Allevi Author: How 3D Bioprinting Solves the Stem Cell Supply Problem

We’ve all read the news stories touting the promise of stem cells to transform the field of regenerative medicine; “The Life Saving Power of Stem Cells”, “The Promise of Stem Cells”, “The $950 Million Dollar Bet on Stem Cells to Cure Diabetes”, etc...

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So why are these cells so exciting to the medical and scientific community? It’s because your stem cells are multipotent - meaning that they have the potential to develop into many different cells in the body. Because they have this ability to reprogram (or ‘differentiate’), stem cells can be used to repair diseased or damaged tissue in humans.

However, these promising therapies require a large number of stem cells for a single treatment (up to one billion cells may be needed just for one patient) and manufacturing these special cells is challenging. Traditional two-dimensional culture protocols are resource-intensive and inefficient - making it difficult to scale the production to meet future demands.

Our newest Allevi Authors are working on an innovative new approach to solving the stem cell supply problem and have detailed their research in a paper titled, “Bioprinting of Stem Cell Expansion Lattices”.

The team of scientists, led by Stanford Professor Sarah Heilshorn, developed an easy-to-produce and cost-effective 3D platform for cell line expansion by bioprinting stem cells in a layered lattice structure. Using their Allevi 2 bioprinter, the team created three-dimensional lattice structures of stem cells and alginate that reduce the spatial footprint, energy, and resources needed to multiply the cells. So why is this method optimal? Imagine that you are a city planner with a limited amount of space to build more housing, you would be able to provide homes for more residents by building high-rises rather than individual houses.

 
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Using alginate and an Allevi bioprinter, the team is able to create 3D structures that provide a healthy environment for the cells to grow without taking up too much space or using too many resources. Most importantly, the team was able to efficiently remove the stem cells from the lattices without harming the cells.

With countless stem-cell therapies in development for numerous diseases, researchers and doctors are going to need a large number of stem cells in order to bring their work to fruition. This forward-looking approach to solving the supply problem provides a path to clinical applications for patients looking to receive one of these novel therapies in the future.

Read the full paper here.

Allevi Author: Brigham & Women's Hospital Proves Porous is Preferred

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We’re so excited to welcome the Yu Shrike Zhang lab from Brigham & Women’s Hospital to the Allevi Author Club!

3D bioprinting is an amazing technology which allows researchers to create custom cell-laden constructs that mimic the human body better than their 2D counterparts. Here at Allevi, our mission is to make it easy for scientists to replicate the body outside the body. Our community of users is composed of the leadings minds in tissue engineering and they are working on every type of tissue from brain to bone.

Agnostic of tissue type, one of most important aspects of 3d bioprinting is ensuring that your cells organize and proliferate as they would in your body. Bioinks provide cells with a much needed support that allows them to more easily organize into the geometries that they would in native tissue. However, if a bioink is too dense or too rigid, it can actually hinder the proliferation of cells and prevent them from performing their needed function.

Our new #AlleviAuthors tackled this problem in their new paper titled “Aqueous Two‐Phase Emulsion Bioink‐Enabled 3D Bioprinting of Porous Hydrogels” and published in Advanced Materials.

By creating an aqueous bioink emulsion, the researchers were able to create a construct that is porous in composition while at the same time providing the rigidity needed in order to create 3D constructs. Their bioink is composed of cells mixed with GelMA and PEO which are immiscible materials - meaning that they do not mix in a homogenous manner. A classic example of immiscible liquids is oil and water. The fact that GelMA and PEO naturally repel each other means that small droplets of each material exist side by side within the bioink.

Using the Allevi 2 bioprinters, this bioink was bioprinted and crosslinked to form the desired geometry and rigidity of the tissue type that you are recreating. After the desired geometry has been achieved, you are then able to remove the PEO from the construct leaving small holes in the structure that allow cells to proliferate with greater ease.

The researchers tested their new method across 3 different cell lines and found that the porous 3D-bioprinted hydrogels showed enhanced cell viability and proliferation vs nonporous hydrogels. This new method means that researchers across any tissue type are now able to create porous-structures with higher cell viability. We’re excited to see the FAR reaching effects of this method for our entire community of Allevi researchers!

Read on to learn more about their novel bioink and how to incorporate it into your research: https://onlinelibrary.wiley.com/doi/full/10.1002/adma.201805460

3D Bioprinting Replacement Heart Valves

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Throwing it back today to show you this heart valve that was 3d bioprinted using the Allevi 2 with collagen from Advanced BioMatrix.

