Allevi Authors

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

2018-aqueous-two-phase-emulsion-bioink-enabled-3d-bioprinting-of-porous-hydrogels-cover allevi in 3d bioprinter

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

Allevi Author: NJIT Bioprints Vascularized Tissue

NJIT allevi guvendiren vascular vasculature vein 3d bioprint bioprinted bioprinter

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.

HUVEC vascular channel vein 3d bioprinted bioprint allevi NJIT guvendiren

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.

Allevi Author - Valentine's Day Edition: GWU Bioprints Heart Tissue

cardiac muscle myocytes fibroblasts george washington university allevi 3d bioprinters and bionk

George Washington University joins the #AlleviAuthor club with their new paper titled, “Use of GelMA for 3D printing of cardiac myocytes and fibroblasts” and published in Journal of 3D Printing in Medicine.

First let’s review some basics about your heart! Heart tissue is composed of two main cell types; cardiac fibroblasts (CFB) & cardiomyocytes (CMC).

 
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Cardiomyocytes are the contracting cells which allow the heart to pump. Each cardiomyocyte needs to contract in coordination with its neighboring cells to efficiently pump blood from the heart, and if this coordination breaks down then the heart may not pump at all.

Fibroblast cells give support to the muscle tissue. They are unable to provide forceful contractions like cardiomyocytes, but instead are largely responsible for creating and maintaining the extracellular matrix which forms the mortar in which cardiomyocyte bricks are embedded. Fibroblasts also play a crucial role in responding to injury by creating collagen while gently contracting to pull the edges of the injured area together.

In previous academic studies, tests of pure populations of cardiomyoctes have failed to stay viable making it difficult to study the heart in a lab setting. In their recent paper, the team at George Washington University set out to determine how 3D bioprinting affects these two types of cells and if there is a way to create viable 3D tissue in the lab by bioprinting both CMCs and CFBs in tandem.

The team studied the effects of temperature, pressure, bioink composition, and UV exposure to determine the best conditions for 3D bioprinting heart muscle.

Through LIVE/DEAD assays, bioluminescence imaging and morphological assessment, they determined that cell survival within a 3D bioprinted CMC-laden GelMA construct was MORE sensitive to extruder pressure and bioink composition than the fibroblast-laden constructs. Also they determined that BOTH cell types were adversely impacted by the UV curing step. And finally they determined that using a mixture of cardiomyocytess and cardiac fibroblasts increased viability of the tissue- showing that CMCs <3 CFBs.

Cheers to the team at GWU! Their research creates an important foundation for future studies of 3D bioprinted heart tissue.

Read their paper 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.

 
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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: Tohoku University Images Cell Activity in Hyrdrogels

tohoku university allevi bioprinter bioprinted hydrogel imaging

One of the most rewarding “AHA” moments of bioprinting is seeing your cells proliferate within a 3D tissue. As 3D bioprinting becomes more widely adopted within the fields of tissue engineering and personalized medicine, it is important that researchers have the ability to monitor cell activity within in a 3D structure AFTER the print is finished.

Our most recent Allevi Authors have tackled the method of electrochemically monitoring a tissue in their new paper out in the Analytical Sciences Journal titled, “Electrochemical Imaging of Cell Activity in Hydrogels Embedded in Grid-Shaped Polycaprolactone Scaffolds Using a Large-scale Integration (LSI)-based Amperometric Device”.

In their paper, researchers from Tohoku University in Japan use their Allevi 2 bioprinter to print PCL scaffolds as a support material for photocured hydrogels. They then used an amperometric device to electrochemically monitor the living cells. Through their study, they were able to determine that electrochemical imaging is a great way to monitor cell differentiation and will be useful for evaluating the viability of thicker bioprinted tissues.

Congratulations to the Tohoku University researchers on their findings!