirm that the growth of fibrous tissue has been accelerated in the vicinity of Mg-based implants, in comparison to that of blank and c.p. Ti controls. It is also striking that the smallest number density of S. aureus bacteria on the surface of the retrieved Ga-containing Mg rod implants. Such a proof-of-concept study provides a new and feasible strategy to address the notorious device-infection issues associated with biomedical implants for bone fracture management.