A new 3D printing paradigm
Every day in the United States, 20 people die without waiting for an organ for transplantation. And although more than 30,000 transplants are performed annually, there are currently more than 113,000 patients on waiting lists in this country. Artificially grown organs of the human body are considered by many as the main alternative to cadaveric organs, and advances in three-dimensional printing have led to the active development of this technique for creating tissues and organs. However, to date, no human 3D tissue has sufficient cell density and is not able to perform functions at the level necessary for use in the restoration and replacement of organs.
A group of researchers from the Wyss Institute of Harvard University and the Harvard School of Engineering and Applied Sciences. John A. Paulson (John A. Paulson School of Engineering and Applied Sciences, SEAS) has developed a new technique for removable printing into functional tissue (Sacrificial Writing Into Functional Tissue, SWIFT).
SWIFT consists in 3D printing of vascular channels in living matrices consisting of structural blocks of organs derived from stem cells. As a result, viable organ-specific tissues with high cellular density and functionality are obtained.
Live embryoid corpuscles surrounding a hollow vascular canal printed by SWIFT. Source here and further: Wyss Institute at Harvard University.
In other words, instead of printing the matrix of an entire organ, SWIFT focuses only on printing the vessels necessary to maintain the structure of living tissue containing a large number of structural blocks from patients' own cells.
The SWIFT technique consists of two stages. The process begins with the formation of a dense living matrix (structural blocks) from hundreds of thousands of stem cell aggregates, which contains about 200 million cells in one milliliter. Then, a vascular network is introduced into the matrix by printing and removing ink, through which oxygen and other nutrients will be delivered to the cells. The formation of structural blocks allows you to kill two birds with one stone: a high density of cells is achieved, akin to human organs, and the necessary viscosity of the matrix, which allows you to print a wide network of penetrating channels (future blood vessels) in it.
The SWIFT bioprinting process: forming dense structural blocks from living cells, printing and removing gelatin ink and creating heart tissue that contracts like a living heart within seven days.
The cell aggregates used in the SWIFT method are obtained from adult induced pluripotent stem cells added to a solution of a specially developed extracellular matrix to produce a living structure that is compacted by centrifugation. At low temperatures (0-4°C), the dense matrix has the consistency of mayonnaise – soft enough to be manipulated in it without damaging cells, but dense enough to retain its shape. This makes it an ideal medium for three-dimensional vessel printing.
During printing, a thin nozzle moves through the living matrix, leaving a thread of gelatin "ink" that pushes the cells apart without damaging them.
An extensive network of channels made of gelatin ink (red) during 3D printing in living heart tissue consisting of millions of cells (yellow), using a thin nozzle.
When the cold matrix is heated to 37°C, it becomes solid, and the gelatin ink melts and can be removed. In their place, there remains a network of channels in the thickness of the tissue structure, into which an oxygen-saturated medium can be injected to nourish cells. The diameter of the channels can vary from 400 micrometers to 1 millimeter, the channels can be smoothly connected, forming branched vascular networks in the tissues.
In tissues created without channels, cell death begins (red) in the center 12 hours after cultivation (left), whereas in tissues with SWIFT channels (right), cells are healthy.
Organ-specific tissues that were printed using SWIFT and perfused with a nutrient medium remained viable, while tissue cells without these channels died within 12 hours.
To see if SWIFT tissues perform organ-specific functions, the team created blocks with channels containing heart cells. Perfusion through these channels for more than a week led to the fusion of structural blocks and the formation of stronger cardiac tissue, which contracted relatively synchronously and quite strongly, imitating the key features of the human heart.
Bio-production by SWIFT method is very promising for the creation of organ-specific tissues. The authors managed to achieve such success thanks to the integration of the latest achievements in stem cell work and bioprinting methods developed in the laboratory of Harvard University.
The group is currently collaborating with colleagues from Boston University and the Massachusetts Institute of Technology to test on animal models and evaluate the integration of SWIFT tissues with a living organism.
Article by M. A. Skylar-Scott et al. Biomanufacturing of organ-specific tissues with high cellular density and embedded vascular channels is published in the journal Science Advances.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the Wyss Institute: A swifter way towards 3D-printed organs.