Interview: BIOLIFE4D is The First US Company to Bioprint a Mini-Heart (for Cardiotoxicity Testing)
After quite a few teaser pictures on their social media platforms since August, BIOLIFE4D finally announced one of the biggest milestones for the company: they successfully 3D printed a tiny heart. But how small is the mini heart? Actually, it is about one quarter the size of a human heart.
The ability to 3D bioprint a mini-heart now gives the biotech firm a roadmap to achieve their ultimate goal: bioprinting a full-scale human heart viable for transplant. It is now a matter of optimizing processes and scaling up the technology for the pioneering company headquartered in Illinois.
With the structure of a full-sized heart and four internal chambers, the mini heart is replicating partial functional metrics compared to a full-sized heart – as close as anyone has gotten to producing a fully functional heart through 3D bioprinting. The scientific milestone was accomplished at the company’s research facility at JLABS in Houston, led by Ravi Birla, Chief Science Officer of BIOLIFE4D
3DPrint.com asked Birla about their achievement to understand how functional it is and how this project could lead to a fully beating organ in the future.
“The functional performance of our mini-heart is not the same as a normal mammalian heart, though this is a future objective of the research,” explained Birla. “Our mini-heart is intended for use in drug cardiotoxicity screening, which means that the bar that it must achieve is less than the bar required for a viable transplanted organ. This is why the performance requirements for our mini-heart do not need to mimic a fully-functional animal heart at this point.”
“As we move forward we will be optimizing our bioink as well as the bioprinting parameters which are needed for optimal functional performance,” suggested the expert, who also previously served as the Associate Director of the Department of Stem Cell Engineering at the Texas Heart Institute in Houston.
So how did they do it? First on their list was developing a proprietary bioink using a very specific composition of different extracellular matrix compounds that closely replicate the properties of the mammalian heart. There is still no formal name to the bioink as it was developed in-house and for now, it is currently intended for BIOLIFE4D use only.
Then, they got around creating a novel and unique bioprinting algorithm, consisting of printing parameters optimized for the whole heart. Coupling its proprietary bioink with patient-derived cardiomyocytes and its enabling bioprinting technology, BIOLIFE4D was able to bioprint a heart. Birla suggested that because of the strategic partnerships that they have developed, they have access to and utilize most of the commercially available printers which are on the market, but the mini-heart was essentially biofabricated in their labs using a CELLINK INKREDIBLE+.
“We currently used a commercial source of human cells, through the expected use of the technology in using patient derived autologous cells,” claimed Birla. “Utilizing patient specific cells is really a cornerstone to our technology.”
“Currently those lucky enough to receive a donor heart transplant are really only trading one disease for another. The donor heart will save their life, but to prevent rejection the patient needs to take a large regiment of immunosuppressant therapy which causes many significant challenges for the patient. By bioengineering the heart out of the patient’s own cells we eliminate the need for that immunosuppressant therapy which could allow for a much better quality of life for the patient,” he continued.
With this platform technology in place, BIOLIFE4D is now well-positioned to build upon it and work towards the development of a full-scale human heart. This latest milestone also positions the company as one of the top contenders at the forefront of whole heart bioengineering, a field that is rapidly advancing.
However, beyond the scientific advancements the mini-heart represents, this is also an opportunity to provide the pharmacological industry and drug discovery companies a new tool for cardiotoxicity testing of new drugs and compounds. Until now the model used for predicting the cardiotoxicity effects of a new drug or compound was essentially limited to the animal model. But BIOLIFE4D intends to ultimately provide the mini-hearts as a more reliable model of predicting cardiotoxicity, claiming that there is no better predictor of how a human heart will react than a human heart. This also represents an opportunity to reduce the number of animals used for testing purposes, something which is already banned in quite a few regions, including India, the European Union, New Zealand, Israel, and Norway.
“We are already working closely with companies that provide cardiotoxicity testing services to the Pharma and drug discovery industries. All drugs, new compounds and anything else that currently undergoes cardiotoxicity testing requirements prior to entering the human market could be candidates for the mini-heart. After all, what would provide a better predictive model of how a human heart will respond than a human heart (albeit a scaled-down version)?” revealed Birla.
The mini-heart has many of the features of a human heart even though BIOLIFE4D has not been able to recreate the full functionality of a human heart yet.
“While we have bioengineered mini-hearts, and this in itself is a major accomplishment, a significant advancement in the field of whole heart engineering and moves us closer to bioprinting human hearts for transplantation, this accomplishment does not provide us with a specific time-line or a significant guidance on when the fully funcitional heart will be available.”
According to Birla, the most difficult part to 3D print a human heart at this point is the valves, due to the complex tri-leaflet geometry. But as they begin to scale up, they can anticipate that the complex vasculature that is needed to keep an organ viable could prove to be a big challenge.
Birla is convinced that “the algorithm used as a fundamental part of the mini-heart could change the way labs will bioprint organs in the future. We used very specific and highly customized printing parameters to bioprint the mini-heart which we have customized for our use in our lab and for our specific purposes. Some of the process ultimately could be leveraged for the bioengineering of other organs, but our overall process to bioengineer a human heart is unique to a heart.”
One of the huge advantages BIOLIFE4D enjoys is that they have been able to form strategic partnerships with various major research institutions and hospitals to provide them access to some of the most state-of-the-art facilities and equipment. Nevertheless, because of the highly confidential nature of their work, most of it is done in-house at the labs and by their own researchers.
The successful demonstration of a mini heart is the latest in a string of scientific milestones from BIOLIFE4D as it seeks to produce the world’s first 3D bioprinted human heart viable for transplant. Earlier in 2019, they successfully 3D bioprinted various individual heart components, including valves, ventricles, blood vessels, and in June of 2018 they 3D bioprinted human cardiac tissue (a cardiac patch).
The company states that their innovative 3D bioprinting process provides the ability to reprogram a patient’s own white blood cells to iPS cells, and then to differentiate those iPS cells into different types of cardiac cells needed to 3D bioprint individual cardia components and ultimately, a human heart viable for transplant.
This is crucial for a company that seeks to disrupt how heart disease and other cardiac impairments are treated, particularly by improving the transplant process so that in the future they can eliminate the need for donor organs. Heart disease is the number one cause of death of men and women in the United States each year. Heart diseases even claim more lives each year than all forms of cancer combined, yet countless individuals who need transplants are left waiting as there are not enough donors to meet demand and every 30 seconds, someone dies in the US of a heart disease-related event.
“While we have come a long way, and we are moving forward at a fast pace, we just don’t know how long it will take to achieve a full-scale heart. We have to keep in mind that mother nature had millions of years to perfect this process inside our bodies, while we just aren’t sure exactly how long it is going to take us to perfect the process outside of the body,” concluded Birla.
At BIOLIFE4D, they know there are still challenges on the way to the full-size human heart viable for transplantation, however, this achievement signals that they are on the right path. They highlighted that their success, as well as the significant advancements they have been able to achieve already, are a result of an incredible team effort, a multi-disciplinary group of researchers working on the project, from bioengineers to life scientists. Their team consists of people with specific skill sets and areas of expertise, all working hard to bring this incredible life-saving technology to the market in the shortest time possible.[Images: BIOLIFE4D]
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