Lithium-containing bioactive glasses enhanced 3D-printed PLGA scaffolds for bone regeneration in diabetes

The repair of bone defects in patients with diabetes mellitus (DM) is a challenge in clinical treatment mainly because of inhibited osteogenesis caused by stem cell dysfunction. Our research found that high glucose induced the activation of GSK-3β, which played an important role in this process. Inhibited GSK-3β induced an acceptable osteogenic effect of lithium ions. However, whether lithium-containing biomaterials can exert a good bone-repair effect under the pathological state of DM is still unclear. Therefore, we synthesized a type of lithium-containing mesoporous bioactive glasses (Li-MBG), and explored their in vitro roles in regulating the proliferation, migration and osteogenic differentiation of BMSCs under the high-glucose microenvironment, and the underlying mechanism. Meanwhile, Li-MBG/PLGA composite scaffolds were prepared by 3D printing, followed by investigating their in vivo effects on repairing critical skull defects of DM mice. We found that Li-MBG reversed high glucose-induced suppression in the proliferation, migration and osteogenic differentiation of BMSCs by upregulating Itga3 and activating the β-catenin/Tcf7/Ccn4 signaling pathway. Li-MBG/PLGA composite scaffolds could effectively repair skull defects of DM mice by recruiting stem cells, presenting an excellent osteogenesis effect. Our findings provide references for clinical bone defect repair in DM patients.