Magnesium–aluminum (Mg–Al) alloys are promising candidates for biodegradable implants, offering a favorable balance of mechanical strength and corrosion resistance. However, the release and systemic fate of aluminum (Al) during alloy degradation remain poorly understood, especially in relation to their microstructure. In this study, we investigate the role of β–Mg17Al12 precipitates in governing early-stage corrosion and Al release from Mg–9Al alloys under both in-vitro and in-vivo conditions. In-vitro immersion testing revealed that peak-aged (PA) samples, containing a high density of β–Mg17Al12 precipitates, exhibited accelerated pitting corrosion and higher total Al release compared to solution-treated (ST) samples. In contrast, in-vivo subcutaneous implantation demonstrated the opposite trend regarding Al release with ST implants yielding higher systemic Al ion levels, whereas PA implants retained more particulate β–Mg17Al12 and corrosion products at the implantation site. This behavior is attributed to differences in Al speciation and mobilization, with Al from ST alloys releasing primarily in solute form and Al from PA alloys predominantly present as highly elongated precipitate fragments that remained localized and resisted systemic transport. These findings underscore that microstructure influences not only early-stage corrosion kinetics but also the early-stage bioavailability and physiological distribution of Al degradation products. This work provides a framework for designing Mg-based alloys that balance mechanical performance with favorable physiological clearance, advancing the development of safe and effective biodegradable implants.

Statement of Significance

Biodegradable Mg–Al alloys, exemplified by the recent FDA-authorized Biotronik Freesolve stent, hold great promise for temporary medical implants. Yet, the role of microstructure in governing aluminum release and systemic exposure has remained poorly understood. Here, we demonstrate for the first time that Al speciation and mobilization dynamics in-vivo are critically dictated by microstructural design. Peak-aged alloys containing β–Mg17Al12 precipitates favor localized, particulate Al release with minimal systemic transport, whereas solution-treated alloys release Al predominantly as ionic and oxide species, yielding higher systemic levels despite lower total Al loss in-vitro. These findings reveal a pivotal link between microstructure and biological fate, providing a mechanistic foundation for engineering next-generation Mg-based biomaterials.