来自Harvard University’sWyss Institute已经开发了一套新的心脏工程技术，使他们能够模仿人心的收缩元素的对齐。
利用含有收缩器官的生物焦点（OBB）和患者特异性干细胞，该团队能够生物板的心脏组织，具有复杂而多样的比对，类似于实际人体心肌层。
In the future, the team’s advance could enable the development of thick multi-layered human muscle tissue with more physiological contractile properties and, potentially, pave the way toward 3D printed heart tissue replacements.
“Being able to effectively mimic the alignment of the heart’s contractile system across its entire hierarchy from individual cells to thicker cardiac tissue composed of multiple layers is central to generating functional heart tissue for replacement therapy,” said Jennifer Lewis, senior author of the study and Wyss Core Faculty member.
迅速生物打印平台
The Wyss Institute has been developing innovative bioprinting technologies and tissue engineering techniques for a number of years. For instance, in February, bioengineering start-up栈桥生物治疗学licensed a Harvard University-developed technology that enables therapid fabrication of kidney tissuesat scale.
The team has been looking into bioprinting heart tissue for some time, having created a 3D printing workflow to预测人造心脏瓣膜的性能back in 2018. A year later, the scientists developed their novel牺牲墨水编写技术称为Swift（牺牲在功能组织中）至3D打印大型血管化的人类OBB。
The team was able to create cardiac tissue that fuses and beats synchronously over a seven-day period, and has expanded upon this achievement in its latest study.
Bioprinting human heart muscle
The Wyss Institute team’s latest study builds on its SWIFT bioprinting platform. The approach makes use of preassembled OBBs made from human induced pluripotent stem cells (hiPSCs-CMs) to produce blood-supporting vascular networks using sacrificial inks. Using the platform’s sophisticated 3D bioprinting capabilities, the scientists were able to create cardiac tissue constructs that have the typical high cellular densities of normal heart tissue.
“To also gain control over directional contractility in engineered layers of heart tissue, we first devised a strategy to program the parallel alignment of iPSC-CMs in developing OBBs,” said first-author John Ahrens, who is a graduate student in Lewis’ group.
To create the cell-laden bioink, the team developed a platform with 1050 wells that each contain two micropillars. They then seeded hiPSCs-CMs into the wells via a mixture containing human fibroblast cells and the extracellular matrix (ECM) protein collagen, both of which are essential for heart muscle development.
As the cells compact the ECM, they formed a dense microtissue within which the cardiomyocytes and their cellular contractile machineries were oriented along the axis connecting the micropillars. The OBBs, capable of contracting in one major direction, were then lifted off the micropillars and used as feedstock for the bioprinting process.
“我们的实验室以前已经表明，可以通过3D打印对齐各向异性软材料，”研究合着者Sebastien Uzel说。“在这里，我们证明了这一原理也可以应用于心脏微动物。”
To demonstrate their technique, the scientists 3D bioprinted cardiac tissue sheets with linear, spiral, and chevron geometries within which the OBBs showed significant alignment.
Evaluating the 3D printed heart muscle
一旦载有OBB的心脏组织层，该团队就试图测量构建体的收缩特征。研究人员3D打印了连接两个大型大型的长长丝，采用类似但更大的方法，用于在生物墨水配方过程中为OBB生成步骤。
The team was able to measure the macropillar deflections to determine the contractile forces generated by the macrofilaments, and found that the tissues’ contractile forces and contraction speed increased over a seven-day period. Simply put, the 3D printed tissues continued to mature into actual muscle-like filaments.
乌泽尔说：“迅速，我们想解决细胞密度和组织尺度。”“现在，通过编程对齐，我们旨在模仿心肌的微体系结构。一次创新，我们正靠近工程功能性心脏组织进行修复或更换。”
Going forwards, the team is planning to apply their method to fabricate more physiological tissues beyond single-layered constructs.
“While the holy grail of tissue engineering efforts would be a whole organ heart transplantation, our approach could enable contributions to more immediate applications,” added Ahrens. “It could be used to generate more physiological disease models, and create highly architected myocardial patches that, like LEGO blocks, could match and be used to replace a patient-specific scar after a heart attack. Similarly, they could be tailored to patch up patient-specific holes in the heart of newborns with congenital heart defects.
“从理论上讲，这些补丁也可以随孩子而发展，而不必随着孩子的成长而被取代。”
Further information on the study can be found in the paper titled:“通过生物打印各向异性器官构建块编程在工程心脏组织中的细胞对齐，”published in the Advanced Materials journal. The study is co-authored by J. Ahrens, S. Uzel, M. Skylar-Scott, M. Mata, A. Lu, K. Kroll, and J. Lewis.
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Featured image shows生物打印长的心脏大丝来测量收缩心肌层引起的大型偏转。图像通过哈佛大学。