Your heart has four valves (one for each chamber) that are made up of thin flaps of tissue called cusps. These flaps open and close to allow blood to move through the heart while beating.  The cusps attach to an outer ring of tougher tissue called the annulus. The annulus helps the valve maintain proper shape under the normal strains and stresses of a heartbeat. 

 
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It is essential that your valves open and close tightly to ensure proper blood flow through the heart and onto the rest of your body. A diseased or damaged valve can give you an irregular heartbeat and eventually lead to heart failure. More than 5 million Americans are diagnosed with heart valve disease every year.

 
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Many people can live with valve disease and do not require surgery. However, in some cases, the valve needs to be fixed or replaced. Current methods for replacing a damaged valve included plastic parts or animal tissues.

Allevi users are working towards a future where your #doctor is able to 3d bioprint a custom replacement valve from your own heart cells to reduce the rate of failure and rejection. 3D bioprinting is an amazing design tool that allows you to print custom geometries and tune the rheological properties to provide your cells with the support structure they need to do their job. Just another amazing way our users are changing the future of medicine. #buildwithlife #healwithlife

Allevi Author: NJIT Bioprints Vascularized Tissue

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We are VERY excited to announce the latest addition the Allevi Author Club; the Guvendiren Lab from the New Jersey Institute of Technology.

Dr. Guvendiren’s lab focuses on creating novel bioinks for tissue engineering and regenerative medicine applications with a focus on 3D bioprinting. Their most recent paper, published in Acta Biomaterialia and titled “3D bioprinting of complex channels within cell-laden hydrogels”, explores their new approach to 3D bioprinting vasculature into 3D tissue.

There are many different methods for creating microchannels within constructs, including electrospinning, fiber bonding, and casting solvents into molds. However these techniques don’t allow for precise control of channel size, shape or location. They can also be time-consuming and restrictive in the number of cell lines that you are able to work with simultaneously.

The Guvendiren lab is exploring a new approach to creating these channel-laden tissues using their Allevi 2 bioprinter. In their paper, they explore a method of 3D bioprinting sacrificial bioinks into cell-laden hydrogels (pluronic into methacrylated alginate/methacrylated hyaluronic acid to be specific). This technique allows them to create custom channel geometries, control channel thickness and tune the hydrogel rigidity. They also explored a super cool technique wherein they alter the printhead speed in order to create channels of differing diameters.

Their images from confocal scanning show strong endothelial cell (HUVEC) attachment to the channel walls and depict the final 3D bioprinted vein construct.

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This research explores important techniques for creating tunable microchannels within 3D tissues. We can imagine a future wherein these methods are used to create 3D bioprinted organs with custom and complex vascular networks. It could also be used to create custom 3D models to study disease progression and test drug efficacy and toxicity. Amazing work, Guvendiren Lab!!

Click through to read their material characterization and learn more about their bioprinting approach: https://www.sciencedirect.com/science/article/pii/S1742706119301515.

Introducing: The Allevi Tissue Layering Bioink Kit

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Your cells are smart. They know the forces around them, what materials they are in, and can even sense the smallest details in a bioink. Have you ever wondered how pure your bioinks are? Do they contain any thickening agents that can negatively affect tissue viability and function? It’s worth a look at the data sheet the next time you consider using a new bioink in lab.

Here at Allevi, we take great strides to source the purest bioinks that are most commonly found in our bodies. The collagens we choose provide unparalleled results that biologists and bioengineers love. There is a challenge in doing this though; pure collagen has historically been a very difficult bioink to work with because it is difficult to pattern. Low concentrations of collagen (like the concentration found in your body) have a very low viscosity, making it hard to control the geometry of the tissue and hindering cell directed proliferation.

We have been working in our lab for over a year trying to crack the code on low concentration collagen bioprinting. So much amazing research has already been conducted with collagen that we wanted to make it easy for you to bring that research to the next level with 3D bioprinting.

We’re proud to announce that we have finally achieved the ability to pattern pure collagen in an automated fashion. With our proprietary CORE™ printhead and our new Tissue Layering Kit, you are now able to print and pattern 3 mg/mL type I collagen or 8 mg/mL type I methacrylated collagen. This is the first time that such low concentrations of pure collagen can be printed, patterned, and layered through 3D bioprinting. We can’t wait to see what you will do with this one!

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