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Bio-Design and Manufacturing  2022 Vol.5 No.3 P.540-555

http://doi.org/10.1007/s42242-022-00191-6


3D-printed, bi-layer, biomimetic artificial periosteum for boosting bone regeneration


Author(s):  Yage Sun, Ziwei Gao, Xiaoping Zhang, Ziyang Xu, Yahan Zhang, Binbin He, Rong Yang, Qian Zhang, Qiang Yang & Wenguang Liu

Affiliation(s):  School of Material Science and Engineering, Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin 300350, China; more

Corresponding email(s):   yangqiang1980@126.com, wgliu@tju.edu.cn

Key Words:  3D printing, Bi-layer periosteum scaffold, Immune regulation, Bone regeneration


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Yage Sun, Ziwei Gao, Xiaoping Zhang, Ziyang Xu, Yahan Zhang, Binbin He, Rong Yang, Qian Zhang, Qiang Yang & Wenguang Liu. 3D-printed, bi-layer, biomimetic artificial periosteum for boosting bone regeneration[J]. Journal of Zhejiang University Science D, 2022, 5(3): 540-555.

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journal="Journal of Zhejiang University Science D",
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year="2022",
publisher="Zhejiang University Press & Springer",
doi="10.1007/s42242-022-00191-6"
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Abstract: 
Periosteum, a membrane covering the surface of the bone, plays an essential role in maintaining the function of bone tissue—and especially in providing nourishment and vascularization during the bone regeneration process. Currently, most artificial periostea have relatively weak mechanical strength and a rapid degradation rate, and they lack integrated angiogenesis and osteogenesis functions. In this study, a bi-layer, biomimetic, artificial periosteum composed of a methacrylated gelatin–nano-hydroxyapatite (GelMA-nHA) cambium layer and a poly (N-acryloyl 2-lycine) (PACG) -GelMA-Mg2+ fibrous layer was fabricated via 3D printing. The GelMA-nHA layer is shown to undertake the function of improving osteogenic differentiation of rat bone marrow mesenchymal stem cells with the sustainable release of Ca2+ from nHA nanoparticles. The hydrogen-bonding-strengthened P(ACG-GelMA-L)-Mg2+ hydrogel layer serves to protect the inner defect site and prolong degradation time (60 days) to match new bone regeneration. Furthermore, the released magnesium ion exhibits a prominent effect in regulating the polarization phenotype of macrophage cells into the M2 phenotype and thus promotes the angiogenesis of the human umbilical vein endothelial cells in vitro. This bi-layer artificial periosteum was implanted into a critical-sized cranial bone defect in rats, and the 12-week post-operative outcomes demonstrate optimal new bone regeneration.

天津大学刘文广、天津医院杨强等 | 3D打印双层仿生人工骨膜用于促进骨再生

本研究论文聚焦3D打印双层仿生人工骨膜用于促进骨再生。骨膜是覆盖在骨表面的一层坚韧的结缔组织,对于维持骨组织的功能起到至关重要的作用。目前,大多数人工骨膜具有较弱的机械强度和较快的降解速度,并且难以将成骨功能和血管生成功能整合为一体。鉴于此,在本项研究中,作者通过3D打印技术构建了一种双层仿生人工骨膜,以甲基丙烯酰化明胶 (GelMA) 和羟基磷灰石 (nHA) 作为仿生形成层,以负载镁离子的聚N-丙烯酰基甘氨酸 (PACG) 和GelMA的共聚凝胶作为仿生纤维层。两层中均含有GelMA组分,为挤出打印的实现提供了基础;由于nHA纳米粒子能够释放钙离子,形成层承担了促进骨髓间充质干细胞成骨分化的功能;纤维层的P (ACG-GelMA)-Mg2+水凝胶具有氢键增强的力学强度和长达60天左右的降解时间,起到保护内部缺损部位的功能,并且其中持续释放的镁离子展现出调控巨噬细胞向M2表型极化和促进脐静脉内皮细胞血管生成的功能。这种双层人工骨膜支架植入到大鼠颅骨临界尺寸骨缺损部位后,在术后12周具有最优的新骨生成效果,因而具有明显的促进骨再生作用。

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