Lithium-containing bioactive glasses enhanced 3D-printed PLGA scaffolds for bone regeneration in diabetes
Lithium-containing bioactive glasses enhanced 3D-printed PLGA scaffolds for bone regeneration in diabetes
复制标题
含锂生物活性玻璃增强 3D 打印 PLGA 支架，用于糖尿病骨再生
DOI：
10.1016/j.compositesb.2021.109550
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发表时间：
2021-12-06
影响因子：
13.1
通讯作者：
Liu, Jiaqiang
中科院分区：
文献类型：
--
作者：
Chen, Yu;Chen, Long;Liu, Jiaqiang
糖尿病患者骨缺损的修复是临床治疗中的一个挑战，主要是因为干细胞功能障碍导致成骨抑制。我们的研究发现，高糖诱导GSK-3 β活化，GSK-3 β在这一过程中发挥了重要作用。抑制GSK-3 β诱导了可接受的锂离子成骨作用。然而，含锂生物材料是否能在DM病理状态下发挥良好的骨修复作用尚不清楚。为此，我们合成了一种含锂介孔生物活性玻璃（Li-MBG），并探讨了其在体外高糖微环境下对骨髓间充质干细胞增殖、迁移和成骨分化的调控作用及其机制。同时，采用3D打印技术制备Li-MBG/PLGA复合支架，研究其在体内修复DM小鼠颅骨严重缺损的效果。我们发现Li-MBG通过上调Itga3和激活β -catenin/Tcf7/Ccn4信号通路，逆转了高糖诱导的BMSCs增殖、迁移和成骨分化的抑制。Li-MBG/PLGA复合支架可通过募集干细胞有效修复DM小鼠颅骨缺损，具有良好的成骨效果。本研究结果可为糖尿病患者骨缺损修复提供临床参考。
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-3 beta, which played an important role in this process. Inhibited GSK-3 beta 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 beta-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.