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A synergistic approach to the design, fabrication and evaluation of 3D printed micro and nano featured scaffolds for vascularized bone tissue repair

机译:设计,制造和评估3D打印的微米级和纳米级功能性支架以血管化骨组织修复的协同方法

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摘要

3D bioprinting has begun to show great promise in advancing the development of functional tissue/organ replacements. However, to realize the true potential of 3D bioprinted tissues for clinical use requires the fabrication of an interconnected and effective vascular network. Solving this challenge is critical, as human tissue relies on an adequate network of blood vessels to transport oxygen, nutrients, other chemicals, biological factors and waste, in and out of the tissue. Here, we have successfully designed and printed a series of novel 3D bone scaffolds with both bone formation supporting structures and highly interconnected 3D microvascular mimicking channels, for efficient and enhanced osteogenic bone regeneration as well as vascular cell growth. Using a chemical functionalization process, we have conjugated our samples with nano hydroxyapatite (nHA), for the creation of novel micro and nano featured devices for vascularized bone growth. We evaluated our scaffolds with mechanical testing, hydrodynamic measurements and in vitro human mesenchymal stem cell (hMSC) adhesion (4 h), proliferation (1, 3 and 5 d) and osteogenic differentiation (1, 2 and 3 weeks). These tests confirmed bone-like physical properties and vascular-like flow profiles, as well as demonstrated enhanced hMSC adhesion, proliferation and osteogenic differentiation. Additional in vitro experiments with human umbilical vein endothelial cells also demonstrated improved vascular cell growth, migration and organization on micro-nano featured scaffolds.
机译:3D生物打印已开始在促进功能组织/器官替代物的开发方面显示出巨大的希望。但是,要实现3D生物打印组织在临床上的真正潜力,需要制造相互连接且有效的血管网络。解决这一挑战至关重要,因为人体组织依赖于足够的血管网络来将氧气,营养素,其他化学物质,生物因子和废物运入组织和运出组织。在这里,我们已经成功设计并印刷了一系列新颖的3D骨支架,这些支架都具有骨形成支撑结构和高度互连的3D微血管模拟通道,可有效且增强成骨性骨再生以及血管细胞的生长。使用化学功能化过程,我们将样品与纳米羟基磷灰石(nHA)结合在一起,从而创建了新型的具有微细和纳米特征的用于血管化骨生长的装置。我们通过机械测试,流体力学测量以及体外人间充质干细胞(hMSC)粘附(4 h),增殖(1、3和5 d)和成骨分化(1、2和3周)评估了我们的支架。这些测试证实了类骨的物理特性和类血管的流动特性,并证明了增强的hMSC粘附,增殖和成骨分化。用人脐静脉内皮细胞进行的其他体外实验还表明,在微纳米功能支架上,血管细胞的生长,迁移和组织得以改善。

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