Implantable 3D-printed organs could be coming sooner than you think

At MBC Biolabs, an incubator for biotech startups in San Francisco’s Dogpatch neighborhood, a team of scientists and interns working for the small startup Prellis Biologics have just taken a big step on the path toward developing viable 3D-printed organs for humans.

The company, which was founded in 2016 by research scientists Melanie Matheu and Noelle Mullin, staked its future (and a small $3 million investment) on a new technology to manufacture capillaries, the one-cell-thick blood vessels that are the pathways which oxygen and nutrients move through to nourish tissues in the body.

Without functioning capillary structures, it is impossible to make organs, according to Matheu. They’re the most vital piece of the puzzle in the quest to print viable hearts, livers, kidneys and lungs, she said.

“Microvasculature is the fundamental architectural unit that supports advanced multicellular life and it therefore represents a crucial target for bottom-up human tissue engineering and regenerative medicine,” said Jordan Miller, an assistant professor of bioengineering at Rice University and an expert in 3D-printed implantable biomaterial structures, in a statement.

This real-time video shows tiny fluorescent particles – 5 microns in diameter (the same size as a red blood cell) – moving through an array of 105 capillaries printed in parallel, inside a 700 micron diameter tube. Each capillary is 250 microns long.

Now, Prellis has published findings indicating that it can manufacture those capillaries at a size and speed that would deliver 3D-printed organs to the market within the next five years. 

Prellis uses holographic printing technology that creates three-dimensional layers deposited by a light-induced chemical reaction that happens in five milliseconds.

This feature, according to the company, is critical for building tissues like kidneys or lungs. Prellis achieves this by combining a light-sensitive photo-initiator with traditional bioinks that allows the cellular material to undergo a reaction when blasted with infrared light, which catalyzes the polymerization of the bioink.

Prellis didn’t invent holographic printing technology. Several researchers are looking to apply this new approach to 3D printing across a number of industries, but the company is applying the technology to biofabrication in a way that seems promising.

The speed is important because it means that cell death doesn’t occur and the tissue being printed remains viable, while the ability to print within structures means that Prellis’ technology can generate the internal scaffolding to support and sustain the organic material that surrounds it, according to the company.

The video above, courtesy of Prellis Biologics, shows real-time printing of a cell encapsulation device that is useful for producing small human cells containing organoids. The structure is designed to be permeable and the size is 200 microns in diameter and can contain up to 2000 cells.

Prellis isn’t the first company to develop three-dimensional organ printing. There have been decades of research into the technology, and companies like BioBots (which made its debut on the TechCrunch stage) are already driving down the cost of printing living tissue.

Now called Allevi, the company formerly known as BioBots has seen its founders part ways and its business  strategy shift (it’s now focusing on developing software to make its bioprinters easier to use), according to a report in Inc. Allevi has slashed the cost of bioprinting with devices that sell for less than $10,000, but Prellis contends that the limitations of extrusion printing mean that technology is too low resolution and too slow to create capillaries and keep cells alive.

Prellis’ organs will also need to be placed in a bioreactor to sustain them before they’re transplanted into an animal, but the difference is that the company aims to produce complete organs rather than sample tissue or a small cell sample, according to a statement. The bioreactors can simulate the biomechanical pressures that ensure an organ functions properly, Matheu said.

“Vasculature is a key feature of complex tissues and is essential for engineering tissue with therapeutic value,” said Todd Huffman, the chief executive officer of 3Scan, an advanced digital tissue imaging and data analysis company (and a Prellis advisor). “Prellis’ advancement represents a key milestone in the quest to engineer organs.”

Matheu estimates that it will take two-and-a-half years and $15 million to bring implantable organs through their first animal trials. “That will get a test kidney into an animal,” she said.

The goal is to print a quarter-sized kidney that could be transplanted into rats. “We want something that would be able to handle a kidney that we would transplant into a human,” Matheu said.

One frame of a 3D map of animal tissue from 3Scan .

Earlier this year, researchers at the University of Manchester href=”https://newatlas.com/working-kidney-cells-grown-mice/53354/”> grew functional human kidney tissue from stem cells for the first time. The scientists implanted small clusters of capillaries that filter waste products from the blood that had been grown in a Petri dish into genetically engineered mice. After 12 weeks, the capillaries had grown nephrons — the elements that make up a functional human kidney.

Ultimately, the vision is to export cells from patients by taking a skin graft or blood, stem cell or bone marrow harvest — and then use those samples to create the cellular material that will grow organs. “Tissue rejection was the first thing I was thinking about in how I was designing the process and how we could do it,” says Matheu.

While Prellis is spending its time working to perfect a technique for printing kidneys, the company is looking for partners to take its manufacturing technology and work on processes to develop other organs.

