Construction of nanofibrous scaffolds with interconnected perfusable microchannel networks for engineering of vascularized bone tissue.
Construction of nanofibrous scaffolds with interconnected perfusable microchannel networks for engineering of vascularized bone tissue.
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构建具有互连可灌注微通道网络的纳米纤维支架，用于血管化骨组织工程
DOI：
10.1016/j.bioactmat.2021.02.033
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发表时间：
2021-10
影响因子：
18.9
通讯作者：
He C
中科院分区：
文献类型：
--
作者：
Gu J;Zhang Q;Geng M;Wang W;Yang J;Khan AUR;Du H;Sha Z;Zhou X;He C
血管形成和骨再生是骨重建过程中两个密切相关的过程。具有多孔结构的三维支架为血管生长和骨形成提供了合适的微环境。在此，我们提出了一种基于3D打印技术，结合相分离和牺牲模板方法构建具有互连可渗透微通道网络（IPMs）的纳米纤维聚l-丙交酯/聚（ε-己内酯）（PLLA/PCL）支架的简单通用策略。在支架内制作规则的和可定制的微通道模式（间距：0.4 mm， 0.5 mm和0.6 mm；直径：0.8 mm， 1mm和1.2 mm），以研究微通道结构对血管生成和成骨的影响。皮下埋置实验结果表明，与其他支架相比，0.5/0.8- ipms（间距/直径= 0.5/0.8）和0.5/1- ipms（间距/直径= 0.5/1）支架具有更多的血管网络形成。通过Transwell迁移、划伤愈合和绒毛尿囊膜（CAM）检测，VEGF@IPMs-0.5/0.8支架加载血管内皮生长因子（VEGF）后，促进人脐静脉内皮细胞（HUVECs）迁移和新血管形成。此外，微血管造影和大鼠颅骨缺损实验表明，VEGF@IPMs-0.5/0.8支架在血管网络形成和新骨形成方面优于VEGF@IPMs-0.5/1支架。综上所述，我们的研究结果表明，支架内的微通道结构可以通过可调节的焦糖模板策略进行定制，并且相互连接的灌注微通道网络与血管生成因子的结合可以显著增强血管化和骨再生。用于血管化骨组织工程的具有互联可灌注微通道网络的纳米纤维支架示意图。使用3d打印的牺牲模板构建具有互联可渗透微通道网络的支架。支架内的微通道结构可以通过改变模板规格来定制。VEGF在支架微通道中的引入促进了血管网络的形成。支架内微通道结构和血管生成因子显著促进血管化和骨再生。
Vascularization and bone regeneration are two closely related processes during bone reconstruction. A three-dimensional (3D) scaffold with porous architecture provides a suitable microenvironment for vascular growth and bone formation. Here, we present a simple and general strategy to construct a nanofibrous poly(l-lactide)/poly(ε-caprolactone) (PLLA/PCL) scaffold with interconnected perfusable microchannel networks (IPMs) based on 3D printing technology by combining the phase separation and sacrificial template methods. The regular and customizable microchannel patterns within the scaffolds (spacings: 0.4 mm, 0.5 mm, and 0.6 mm; diameters: 0.8 mm, 1 mm, and 1.2 mm) were made to investigate the effect of microchannel structure on angiogenesis and osteogenesis. The results of subcutaneous embedding experiment showed that 0.5/0.8-IPMs (spacing/diameter = 0.5/0.8) and 0.5/1-IPMs (spacing/diameter = 0.5/1) scaffolds exhibited more vascular network formation as compared with other counterparts. After loading with vascular endothelial growth factor (VEGF), VEGF@IPMs-0.5/0.8 scaffold prompted better human umbilical vein endothelial cells (HUVECs) migration and neo-blood vessel formation, as determined by Transwell migration, scratch wound healing, and chorioallantoic membrane (CAM) assays. Furthermore, the microangiography and rat cranial bone defects experiments demonstrated that VEGF@IPMs-0.5/0.8 scaffold exhibited better performance in vascular network formation and new bone formation compared to VEGF@IPMs-0.5/1 scaffold. In summary, our results suggested that the microchannel structure within the scaffolds could be tailored by an adjustable caramel-based template strategy, and the combination of interconnected perfusion microchannel networks and angiogenic factors could significantly enhance vascularization and bone regeneration. Schematic diagram of nanofibrous scaffolds with interconnected perfusable microchannel networks for engineering of vascularized bone tissue. 3D-printed sacrificial templates are used to construct the scaffold with interconnected perfusable microchannel networks. The microchannel structure within scaffolds can be tailored by changing the template specifications. The introduction of VEGF in the microchannel of scaffold promotes the vascular network formation. Microchannel structure and angiogenic factor within scaffold significantly enhance vascularization and bone regeneration.
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影响因子：
29.4
作者：
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通讯作者：
Kong, Hyunjoon
影响因子：
15.9
作者：
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DOI：
10.1016/j.msec.2019.110622
发表时间：
2020-05-01
影响因子：
7.9
作者：
Liu, Yang;Yang, Shengbing;Liu, Changsheng
通讯作者：
Liu, Changsheng
影响因子：
25
作者：
Blinder, Pablo;Tsai, Philbert S.;Kaufhold, John P.;Knutsen, Per M.;Suhl, Harry;Kleinfeld, David
通讯作者：
Kleinfeld, David