3D printed scaffolds of calcium silicate-doped β-TCP synergize with co-cultured endothelial and stromal cells to promote vascularization and bone formation.

3D printed scaffolds of calcium silicate-doped β-TCP synergize with co-cultured endothelial and stromal cells to promote vascularization and bone formation.
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3D 打印硅酸钙掺杂β-TCP 支架与共培养的内皮细胞和基质细胞协同作用,促进血管化和骨形成

DOI:
10.1038/s41598-017-05196-1
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发表时间:
2017-07-17
期刊:
影响因子:
4.6
通讯作者:
Dai K
Dai K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Deng Y;Jiang C;Li C;Li T;Peng M;Wang J;Dai K

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合成骨支架在修复大骨缺损方面具有潜在的应用前景,然而,植入后血管化效率低下仍然是移植物失败的主要问题。本研究通过3D打印硅酸钙(CS)多孔β-磷酸三钙(β-TCP)支架,并与共培养的人脐带静脉内皮细胞(HUVECs)和人骨髓基质细胞(hBMSCs)预种,构建血管化加快、骨形成更好的组织工程支架。结果表明,5%CS (5%CS/β-TCP)掺杂的体外β-TCP支架具有良好的生物相容性,并能促进血管生成和成骨。结果还表明,5%CS/β-TCP支架不仅能刺激共培养细胞在Matrigel上血管生成,还能刺激共培养细胞在支架上形成微血管样结构,并通过刺激共培养细胞向周围环境分泌PDGF-BB和CXCL12促进BMSCs的迁移。与β-TCP相比,5%CS/β-TCP支架增强了血管形成和骨诱导,并与共培养细胞协同作用,进一步增加了早期血管形成,裸鼠皮下植入后,更早、更好地异位骨形成。因此,我们的研究结果表明,5%CS/β-TCP多孔支架植入共培养细胞,为加速组织工程支架血管化和成骨提供了新的策略,并显示出治疗大型骨缺损的潜力。
Synthetic bone scaffolds have potential application in repairing large bone defects, however, inefficient vascularization after implantation remains the major issue of graft failure. Herein, porous β-tricalcium phosphate (β-TCP) scaffolds with calcium silicate (CS) were 3D printed, and pre-seeded with co-cultured human umbilical cord vein endothelial cells (HUVECs) and human bone marrow stromal cells (hBMSCs) to construct tissue engineering scaffolds with accelerated vascularization and better bone formation. Results showed that in vitro β-TCP scaffolds doped with 5% CS (5%CS/β-TCP) were biocompatible, and stimulated angiogenesis and osteogenesis. The results also showed that 5%CS/β-TCP scaffolds not only stimulated co-cultured cells angiogenesis on Matrigel, but also stimulated co-cultured cells to form microcapillary-like structures on scaffolds, and promoted migration of BMSCs by stimulating co-cultured cells to secrete PDGF-BB and CXCL12 into the surrounding environment. Moreover, 5%CS/β-TCP scaffolds enhanced vascularization and osteoinduction in comparison with β-TCP, and synergized with co-cultured cells to further increase early vessel formation, which was accompanied by earlier and better ectopic bone formation when implanted subcutaneously in nude mice. Thus, our findings suggest that porous 5%CS/β-TCP scaffolds seeded with co-cultured cells provide new strategy for accelerating tissue engineering scaffolds vascularization and osteogenesis, and show potential as treatment for large bone defects.
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