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具有增强成骨作用的可生物降解哌嗪基聚氨酯脲支架的三维打印用于骨再生。

Three-Dimensional Printing of Biodegradable Piperazine-Based Polyurethane-Urea Scaffolds with Enhanced Osteogenesis for Bone Regeneration.

机构信息

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering , Chongqing University , Chongqing 400030 , China.

Key Laboratory of Shenzhen Renal Diseases, Department of Nephrology, First Affiliated Hospital of Southern University of Science and Technology, Second Clinical Medical College of Jinan University , Shenzhen People's Hospital , Shenzhen , Guangdong 518020 , China.

出版信息

ACS Appl Mater Interfaces. 2019 Mar 6;11(9):9415-9424. doi: 10.1021/acsami.8b20323. Epub 2019 Feb 13.

DOI:10.1021/acsami.8b20323
PMID:30698946
Abstract

Synthetic biodegradable polymeric scaffolds with uniformly interconnected pore structure, appropriate mechanical properties, excellent biocompatibility, and even enhanced osteogenesis ability are urgently required for in situ bone regeneration. In this study, for the first time, a series of biodegradable piperazine (PP)-based polyurethane-urea (P-PUU) scaffolds with a gradient of PP contents were developed by air-driven extrusion 3D printing technology. The P-PUU ink of 60 wt % concentration was demonstrated to have appropriate viscosity for scaffold fabrication. The 3D-printed P-PUU scaffolds exhibited an interconnected porous structure of about 450 μm in macropore size and about 75% in porosity. By regulating the contents of PP in P-PUU scaffolds, their mechanical properties could be moderated, and P-PUU1.4 scaffolds with the highest PP contents exhibited the highest compressive modulus (155.9 ± 5.7 MPa) and strength (14.8 ± 1.1 MPa). Moreover, both in vitro and in vivo biological results suggested that the 3D-printed P-PUU scaffolds possessed excellent biocompatibility and osteoconductivity to facilitate new bone formation. The small molecular PP itself was confirmed for the first time to regulate osteogenesis of osteoblasts in a dose-dependent manner and the optimum concentration for osteoconductivity was about ∼0.5 mM, which suggests that PP molecules, together with the mechanical behavior, nitrogen-contents, and hydrophilicity of P-PUUs, play an important role in enhancing the osteoconductive ability of P-PUU scaffolds. Therefore, the 3D-printed P-PUU scaffolds, with suitable interconnected pore structure, appropriate mechanical properties, and intrinsically osteoconductive ability, should provide a promising alternative for bone regeneration.

摘要

具有均匀互联孔结构、适当机械性能、优异生物相容性且甚至增强成骨能力的合成可生物降解聚合物支架,对于原位骨再生是迫切需要的。在本研究中,首次通过气流驱动挤出 3D 打印技术开发了一系列具有梯度哌嗪(PP)含量的可生物降解哌嗪(PP)基聚氨酯脲(P-PUU)支架。浓度为 60wt%的 P-PUU 墨水被证明具有适当的支架制造粘度。3D 打印的 P-PUU 支架表现出约 450μm 的大孔尺寸和约 75%的多孔率的互联多孔结构。通过调节 P-PUU 支架中 PP 的含量,可以调节其机械性能,并且具有最高 PP 含量的 P-PUU1.4 支架表现出最高的压缩模量(155.9±5.7MPa)和强度(14.8±1.1MPa)。此外,体外和体内生物学结果表明,3D 打印的 P-PUU 支架具有优异的生物相容性和骨诱导性,有利于新骨形成。首次证实小分子 PP 本身以剂量依赖性方式调节成骨细胞的成骨作用,并且最佳的骨诱导浓度约为~0.5mM,这表明 PP 分子与 P-PUUs 的机械行为、氮含量和亲水性一起在增强 P-PUU 支架的骨诱导能力方面起着重要作用。因此,具有合适互联孔结构、适当机械性能和固有骨诱导能力的 3D 打印 P-PUU 支架应为骨再生提供有前途的替代方案。

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