Department of Finemechanics, Graduate School of Engineering, Tohoku University, 6-6-01 Aramaki, Aoba-ku, Sendai 980-8579, Japan.
Lab Chip. 2017 Dec 5;17(24):4186-4219. doi: 10.1039/c7lc00774d.
Angiogenesis plays an important role not only in the growth and regeneration of tissues in humans but also in pathological conditions such as inflammation, degenerative disease and the formation of tumors. Angiogenesis is also vital in thick engineered tissues and constructs, such as those for the heart and bone, as these can face difficulties in successful implantation if they are insufficiently vascularized or unable to connect to the host vasculature. Considerable research has been carried out on angiogenic processes using a variety of approaches. Pathological angiogenesis has been analyzed at the cellular level through investigation of cell migration and interactions, modeling tissue level interactions between engineered blood vessels and whole organs, and elucidating signaling pathways involved in different angiogenic stimuli. Approaches to regenerative angiogenesis in ischemic tissues or wound repair focus on the vascularization of tissues, which can be broadly classified into two categories: scaffolds to direct and facilitate tissue growth and targeted delivery of genes, cells, growth factors or drugs that promote the regeneration. With technological advancement, models have been designed and fabricated to recapitulate the innate microenvironment. Moreover, engineered constructs provide not only a scaffold for tissue ingrowth but a reservoir of agents that can be controllably released for therapeutic purposes. This review summarizes the current approaches for modeling pathological and regenerative angiogenesis in the context of micro-/nanotechnology and seeks to bridge these two seemingly distant aspects of angiogenesis. The ultimate aim is to provide insights and advances from various models in the realm of angiogenesis studies that can be applied to clinical situations.
血管生成不仅在人类组织的生长和再生中起着重要作用，而且在炎症、退行性疾病和肿瘤形成等病理条件下也是如此。血管生成对于厚工程组织和结构物（如心脏和骨骼）的形成也至关重要，因为如果这些组织或结构物血管化不足或无法与宿主血管系统连接，它们在成功植入时可能会面临困难。已经使用各种方法对血管生成过程进行了大量研究。通过研究细胞迁移和相互作用、模拟工程血管与整个器官之间的组织水平相互作用以及阐明不同血管生成刺激物涉及的信号通路，对病理性血管生成进行了细胞水平的分析。针对缺血组织或伤口修复的再生血管生成方法侧重于组织的血管化，可以将其大致分为两类：指导和促进组织生长的支架，以及靶向输送基因、细胞、生长因子或药物以促进再生的方法。随着技术的进步，已经设计和制造了模型来再现固有微环境。此外，工程结构物不仅为组织向内生长提供了支架，而且还为可以用于治疗目的的药物提供了储存库，可以进行可控释放。这篇综述总结了微/纳米技术背景下病理性和再生血管生成建模的当前方法，并试图弥合血管生成这两个看似遥远的方面。最终目标是为血管生成研究领域的各种模型提供见解和进展，这些模型可以应用于临床情况。