“We’ll be doing collaborative work with other groups,” Matheu said. “Our technology will come to market in many other ways prior to the full kidney.”

Last year, the company outlined a go-to-market strategy that included developing lab-grown tissues to produce antibodies for therapeutics and drug development. The company’s first targeted human tissue printed for clinical development were cells called “islets of Langerhans,” which are the units within a pancreas that produce insulin.

“Type 1 diabetics lose insulin-producing islets of Langerhans at a young age. If we can replace these, we can offer diabetes patients a life free of daily insulin shots and glucose monitoring,” said Matheu in a statement at the time.

Matheu sees the technology she and her co-founder developed as much about a fundamental shift in manufacturing biomaterials as a novel process to print kidneys, specifically.

“Imagine if you want to build a tumor for testing… In the lab it would take you five hours to print one… With our system it would take you three and a half seconds,” said Matheu. “That is our baseline optical system… The speed is such a shift in how you can build cells and fundamental structures we are going to be working to license this out.”

Meanwhile, the need for some solution to the shortage in organ donations keeps growing. Matheu said that one in seven adults in the U.S. have some sort of kidney ailment, and she estimates that 90 million people will need a kidney at some point in their lives.

Roughly 330 people die every day from organ failure, and if there were a fast way to manufacture those organs, there’s no reason for those fatalities, says Matheu. Prellis estimates that because of the need for human tissue and organ replacement alternatives, as well as human tissue for drug discovery and toxicology testing, the global tissue engineering market will reach $94 billion by 2024, up from $23 billion in 2015.

“We need to help people faster,” says Matheu. 

Southern California needs to find its hub for it to develop its own tech ecosystem

Recognizing the tens of billions of dollars that the Southern Californian region leaves on the table, because it hasn’t taken its rightful place in the American technology industry, a new group called  the Alliance for Southern California Innovation has just released a report to analyze how SoCal can work to assume its pole position.

Through interviews with 100 leaders of the technology ecosystem and an analysis of venture capital funding for the region, the organization has concluded (with the help of the Boston Consulting Group) that the promise of a regional rival to Northern California’s silicon valley won’t be fulfilled without the establishment of a geographic hub and a willingness to overcome regional differences.

Founded by Steve Poizner last year to accelerate the growth of a startup entrepreneurial ecosystem in Southern California, The Alliance is building a network of investors, entrepreneurs and universities to provide ballast in the south to the dominance of the Northern California tech industry.

The Alliance estimates that Southern California’s tech community could be one-third the size of Silicon Valley’s by supporting or further developing the six pillars it already has for innovation to occur.

The potential impact making these changes could have is an added 200,000 new jobs and growth of $100 billion for the whole economic region.

“Over the past several years we have observed a significant decrease in startups leaving SoCal,” said Greg Becker, CEO of Silicon Valley Bank . “We’ve also seen a substantial inflow of venture capital from all over the world.”

In fact, as is well-reported, the luster of Silicon Valley is fading. As BCG writes in its report:

The good news for SoCal and any region with tech ambitions is that the Bay Area has in some ways been too successful. Our research revealed a saturation level causing unprecedented challenges, starting with exorbitant housing prices and runaway operating costs that accelerate a startup’s “burn rate”—its monthly spending.

Los Angeles investor Mark Suster, a general partner with Upfront Ventures, has been beating the drum for Los Angeles as a new tech hub for a while — and billion dollar exits for Ring and Dollar Shave Club, in addition to the public offering for Snap, lend credence to his position.

Suster has also noted for years that the region produces more technology doctorates than any other geography in the United States. Caltech generates more patents than any other university while UCLA boasts more startups founded by its graduate than any other school in the nation. Meanwhile, UCSD in San Diego has a deep bench of biotechnology expertise stemming from its proximity to the Sanford Consortium for Regenerative Medicine, the Salk Institute, and the Scripps Research Institute.

However, to thrive, BCG recommends taking six steps to bolster the the ecosystem and its chances to begin to catch up to Silicon Valley.

The consulting firm says that Southern California needs more local venture capital; the individual geographies need to work to promote their regional strengths; regions need to collaborate more closely with each other; founders need to start gunning for that IPO slot instead of taking acquisition offers; the region’s commitment to diversity needs to be emphasized; and finally the embarrassment of entrepreneurial riches needs to be promoted abroad.

“Southern California is a region of extreme innovation; however, it is so spread-out, making it hard to navigate,” said Steve Poizner founder and board chair of the Alliance, in a statement. “We believe by finding, filtering and aggregating exciting startups from top universities, research institutes, and incubators/accelerators, we can demonstrate the combined strength of SoCal in a compelling way to top investors and thought leaders.”