PLA/Hydroxyapatite scaffolds exhibit in vitro immunological inertness and promote robust osteogenic differentiation of human mesenchymal stem cells without osteogenic stimuli.

PLA/Hydroxyapatite scaffolds exhibit in vitro immunological inertness and promote robust osteogenic differentiation of human mesenchymal stem cells without osteogenic stimuli.
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DOI:
10.1038/s41598-022-05207-w
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发表时间:
2022-02-11
期刊:
影响因子:
4.6
通讯作者:
Sechi A
Sechi A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Bernardo MP;da Silva BCR;Hamouda AEI;de Toledo MAS;Schalla C;Rütten S;Goetzke R;Mattoso LHC;Zenke M;Sechi A

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骨缺损是重建外科面临的最大挑战之一。熔融沉积建模(FDM)允许以患者特定和高精度的方式打印根据骨损伤的形态和大小量身定做的3D支架。然而,fdm仍然缺乏能够有效支持成骨的材料。本研究以高陶瓷含量(w/w)为20%以上的聚乳酸/羟基磷灰石(PLA/HA)复合材料为材料,采用有限差示扫描量热法制备了三维打印多孔支架材料。聚乳酸/羟基磷灰石支架的力学性能与松质骨的力学性能基本一致。体外降解实验表明,HA可以中和聚乳酸降解引起的酸化效应,同时释放钙和磷离子。重要的是,3D打印的PLA/HA没有诱导树突状细胞中激活标志物的上调,也没有炎性细胞因子的表达,因此在体外没有表现出免疫刺激特性。对人骨髓间充质干细胞(MSC)的评价表明,纯的聚乳酸支架具有良好的成骨作用,而聚乳酸/羟基磷灰石支架即使在没有任何典型的成骨刺激的情况下也能有效地诱导MSC向成骨细胞分化。我们的研究结果表明,负载高浓度HA的3D打印聚乳酸支架最适合于未来的骨组织工程应用。
Bone defects stand out as one of the greatest challenges of reconstructive surgery. Fused deposition modelling (FDM) allows for the printing of 3D scaffolds tailored to the morphology and size of bone damage in a patient-specific and high-precision manner. However, FDM still suffers from the lack of materials capable of efficiently supporting osteogenesis. In this study, we developed 3D-printed porous scaffolds composed of polylactic acid/hydroxyapatite (PLA/HA) composites with high ceramic contents (above 20%, w/w) by FDM. The mechanical properties of the PLA/HA scaffolds were compatible with those of trabecular bone. In vitro degradation tests revealed that HA can neutralize the acidification effect caused by PLA degradation, while simultaneously releasing calcium and phosphate ions. Importantly, 3D-printed PLA/HA did not induce the upregulation of activation markers nor the expression of inflammatory cytokines in dendritic cells thus exhibiting no immune-stimulatory properties in vitro. Evaluations using human mesenchymal stem cells (MSC) showed that pure PLA scaffolds exerted an osteoconductive effect, whereas PLA/HA scaffolds efficiently induced osteogenic differentiation of MSC even in the absence of any classical osteogenic stimuli. Our findings indicate that 3D-printed PLA scaffolds loaded with high concentrations of HA are most suitable for future applications in bone tissue engineering.
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