China3D printingNet September 10th, researchers from the Wyss Institute of Harvard University have developed a new bio-ink book writing technology called SWIFT (Write Function Organization) for3D printingLarge vascularized human organ building block (OBB). The team demonstrated its method, creating heart tissue that merges and beats synchronously within 7 days. This makes it possible to inject into the patient’s organs to achieve a therapeutic effect. The SWIFT biomanufacturing method is very effective in the large-scale creation of organ-specific tissues in OBB from primordial cell aggregates to stem cell-derived organoids.
Reduce transplant wait time through additive manufacturing
According to researchers, in the United States, about 20 people die from organ transplants every day. Although more than 30,000 transplant operations are performed each year, there are currently more than 113,000 patients waiting for organs. In order to solve this organ shortage problem, scientists pin their hopes on artificial organs.
Tissue engineering is a rapidly developing field. 3D printingThe advancement of this technology has led to the prosperity of living tissue structures that use this technology to build the shape of human organs. Organ building blocks composed of organoids derived from patient-specific induced pluripotent stem cells provide a way to obtain tissues with the necessary cell density, microstructure and function. However, so far, little attention has been paid to their assembly into a 3D organizational structure.Through the vascular channel3D printingA living matrix composed of OBB derived from stem cells, the team’s SWIFT technology overcomes this major obstacle and produces living organ-specific tissues with high cell density and function. “This is a brand new organization manufacturing model.” said Dr. Mark Skylar-Scott, a researcher at the Wyss Institute. “It’s not just trying to build a whole cell in 3D, SWIFT’s focus is on biological3D printingA tissue structure that supports life, which contains a large amount of OBBS, which can eventually be used to repair and replace human tissue in a laboratory, containing a growing version of the patient’s own cells. “
Use thin nozzles to simulate organ vasculature, which will consist of a red, branched network of gelatin-based “ink” channels3D printingInto a living heart tissue construct composed of millions of cells (yellow). The photo is from Harvard University’s Wythe School.
SWIFT Biomanufacturing
SWIFT is a two-step biological manufacturing process. First, hundreds of thousands of these OBBs are assembled into a living matrix with high cell density to form a dense OBB life matrix. Containing about 200 million cells per milliliter, the OBB matrix used for SWIFT must also exhibit the desired self-healing viscoplastic behavior.
In the second step, through embedded biology3D printingThe perfusion vascular channel is embedded in the matrix. The constructed blood vessel network allows oxygen and other nutrients to pass through and deliver these important substances to the cells. “Forming a dense matrix from these OBBs does two things with one stone: it can not only achieve high cell density similar to human organs, but the viscosity of the matrix can also print a ubiquitous network of perfusible channels in it to mimic the blood vessels that support human organs. “Added Dr. Sébastien Uzel, who is a research assistant at the Wyss Institute and SEAS.
How to build a beating heart
The cell aggregates used in the SWIFT method are derived from adult induced pluripotent stem cells. Mix with a customized extracellular matrix (ECM) solution to form a viable matrix compacted by centrifugation.
At low temperatures (0-4°C), the dense matrix has the consistency of mayonnaise.Soft enough to operate without damaging the cells, the matrix is still thick enough to maintain its shape,3D printingThe ideal medium. In this technique, a thin nozzle moves through this matrix, depositing a stream of gelatin “ink”, pushing the cells away without damaging them.
When heated to 37°C, the cold substrate gradually hardens and becomes stronger. As the temperature rises, the gelatin ink melts and can be washed off. This leaves a network of channels embedded in the tissue construct, which can be perfused with oxygenated media to nourish the cells. The researchers were able to change the diameter of the channel from 400 microns to 1 mm. 3D printingThe channels can be seamlessly connected to form a network of branch blood vessels within the tissue.
Tissues without SWIFT printed channels show cell death (red) in their core after 12 hours of culture (left), while tissues with channels (right) have healthy cells. The photo is from Harvard University’s Wythe School.
The future of SWIFT therapeutic applications
To determine whether the tissue displays organ-specific functions, the team3D printingAnd perfuse the branch channel structure into a matrix composed of heart-derived cells. After manufacturing the heart-shaped structure, the medium flies through the channel for more than one week. During this period, the heart OBB fuse together to form a stronger heart tissue. The contractions became more synchronized, more than 20 times stronger, mimicking the key characteristics of the human heart.
In the future, the team envisions adopting a new protocol that will provide a way to create a more mature, microvascularized OBB. Collaborating with Wyss Institute faculty, Dr. Chris Chen of Boston University and Dr. Sangeeta Bhatia of Massachusetts Institute of Technology.
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