ABSTRACT Although Mg composites show potential in bone repair, the impact of their internal structure on degradation rules and healing mechanisms remains unclear. In this study, we developed four lamellar heterostructural Mg/PLLA composite membranes with considerable mechanical strength using an accumulative roll bonding technology, inspired by the “plywood structure” of native bone and the “muscle exercising” process. Degradation tests proved that precise and programmable delivery of Mg 2+ ions and membrane surface biomineralization could be achieved through structure design. The Mg‐exposed heterostructural membranes facilitated rapid Mg 2 + ion release and spontaneous mineralization on their surface, modulating the immune microenvironment and sequentially activating the neuro–angio–osteogenesis reactions both in vitro and in vivo. In contrast, the Mg‐sealed heterostructural membrane showed limited mineralization even after four weeks, resulting in sluggish bone regeneration and angiogenesis. After thermodynamic calculation, this discrepancy was derived from the PLLA barrier layer significantly slowing Mg corrosion, increasing the Gibbs free energy for hydroxyapatite precipitation on the Mg‐sealed heterostructural membrane surfaces. Furthermore, transcriptomics analysis revealed that the positive regulation of immune response, axon guidance, and cell energy metabolism level activation through the NF‐κB, Rap1, and PI3K‐AKT signaling pathways accounted for its superior bone repair with neuro‐vascularization performance. In short, this study provides new insights into understanding the multiple roles of Mg in bone healing.
Wang et al. (Sat,) studied this question.