Biomanufacturing of organ-specific tissues with high cellular density and embedded vascular channels
Biomanufacturing of organ-specific tissues with high cellular density and embedded vascular channels
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DOI：
10.1126/sciadv.aaw2459
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发表时间：
2019-09-01
期刊：
影响因子：
13.6
通讯作者：
Lewis, Jennifer A.
中科院分区：
文献类型：
--
作者：
Skylar-Scott, Mark A.;Uzel, Sebastien G. M.;Lewis, Jennifer A.
用于治疗应用的工程化器官特异性组织是一个巨大的挑战，需要制造和维持由类似于10（8）个细胞/ml组成的密集细胞构建体。由患者特异性诱导的多能干细胞衍生的类器官组成的器官构建块（OBB）提供了实现具有必要的细胞密度、微结构和功能的组织的途径。然而，迄今为止，很少有人关注它们组装成3D组织构建体。在这里，我们报告了一种生物制造方法，用于将数十万这些OBB组装成具有高细胞密度的活基质，通过嵌入式三维生物打印将可灌注的血管通道引入其中。OBB基质表现出牺牲写入功能组织（SWIFT）所需的期望的自愈、粘塑性行为。作为一个范例，我们创建了一个可灌注的心脏组织，在7天的时间内同步融合和跳动。我们的SWIFT生物制造方法能够以治疗规模快速组装可灌注的患者和器官特异性组织。
Engineering organ-specific tissues for therapeutic applications is a grand challenge, requiring the fabrication and maintenance of densely cellular constructs composed of similar to 10(8) cells/ml. Organ building blocks (OBBs) composed of patient-specific-induced pluripotent stem cell-derived organoids offer a pathway to achieving tissues with the requisite cellular density, microarchitecture, and function. However, to date, scant attention has been devoted to their assembly into 3D tissue constructs. Here, we report a biomanufacturing method for assembling hundreds of thousands of these OBBs into living matrices with high cellular density into which perfusable vascular channels are introduced via embedded three-dimensional bioprinting. The OBB matrices exhibit the desired self-healing, viscoplastic behavior required for sacrificial writing into functional tissue (SWIFT). As an exemplar, we created a perfusable cardiac tissue that fuses and beats synchronously over a 7-day period. Our SWIFT biomanufacturing method enables the rapid assembly of perfusable patient- and organ-specific tissues at therapeutic scales.