Engineering Pre-vascularized Scaffolds for Bone Regeneration
Engineering Pre-vascularized Scaffolds for Bone Regeneration
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DOI：
10.1007/978-3-319-22345-2_5
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发表时间：
2015-01-01
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影响因子：
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通讯作者：
Bertassoni, Luiz E.
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文献类型：
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作者：
Barabaschi, Giada D. G.;Manoharan, Vijayan;Bertassoni, Luiz E.
临床相关尺寸的功能性组织构建体的存活取决于有组织且均匀分布的血管和毛细血管网络的形成。缺乏这样的脉管系统导致氧、营养物的时空梯度和工程化组织构建体内废物的积累，导致支架核心处的负面生物事件。明确界定的脉管系统的不可用也导致支架在植入时与宿主脉管系统的无效整合。因此，可以说，在工程化临床相关的骨替代物中最大的挑战之一是血管化骨支架的开发。已经提出了从肽和生长因子功能化生物材料到多孔支架的各种方法来解决这个问题，并取得了合理的成功。解决这一挑战的一种新兴替代方案是通过利用生物制造技术（例如软光刻和光刻或3D生物打印）和基于细胞的方法来制造预血管化支架，其中在植入之前在载有细胞的支架中设计功能性毛细血管。这些策略寻求在体外工程化预血管化的组织，允许在植入时改善与宿主脉管系统的吻合，同时还改善体外细胞活力和组织发育。这本书的章节提供了一个概述最近的方法工程预血管化支架骨再生。我们首先回顾了功能性毛细血管在骨结构中的发展，并讨论了生长因子的控制输送，共培养系统和芯片上的研究，以工程师血管化的细胞负载的生物材料。最后，我们回顾了最近的研究，利用微加工技术和3D打印工程预血管化支架骨组织工程。
Survival of functional tissue constructs of clinically relevant size depends on the formation of an organized and uniformly distributed network of blood vessels and capillaries. The lack of such vasculature leads to spatio-temporal gradients in oxygen, nutrients and accumulation of waste products inside engineered tissue constructs resulting in negative biological events at the core of the scaffold. Unavailability of a well-defined vasculature also results in ineffective integration of scaffolds to the host vasculature upon implantation. Arguably, one of the greatest challenges in engineering clinically relevant bone substitutes, therefore, has been the development of vascularized bone scaffolds. Various approaches ranging from peptide and growth factor functionalized biomaterials to hyperporous scaffolds have been proposed to address this problem with reasonable success. An emerging alternative to address this challenge has been the fabrication of pre-vascularized scaffolds by taking advantage of biomanufacturing techniques, such as soft-and photo-lithography or 3D bioprinting, and cell-based approaches, where functional capillaries are engineered in cell-laden scaffolds prior to implantation. These strategies seek to engineer pre-vascularized tissues in vitro, allowing for improved anastomosis with the host vasculature upon implantation, while also improving cell viability and tissue development in vitro. This book chapter provides an overview of recent methods to engineer pre-vascularized scaffolds for bone regeneration. We first review the development of functional blood capillaries in bony structures and discuss controlled delivery of growth factors, co-culture systems, and on-chip studies to engineer vascularized cell-laden biomaterials. Lastly, we review recent studies using microfabrication techniques and 3D printing to engineer pre-vascularized scaffolds for bone tissue engineering.