New Findings

Newly Formulated Cell Media Will Change the Way We Study Cancer

cell culture media bioprint bioprinter

The first synthetic cell culture medium was formulated 60 years ago by an American physician named Harry Eagle. As a pathologist, Dr. Eagle needed a way to keep cells alive longer in a laboratory setting in order to study their growth and behavior. His formula, better known at EMEM (Eagle's minimal essential medium), is composed of a mixture of sugars, vitamins, salts, and amino acids and as its name implies, is the bare minimum of nutrients needed in order to keep cells alive ex-vivo.

Since its creation, Eagle’s medium has become an essential consumable in labs worldwide where it is used by researchers to study animal cells. However, the formulation hasn’t changed much since making its debut in 1959 and recently scientists have begun to wonder if feeding cells the bare minimum of nutrients is skewing the results they are obtaining in lab.

Thinking of EMEM as Gatorade (which it essentially is), you can imagine what would happen if you tried to subsist on a diet of Gatorade alone. Your body wouldn’t behave normally under such harsh conditions so why do we expect your cells to be any different?

In 2012, a researcher by the name of Saverio Tardito set out to create a more relevant cell medium.

“The vast majority of biomedical researchers use cell culture media that were not designed to reproduce the physiological cellular environment but were formulated to enable the continued culture of cells with minimal amounts of nutrients and serum”.

Improving the metabolic fidelity of cancer models with a physiological cell culture medium, Science Advances

His final concoction, called Plasmax, is a mixture of approximately 60 nutrients and metabolites found in the human blood. In their paper, published in Science Advances, Tardito and his colleagues at Cancer Research UK Beatson Institute compared Plasmax with traditional cell culture media and found that cells cultured in Plasmax behaved in a more physiological manner.

By studying Plasmax in conjunction with cancer cells, Tardito and his team concluded that their newly formulated medium can improve the degree to which in-vitro models behave as they would in-vivo and ultimately provide better models for cancer research.

As we enter the renaissance of tissue engineering, we are deepening our understanding of the complex organisms that make up the human body. In order to develop novel drugs, better study disease, and regenerate tissue, it is imperative that we develop more relevant models in the lab that mimic the geometry, environment and diet that cells exist on in the body.

Read the full article here.

Allevi Author: 3D‐Printed Sugar Stents to Aid in Surgery

Microvascular anastomosis (or the method of surgically connecting blood vessels) is a common part of many reconstructive and transplant surgical procedures.

There are multiple methods for connecting two veins together including coupling devices, surgical glue, and surgical suturing but each method has it’s downsides; coupling devices can face rejection from the body, glue can introduce contamination or clotting to the vein, and suturing (the most commonly accepted practice) is a delicate and time consuming procedure.

 
suturing blood vessels
 

During the suturing procedure, surgeons are in a race against the clock to quickly connect the veins together to ensure that organs continue to receive proper blood flow. However, blood vessels of differing shapes and sizes can sometimes make this procedure difficult to maneuver in a timely fashion.

 
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In their recent paper titled, “3D‐Printed Sugar‐Based Stents Facilitating Vascular Anastomosis”, researchers at Brigham and Women’s Hospital & The University of Nebraska Lincoln collaborated using an Allevi 2 bioprinter to find a solution to aid in the intricacies surrounding this procedure.

Here, dissolvable sugar‐based stents are 3D printed as an assistive tool for facilitating surgical anastomosis. The non-brittle sugar‐based stent holds the vessels together during the procedure and are dissolved upon the restoration of the blood flow. The incorporation of sodium citrate minimizes the chance of thrombosis, and the dissolution rate of the sugar‐based stent can be tailored between 4 and 8 min.

 
allevi 2 3d bioprinter fabricates sugar stents to aid in surgical procedure
 

3D printing is an ideal method for constructing these stents because you are able to quickly design and create custom geometries to fit the patient’s vessels.

The effectiveness of the printed sugar‐based stent was assessed ex vivo and found to be a fast and reliable fabrication method that can be performed in the operating room.

This new method of aiding surgeons is a game-changer as it is dissolvable, tunable, and completely customizable. In the future, your doctor could quickly print out stents to match your exact vein geometry which would reduce the time spent on the operating table and under anesthesia.

Interested in learning more about this novel technique? You can read the full paper here: https://onlinelibrary.wiley.com/doi/abs/10.1002/adhm.201800702?af=R&

Allevi Author: Lattices vs Sheets for Cardiac Tissue Bioprinting

There are so many variables that go into creating viable 3d bioprinted tissues; bioink selection, print geometry, cure times, rigidity, flexibility, degradation time and cell viability to name a few. Not to mention, each of these parameters needs to be analyzed and perfected for every cell line in the body. As a community, we are still figuring out the perfect protocol for each organ system.

In a new paper out this week titled “A Comparative Study of a 3D Bioprinted Gelatin-Based Lattice and Rectangular-Sheet Structures”, our newest Allevi Authors tackled one of these lingering questions, “What is the best print structure for cardiac tissue, lattice or sheet?”

