stripped the donor trachea of all of its cells first, leaving just a collagen tube. They then used the tube as a scaffold upon which to build the new organ, placing it in the bioreactor and seeding it with cells derived from the patient’s own bone marrow and airway. After incubating the trachea in the bioreactor for four days, Macchiarini implanted it into Castillo.
Green was floored by the paper. He e-mailed Macchiarini and wound up licensing the bioreactor technology from two of his colleagues, Sara Mantero and Adelaide Asnaghi, engineers at the University of Milan who invented the technology. Harvard Bio brought the device in-house, looking for ways to refine it for commercial use.
“At that point, we looked at ourselves as a bioreactor company,” Green says.
Harvard Bio, however, quickly made a few key realizations. Green says, that it didn’t make any sense to sell bioreactors on their own without also providing scaffolds for the organs that doctors would want to grow in them. Though Macchiarini’s team had succeeded in using a cadaver organ as a scaffold for Castillo’s new trachea, using a synthetic scaffold made out of rubbery nanomaterials would eliminate the need to find a donor organ.
Such scaffolds were occasionally being made in academic labs, but those lacked the quality control procedures necessary for making commercial medical products, Green says. Harvard Bio also collaborated for a time with an Ohio-based startup called Nanofiber Solutions, which constructed scaffolds out of polymers like PET. Harvard Bio used Nanofiber’s scaffolds to create tracheas for four patients, but Green says that three of them have since had to be replaced because they were essentially collapsing inward. (Nanofiber, for its part, disputes this part of the story. The two companies have clashed over intellectual property in the past, according to the Columbus Business First.)
Ultimately Harvard Bio decided it would have to manufacture the scaffolds itself. And in early conversations with the FDA it became clear that in order to win regulatory approval the company would also have to control the process of seeding patient’s cells into the scaffolds to create the engineered organs, Green says. If the company simply supplied the scaffolds and bioreactors to doctors and left the seeding process up to them the risk of contamination would be too high and quality control would be lacking, he says.
So Harvard Bio set aside the idea of selling tools for making tracheas and began focusing on a plan for supplying the organs themselves. The idea is that a surgeon would select the scaffold that best fit a particular patient from a menu of size options and send the company some of the patient’s cells. Harvard Bio would take care of the seeding and incubation steps and, within a few days, ship a completed organ back to the surgeon, who would perform the implantation.
The growing project shifted Harvard Bio’s center of gravity. While the company kept selling its lab instruments, it was also investing heavily in what was fast becoming a full-scale organ engineering business. The project was an outlier, and a burden on Harvard Bio’s cash resources.
“I really believed it was necessary to split the companies up,” Green says.
So on Dec. 1, 2012, HART, filed an S-1 with the Securities and Exchange Commission. The plan was originally for Harvard Bio to give HART a $10 million investment and offer public investors 20 percent of the spin-off through an IPO (Harvard Bio would sell the rest later). Instead, in October, the companies decided to make it a clean break. Harvard Bio instead gave its shareholders one HART share for every four Harvard Bio shares that they already owned, kicked in $15 million, and essentially washed its hands of the regenerative medicine project.
In the process, a few of Harvard Bio’s key leaders fled to HART. Thomas McNaughton, Harvard Bio’s CFO, took up the same role at HART, and onetime Harvard Bio CEO Graziano joined HART’s board as a director.
With the team in place, now it’s on to the hard part—moving beyond a few last-resort surgeries, to establishing engineered organs as real options for patients.
To date, HART’s bioreactors have been used to prepare tracheas for just
