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Vascularization is essential for realizing thick and functional tissue constructs that can be utilized for in vitro study platforms and in vivo grafts. The vasculature enables the transport of nutrients, oxygen, and wastes and is also indispensable to organ functional units such as the nephron filtration unit, the blood–air barrier, and the blood–brain barrier. This review aims to discuss the latest progress of organ-like vascularized constructs with specific functionalities and realizations even though they are not yet ready to be used as organ substitutes. First, the human vascular system is briefly introduced and related design considerations for engineering vascularized tissues are discussed. Second, up-to-date creation technologies for vascularized tissues are summarized and classified into the engineering and cellular self-assembly approaches. Third, recent applications ranging from in vitro tissue models, including generic vessel models, tumor models, and different human organ models such as heart, kidneys, liver, lungs, and brain, to prevascularized in vivo grafts for implantation and anastomosis are discussed in detail. The specific design considerations for the aforementioned applications are summarized and future perspectives regarding future clinical applications and commercialization are provided.
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Biomanufacturing of organ-specific tissues with high cellular density and embedded vascular channels
Engineering organ-specific tissues for therapeutic applications is a grand challenge, requiring the fabrication and maintenance of densely cellular constructs composed of ~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.
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- Award ID(s):
- 1647837
- PAR ID:
- 10134061
- Date Published:
- Journal Name:
- Science Advances
- Volume:
- 5
- Issue:
- 9
- ISSN:
- 2375-2548
- Page Range / eLocation ID:
- eaaw2459
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript
- Journal Article:
- https://doi.org/10.1126/sciadv.aaw2459