Researchers at University of Texas El Paso and University of Texas at Austin used their Allevi 2 bioprinter and furfuryl gelatin to study and compare 3d bioprinted lattices vs sheets. Through their comparison, they discovered that the lattice structure was more porous with enhanced rheological properties and exhibited a lower degradation rate compared to the rectangular-sheet.

Further, the lattice allowed cells to proliferate to a greater extent compared to the rectangular-sheet. All of these results collectively affirmed that the lattice poses as a superior scaffold design for tissue engineering applications.

Read the full paper here to learn more about the rigorous testing and analysis the team conducted during their study.

Allevi Bioprinting in Space

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The physical exploration of space began in the 1950s with the race between the Soviet Union and the United States for who could take those weightless first steps.  Orbiting above earth, astronauts have since made countless discoveries of the galaxy we live in and the science of the stars. On top of the celestial research, space exploration has yielded humanity practical tools that improve our daily lives, such as the GPS in your car, the ear thermometer in your medicine cabinet, and the joystick on your gaming console. Without the constraints of gravity, astronauts are able to study and innovate in a truly novel way.

As we continue to explore deeper into space, astronauts are spending more time in orbit than ever before and need tools that are adaptable and customizable for any given task. This is the ethos behind Made in Space, an organization that focuses on increasing human capability in orbit by bringing 3d printing technology onto the International Space Station (ISS). Accessibility to 3D printing on the ISS has allowed astronauts to print custom plastic tools and parts that are needed to successfully achieve their mission. No need to come back to earth to fetch that tool, you can now print it at zero g.

Here at Allevi, we are driven by the goal of being able to 3D bioprint replacement organs for humans. While we continue to understand the capabilities and constraints of 3d biofabrication here on Earth, the ability to explore cellular function in space could afford us novel discoveries of organ form and function that have never before been studied.

Allevi zeroG bioprinting in space on ISS

In pursuit of this novel research, we have partnered with Made in Space to develop the first bioprinter in space; the Allevi ZeroG. We have designed a compatible extruder that can be outfitted onto Made In Space’s existing Additive Manufacturing Facility on the ISS. The ZeroG bio-extruder will allow scientists on the Allevi platform to simultaneously run experiments both on the ground and in space to observe biological differences that occur with and without gravity.

We are excited to continue to revolutionize how we study biology, not only on the ground but now in space. And perhaps one day, the Allevi ZeroG will aid astronauts in 3D bioprinting replacement organs for deep space travel. We’re excited to participate in this next generation space race.

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allevi zerog bioprinting in space

The Challenges and Advances of Imitating Nature

Allevi Advanced Biomatrix additives bioink additives for 3d bioprinting tissue and organs on 3d bioprinter

One of the largest hurdles of in vitro cell culture has been to mimic conditions that closely resemble in vivo outcomes. Significant strides have been made to this end in the past decades with progress accelerating in more recent years.

One approach that has widely-contributed to progress in tissue engineering and regenerative medicine has been to imitate the human body as accurately as possible. Tissues and organs consist of a milieu of extracellular matrices with varying quantities and placements.

With the advances in 3D bioprinting, scientists now have another tool to move closer to engineering tissues and organs that are more in vivo-like. Employing 3D bioprinting, a variety of ECMs can be precisely deposited in more native formats. 3D bioprinters now have multiple dispensing heads that can simultaneously lay down the ECM with cells in tissue and organ-like configurations. Furthermore, discoveries have recently been made creating native bioinks that are compatible with 3D bioprinters. A combination of such advances and discoveries with 3D bioprinters and native ECM bioinks likely propel future advancements in tissue and organ fabrication.

Further, native collagen bioinks consisting of Type I collagen can also be blended with other ECM’s to formulate more in vivo-like bioinks. Some of these ECMs include Type I, II, III, IV, V collagens, hyaluronic acid, elastin (tropoelastin), fibronectin and vitronectin. ECMs play a major role in achieving the proper cell behavior, cell adhesion signals and binding sites.

In addition to formulating a more optimal ECM environment, cells can be pre-mixed with the bioinks and bioprinted. The cells, in many cases, have been shown to remodel the tissue. Cells secrete and deposit their own intrinsic ECMs, growth factors, cytokines and other biologically relevant components.

The combination of these advanced 3D bioprinters, and cell-laden yet native-to-the-body bioinks, greatly enhance the capabilities and tools available to tissue engineers and scientists.

Allevi is excited to begin offering a broad line of native extracellular matrix proteins from Advanced BioMatrix (ABM) to serve as additives to many of Allevi’s BioInks. Bowman Bagley, Director of Business Development at ABM, comments: “The bar is being raised each day as new publications come out. Researchers are beginning to reject non-native materials as new native, yet printable, bioinks have emerged and are commercially available. The quest to bioprint tissues and organs begins with bioinks composed of native proteins that best replicate a natural, in vivo-like cellular environment. Our goal is to provide all of the proteins that help best replicate the human body when bioprinting. To print native tissues, we need native bioinks.”

As we continue to try and control tissue design, Allevi continues to provide the tools that will allow scientist to most accurately represent human architecture.