Biomanufacturing of organ-specific tissues with high cellular density and embedded vascular channels

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.

Nanomaterial Patterning in 3D Printing

“…Indeed, developing the ability to pattern and control nanomaterials in a 3D printing process can enable a multiscale, multimaterial additive manufacturing strategy that can create devices and architecture with unprecedented complexity and functional integration, which has a broad and long‐lasting impact on a wide range of fields—from bioprinting25,50,179,418 to space exploration 419–422…”

From Shape to Function: The Next Step in Bioprinting

“…One possible avenue is to use preformed organoids and embryoid bodies that can be led to self‐assemble and thus to produce tissues with high cell content by jamming them into a mold. These dense cellular structures can then be used as suspended bath to print vasculature within such engineered constructs to ensure organoid viability . Furthermore, hybrid printing strategies can be envisioned, in which part of the construct architecture is imposed by the printing process, and at the same time also rely on the ability of stem cells to self‐organize into polarized and heterocellular constructs.…”

Bioprinting of Multiscaled Hepatic Lobules within a Highly Vascularized Construct

“…To engineer multiscaled heterogeneous tissues and organs, various tissue engineering approaches have been introduced, [ 2 ] specifically 3D bioprinting. [ 3–12 ] Extrusion‐based bioprinting is a promising branch of 3D bioprinting in terms of ease of use, low price, and extensive material selectivity compared to other bioprinting branches (i.e., inkjet bioprinting, laser‐assist bioprinting). [ 13 ] However, the limited printing resolution (100 µm) [ 14 ] is still a bottleneck in the engineering of microscale tissue constructs.…”

“…[ 20 ] In the tissue engineering field, it has been demonstrated that creation of cell‐laden constructs without microchannels decreased cell viability and cellular differentiation compared to pre‐existing microchannels. [ 21 ] Thus, to avoid ischemic conditions, many researchers have utilized sacrificial materials to create microchannels [ 21,22,7,23,11 ] or coaxial nozzles for in situ creation of blood vessels. [ 24–26 ] Further, since capillaries are too small to be printed, a predefined experimental design is essential for interconnection of the microchannels during angiogenesis.…”