Barabaschi Giada D G, Manoharan Vijayan, Li Qing, Bertassoni Luiz E
Department of Aerospace, Mechanical and Mechatronic Engineering, University of Sydney, Sydney, NSW, Australia.
Bioengineering Laboratory, Faculty of Dentistry, University of Sydney, Sydney, NSW, Australia.
Adv Exp Med Biol. 2015;881:79-94. doi: 10.1007/978-3-319-22345-2_5.
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 hyper-porous 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.
具有临床相关尺寸的功能性组织构建体的存活取决于形成有组织且分布均匀的血管和毛细血管网络。缺乏这种脉管系统会导致工程化组织构建体内氧气、营养物质出现时空梯度以及废物积累，从而在支架核心引发负面生物学事件。定义明确的脉管系统的缺失还会导致支架在植入后与宿主脉管系统的整合无效。因此，可以说在工程化具有临床相关性的骨替代物方面，最大的挑战之一就是开发血管化骨支架。从肽和生长因子功能化生物材料到高孔隙率支架，人们提出了各种方法来解决这个问题，并取得了一定的成功。应对这一挑战的一种新兴替代方法是利用生物制造技术（如软光刻和光光刻或3D生物打印）以及基于细胞的方法来制造预血管化支架，即在植入前在载有细胞的支架中构建功能性毛细血管。这些策略旨在体外构建预血管化组织，以便在植入时改善与宿主脉管系统的吻合，同时还能提高体外细胞活力和组织发育。本章将概述近期用于骨再生的预血管化支架工程方法。我们首先回顾骨结构中功能性毛细血管的发育，并讨论生长因子的可控递送、共培养系统以及用于工程化载有血管化细胞的生物材料的芯片研究。最后，我们回顾近期利用微制造技术和3D打印来工程化用于骨组织工程的预血管化支架的研究。
