Biomanufacturing of organ-specific tissues with high cellular density and embedded vascular channels
Top Cited Papers
Open Access
- 6 September 2019
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Advances
- Vol. 5 (9), eaaw2459
- https://doi.org/10.1126/sciadv.aaw2459
Abstract
Engineering organ-specific tissues for therapeutic applications is a grand challenge, requiring the fabrication and maintenance of densely cellular constructs composed of ~108 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.Keywords
Funding Information
- Office of Naval Research (N000141612823)
- National Human Genome Research Institute (RM1HG008525)
- GETTYLAB
This publication has 30 references indexed in Scilit:
- Multivascular networks and functional intravascular topologies within biocompatible hydrogelsScience, 2019
- In situ expansion of engineered human liver tissue in a mouse model of chronic liver diseaseScience Translational Medicine, 2017
- An integrated design and fabrication strategy for entirely soft, autonomous robotsNature, 2016
- Engineering Stem Cell OrganoidsCell Stem Cell, 2016
- Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesisNature, 2015
- Writing in the granular gel mediumScience Advances, 2015
- The Billion Cell Construct: Will Three-Dimensional Printing Get Us There?PLoS Biology, 2014
- Biomimetic engineered muscle with capacity for vascular integration and functional maturation in vivoProceedings of the National Academy of Sciences of the United States of America, 2014
- Vascularized and functional human liver from an iPSC-derived organ bud transplantNature, 2013
- Engineered heart tissue grafts improve systolic and diastolic function in infarcted rat heartsNature Medicine, 2006