Could bioengineering be a more powerful change agent in orthopedic and spine care than artificial intelligence (AI)? A raft of emerging bioengineering companies has filed significant patents and made other public announcements which promise to bring to market incredible ways of engineering tissues, creating proteins, even scaling up to complex organs.
In this article I’ll profile a major, well-funded initiative to apply these new technologies to regenerative medicine.
Redesigning Biology
In his book, “The Coming Wave: Technology, Power and the Twenty-First Century’s Greatest Dilemma” by DeepMind’s co-founder, Mustafa Suleyman writes; “Biology itself became an engineering tool. Alongside AI, this is the most important transformation of our lifetimes.”
“At the center of this wave sits the realization that DNA is information, biologically evolved encoding and storage system.” To a breathtaking degree, scientists can now alter DNA encoding and direct its course.
A (Very) Fast History of DNA Manipulation
Modern DNA manipulation first leaped over old fashioned mendelian genetics—cross breeding dogs, wheat, chickens or corn—in 1923 when Stanley N. Cohen figured out how to transplant genetic material from one organism to another. He successfully introduced frog DNA into bacterium. On the basis of that, Genentech was founded in 1976. In less than a year later, Genentech used engineered E. coli bacteria to produce the human hormone somatostatin.
The next leap forward came in 2003, when 92% of the human genome was successfully sequenced. “The code of life was now laid bare,” writes Suleyman.
Between 2003 and 2023, the cost of sequencing DNA collapsed from $1 billion to a few hundred dollars. The cost of sequencing DNA dropped a millionfold in less than 20 years. That’s a thousand times faster than Moore’s Law.
Editing DNA – Like any Oother Software Code
Clustered Regularly Interspaced Short Palindromic Repeats—also known as CRISPR—edits DNA using Cas9, an enzyme that acts like a pair of scissors. CRISPR cuts DNA strands precisely and can edit and modify any DNA whether its bacterium or large mammals (like us). Specifically, editing germ-line cells that form eggs or sperm—ensuring that these changes become generational.
Using DNA editing technologies, we now have vaccines that don’t trigger immune responses. RNA editing has exploded on the scene with new treatments for high cholesterol (Ozempic), cancer and inflammatory disease—which, it should be noted, are piling up behind the clinical trial bottleneck.
“Like AI, genetic engineering is a field in blistering motion, evolving and developing by the week, a massive global concentration of talent and energy beginning to bear real fruit,” writes Suleyman. “CRISPR use cases are multiplying from tomatoes rich ultrarich in vitamin D to treatments for conditions including sickle-cell disease and beta-thalassemia (a blood disorder producing abnormal hemoglobin).”
Biotech used to be expensive. CRISPR and the genetic sequencing revolution is democratizing biological science in truly profound ways. What used to take 20 years, grad students tackle in weeks. Companies now sell genetic engineering kits for less than $2,000 which include live frogs, crickets, a mini-centrifuge, a polymerase chain reaction machine and all the reagents and materials you need.
A desktop DNA synthesizer is only $25,000.
Here’s the kicker. CRISPR is just the beginning. London’s DNA Foundry at the Imperial College of London can create and test 15,000 different genetic designs in a single morning.
We are now in the age of reading, writing, and editing the code of tissue repair, disease and, of course, life itself.
A Human Tissue Foundry
Recently, the Department of Defense (DoD) announced that it would fund an 87-member coalition to develop next-generation cell, tissue, and organ “manufacturing” for wounded service members.
The new organization is led by the nonprofit Advanced Regenerative Manufacturing Institute (ARMI)—founded in 2017 and based in Manchester, New Hampshire.
The funds are coming from the Army Contracting Command and amount to $80 million in DoD funds and more than $214 million in non-federal cost sharing. The funding is supposed to last at least seven years.
This “next generation” initiative exists under the auspices of the Advanced Tissue Biofabrication team—which was organized by ARMI and led by ARMI’s founder, Dean Kamen. ARMI, a non-profit company, pulls together 47 companies, 26 academic institutions, and 14 government and nonprofit organizations, to create, in effect, a human tissue foundry.
The foundry’s goal is to advance and scale fabrication of complex biological systems from raw materials, including living cells, DNA (we expect) and 3D printed matrices/scaffolds to form functional cells, tissues and organs—and employing the most advanced engineering and AI systems available.
Frank Kendall, former secretary of the Air Force and Undersecretary of Defense for Acquisition, Technology and Logistics, explained in a Department of Defense article the “why” of this biofabrication initiative.
“The ‘why’ for this institute is one that is extremely important to all of us and personal to many of us in the Defense Department—restoring form, function and appearance for our wounded warfighters and changing what is possible for the many Americans who’ve spent far too long on the organ-transplant waiting list,” said Kendall.
The foundry is chocked full of state-of-the-art tissue manufacturing, cell and biomaterial processing, 3-D bioprinting, automation and nondestructive testing technologies. The simple goal is to standardize tissue production—perhaps even at the hospital level.
Its other goal is to scale up. Meaning, drive down pricing and increase supply to the extent that surgeons and other physicians will increasingly employ cell therapies, engineered replacement tissue and biopharmaceutical products in their practices.
Dean Kamen described the essential function of this wide-ranging biologics foundry saying: “We can supply essentially what the printing press did to get all these ideas to the world that needs them. We need to essentially make the printing press for the world of regenerative medicine.”
A few weeks ago, one of the companies founded by ARMI, BioFabUSA sent OTW a press release. In it, the company said: “BioFabUSA is removing the hurdles in manufacturing cells, tissues and organs.” Furthermore, the company predicts that it will be able to “reliably produce and scale regenerative therapies.”
Since its founding in 2017, BioFabUSA has closed and automated multiple manual, time-intensive tissue engineering processes including Epibone’s autologous bone tissue manufacturing process, which uses isolated and expanded patient-derived mesenchymal stem cells (MSCs) and decellularized bovine bone to provide anatomically tailored bone reconstruction for patients with trauma, bone-related genetic defects or reconstruction after the treatment of cancer and other illnesses.
One ARMI member company Ann Arbor, Michigan-based STEL Technologies LLC develops bioengineered anterior cruciate ligaments (ACLs). STEL (Skeletal Tissue Engineering Laboratory) Technologies was founded by researchers at the University of Michigan.
ARMI is helping STEL scaling out and mass-producing tissue-engineered ACLs and more. According to STEK co-founder and CEO Lisa Larkin, “My tissue-engineered ACL product and the bioreactor designed to fabricate the product were the first two technologies selected by ARMI and BioFabUSA to develop a Tissue Foundry around.”
Stay tuned. Bioengineering—which is increasingly looking like software engineering—could, along with artificial intelligence tools, transform and disrupt the kinds of implants used to treat musculoskeletal disease and trauma.
