BIOLIFE4D Successfully 3D Bioprints a Miniature Human Heart—One Step Closer to Bioprinting Transplantable Organs

3D printer

Bioprinting is a type of 3D printing to manufacture biological. So far, the process has been used to develop organs or organoids—smaller versions of organs that are at least partially functional—and can be used as models for research. Ultimately researchers hope they can bioprint organs that can be used for transplants.

Chicago-based BIOLIFE4D recently bioprinted a 3D miniature human heart, which they say is a big step toward producing a full-sized human heart that could be used for transplant. The company has research facilities at JLABS in Houston.

The miniature heart had all the structures of a full-sized heart, with four internal chambers. The company says it is as close as anyone has gotten to a fully functioning heart via 3D bioprinting.

“We are extremely proud of what we have accomplished, from the ability to 3D bioprint human cardiac tissue last summer to a mini heart with full structure now,” said Ravi Birla, the company’s chief science officer. “These milestones are a testament to the hard work of our team and the proprietary process we have developed that enables this type of scientific achievement. We believe we are at the forefront of whole heart bioengineering, a field that has matured quickly over the last year, and well positioned to continue our rapid scientific advancement. Today is an exciting day, but we continue forward earnestly toward the end goal of 3D bioprinting whole human hearts.”

3D printing is sometimes called “additive manufacturing.” It is a way of making three-dimensional solid objects from a digital file. In many ways, the only limitations are the limits on the complexity of the design. 3D printing used in industrial applications typically use carbon fiber as a source material. But bioprinting uses a variety of biological materials, such as single cell suspensions, as the source materials.

In the case of BIOLIFE4D’s heart, they developed a proprietary bioink with a unique composition of different extracellular matrix compounds. These compounds are very similar to the properties of a mammalian heart. The company also developed a novel bioprinting algorithm made up of printing parameters optimized for the whole heart, which it coupled with patient-derived cardiomyocytes. Although the heart is small in size, it has many of the features of a human heart.

BIOLIFE4D isn’t the only company working in this specific area. In April, researchers at Tel Aviv University successfully printed the first 3D human heart. The research team used the patient’s own cells and various biological materials such as collagen and glycoprotein. Their work was published in the journal Advanced Science.

“This heart is made from human cells and patient-specific biological materials,” stated Tal Dvir, lead researcher. “In our process these materials serve as the bioinks, substances made of sugars and proteins that can be used for 3D printing of complex tissue models. People have managed to 3D-print the structure of a heart in the past, but not with cells or with blood vessels. Our results demonstrate the potential of our approach for engineering personalized tissue and organ replacement in the future.”

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Dvir and his team began by taking biopsies of fatty tissues from the omentum, a fold of visceral peritoneum that hangs from the stomach, in the abdomen of humans and pigs. They then separated the cellular materials from extraneous materials and reprogrammed the cellular materials to become pluripotent stem cells. From these, they were able to develop all three body layers that had the potential to produce any cell or tissue in the body.

They then built an extracellular matrix from collagen and glycoproteins into a hydrogel using the bioprinter. They mixed the cells with the hydrogel, which were then differentiated into cardiac or endothelial cells. This created what they’re calling “patient-specific, immune-compatible cardiac patches complete with blood vessels.”

From that point, they then created an entire—but small—bioengineered and bioprinted human heart.

Last year, Poietis, a Pessac, France-based company, along with Prometheus, a division of Skeletal Tissue Engineering at Leuven, Belgium, announced they had entered into a two-year Collaborative Research Agreement to develop high-precision 3D Bioprinting of tissue engineered Advanced Therapeutic Medicinal Products (ATMPs) for skeletal regeneration.

Prometheus focuses on tissue-engineered ATMPs with a focus on skeletal regeneration. Poietis is interested in using 3D bioprinting of single cell suspensions into large, patterned tissue structures, especially “the laser-assisted bioprinting of multicellular micro-aggregates embedded in bioinks for the formation of layered cellular structures.”

What this comes down to is a collaboration to “print” bone that can be used in transplants or other orthopedic, musculoskeletal or spine-related applications.

Poietis already has a product on the market, Poieskin, a human full thickness skin model produced entirely by 3D bioprinting. It is made up of a “dermal compartment composed of primary human fibroblasts embedded in a collagen I matrix overlaid by a stratified epidermis derived from primary human keratinocytes.”

In May, researchers with Rice University developed a new approach resulting in “exquisitely entangled vascular networks that mimic the body’s natural passageways for blood, air, lymph and other vital fluids.” The research was published in the journal Science.

“One of the biggest roadblocks to generating functional tissue replacements has been our inability to print the complex vasculature that can supply nutrients to densely populated tissues,” stated Jordan Miller of Rice University. “Further, our organs actually contain independent vascular networks—like the airways and blood vessels of the lung or the bile ducts and blood vessels in the liver. These interpenetrating networks are physically and biochemically entangled, and the architecture itself is intimately related to tissue function. Ours is the first bioprinting technology that addresses the challenge of multivascularization in a direct and comprehensive way.”

Also in May, San Diego-based Organovo entered a collaboration agreement with Melissa Little at the Murdoch Children’s Research Institute (MCRI), The Royal Children’s Hospital, in Melbourne, Australia, and Ton Rabelink at Universiteit Leiden (LUMC), Leiden, Netherlands. The collaboration will focus on expanding the use of 3D bioprinted stem cell-based therapeutic tissues. The goal is to develop treatments for end-stage renal disease.

The collaboration will utilize Organovo’s bioprinting platform, MCRI’s advanced stem cell differentiation technology, and LUMC’s cell lines and clinical expertise. The partnership is funded by Stem Cells Australia and CSL Limited.

And in 2018, United Therapeutics and Lung Biotechnology made a collaboration pact with Israeli 3D bioprinting company CollPlant. United paid CollPlant $5 million up front with up to $15 million in milestones to supply bioink to Lung Biotechnology. CollPlant’s recombinant human collagen (rhCollagen) is grown from tobacco plants engineered with five human genes. The purified collagen can be used as a scaffold for 3D bioprinting solid organs.

BIOLIFE4D has had several breakthroughs in this area. Earlier this year it successfully 3D bioprinted individual heart components, and in June 2018 it successfully 3D bioprinted a cardiac patch out of human cardiac tissue.

The company’s 3D bioprinting process gives the researchers the opportunity to reprogram a patient’s own white blood cells to induced pluripotent stem (iPS) cells, then to force the iPS cells to differentiate into different types of cardiac cells to be used as individual cardiac components and eventually, into a human heart that could be used for transplant.

“This is an incredibly exciting time for BIOLIFE4D, and we are so proud of Dr. Birla and the team for this tremendous accomplishment,” said Steven Morris, the company’s chief executive officer. “We began this journey with an end goal of developing a technology that has the potential to save lives, and we are a step closer to that today. We will continue our work until we are able to 3D bioprint full-sized hearts for viable transplant, and change the way heart disease is treated forever.”

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