It turns out the secrets of science aren’t always on the tip of your nose.
At Organogenesis, a Canton-based tissue regeneration firm, the company’s signature product, Apligraf, is derived from the cells of foreskins donated by the mothers of newborn baby boys. A single donor can eventually generate up to two football fields’ worth of Apligraf, according to Dario Eklund, the company’s VP of bioengineering and bioaesthetics.
That’s because the newborn donors’ cells are “so young, so robust, so full of life, that they can divide and build cell banks,” Eklund explains.
Apligraf, a circular patch with skin-like dermal and epidermal layers, about the diameter of a hockey puck and just a quarter of a millimeter thick, is manufactured in Canton using epidermal fibroblasts and dermal keratinocytes from the donated samples, which are seeded into a collagen solution. As they develop, they mimic the growth of actual human skin — minus hair follicles, blood vessels and, mercifully, sweat glands — stimulating the production of protein and growth factors that spur the patient’s own cells into action to heal damaged tissue.
“If you took a skin graft and covered the wound, it would become part of the patient,” Eklund notes. Instead, Apligraf is absorbed into the body, so completely that eight weeks after application female patients show no sign of male XY chromosomes.
“It doesn’t persist,” Eklund says. “It goes in there, it jump-starts the human [healing] process, it does its job and it just goes away.”
Tissue regeneration has made tremendous strides in the last two decades, with a growing number of companies like Organogenesis throwing their hats into the ring. Founded in 1985 by the late M.I.T. scientist Eugene Bell, Organogenesis already has one bankruptcy recovery under its belt and still operates on razor-thin margins. But with an ambitious expansion plan under way and several new products in the development pipeline, the company is once again poised for growth.
And the time may be right. The worldwide tissue engineering and regenerative medicine market could grow 16 percent annually through 2013, according to a report by market research firm Life Science Intelligence, to more than $118 billion.
Room for growth
{IMAGELEFT:http://www.massdevice.com/sites/default/wp-content/uploads/headshots/Eklund_Dario_100x100.jpg}Massachusetts almost lost the bragging rights to the first living, cell-based tissue regeneration product. The Bay State’s infamously high cost of doing business had Organogenesis preparing to leave it behind, Eklund tells MassDevice in his Canton office.
“We didn’t want to [move],” he explains, “but for cost reasons it just made no sense to stay anymore.”
That was before the company landed a $7.4 million grant from the Massachusetts Life Sciences Center, a quasi-public agency charged with fostering growth in the Commonwealth’s pharmaceutical, biotech and medical device industries.
Now, instead of pulling up stakes in Massachusetts, Organogenesis is building what will be the largest cell therapy manufacturing site on the planet.
Outside Eklund’s window, trailers line the campus, with some 200 on-site employees squeezed into temporary quarters as the existing plant is expanded from 80,000 square feet to 250,000, which will add 280 new jobs.
The life sciences grant will help fund the expansion, propelling the company into its next phase of product development using a newly automated manufacturing process.
The buildout is needed for the company’s next generation of products. In addition to Apligraf, which accounts for 95 percent of all sales, Organogenesis is developing three other regenerative tissue treatments.
Like Apligraf, VCT01 is a two-ply, skin-like product, but its matrix is formed solely using fibroblasts, with keratinocytes seeded on top to form an epidermal layer. It’s in the late-stage development phase.
Then there’s a 3D collagen matrix manufacturing process, still in the R&D stage, which uses the electro-spinning technology Organogenesis acquired in its February 2008 buyout of Baton Rouge, La.-based NanoMatrix. Viewed under a microscope, the electro-spun nanostructures closely resemble the structure of collagen in human skin.
“In a way, it was a defensive move to buy [NanoMatrix],” Eklund says. “We thought it was an interesting platform that could have a lot of uses in our space, and we certainly didn’t want it to go into the hands of a competitor.”
Finally, there’s FortaFlex, a bio-engineered collagen substitute used in surgical procedures in place of synthetic materials, skin grafts or cadaver grafts to reinforce weak tissue, repair tendons and dress wounds.
FortaFlex is also used in a device being developed in collaboration with Boston-based NMT Medical Inc., the BioStar treatment for patent foramen ovale — an opening between the left and right upper cardiac chambers. In patients with PFO, that opening fails to fully close after birth, allowing blood to bypass the lungs and return, unoxygenated, to the body.
The traditional treatment involves covering the opening with a synthetic Dacron patch. The BioStar device uses a surgical wire scaffold sandwiched between sheets of FortaFlex, which is folded and slipped into the atrial opening. It unfolds, sealing the hole, and the patient’s tissue grows around the implant and absorbs up to 95 percent of it. Only the wire scaffold is left.
{IMAGELEFT:http://www.massdevice.com/sites/default/wp-content/uploads/headshots/Davis_Richard_100x100.jpg}And while that’s an improvement over the prototype versions of the device, the scaffold can present problems during later heart surgeries, making for difficult maneuvering if surgeons need to pass through it. The two firms are in pre-clinical trials for a fully absorbable solution called BioTrek.
“The original design was impossible to pass through, NMT COO Richard Davis says. “BioStar is difficult to cross through. BioTrek will have nothing to cross through.”
Back from bankruptcy
Organogenesis is on the upswing following the painful bankruptcy in 2002 that forced it to lay off 100 workers. Founded in 1985 as a spin-off to develop ideas born at M.I.T., the company sold the marketing rights to Apligraf, its then-only product, to Swiss pharma giant Novartis in 1996 in order to focus on its manufacturing operation.
Six years later Organogenesis re-acquired the marketing rights, but was soon forced to file for Chapter 11 bankruptcy protection. Many of the laid-off workers are now back with the company after a rescue by private investors.
Since its initial approval for treating chronic venous leg ulcers by the U.S. Food and Drug Administration in 1998, more than 250,000 Apligraf units have shipped — every one grown from just 11 donors.
It’s those fecund donor cells that make the Organogenesis business model feasible, Eklund says, because of the great cost of screening each donation.
“The FDA makes us test this donor tissue for more or less every disease known to man,” he notes, a process that costs about $250,000 per tissue line. “If we had to do this for 1,000 units, we just couldn’t do this.”
Apligraf costs about $1,400 per application, which is covered by Medicare, Medicaid and about 350 private insurers.
The future
Though the tissue regeneration products Organogenesis develops and manufactures in Canton could be applied to a variety of treatments, Eklund says the company plans to keep its eye on its sweet spot — collagen and skin cell therapies.
“That’s what we really are world leaders in,” he says.
Organogenesis expects to submit a soft-tissue regeneration oral surgery product for FDA approval this year, which uses living cells to stimulate growth. There’s more to come — more products, more collaboration and, the firm hopes, more sales — but all within the scope of its core focus.
“Our company has the ability to [work with] all kinds of body parts,” Eklund explains. “We could get into nerves, we could get into brain cells, we could get into bone and cartilage. But we have to ask ourselves, ‘What are we really the best in the world at? What is sustainable? What can we continue to be the best in the world at?’”
The answer, he says, is tissue regeneration.
“It’s a new industry. We’re a big fish in a small pond right now. The biggest in the field. But the fish is growing and the pond is growing.”
Click here to learn about another Organogenesis product, Revitix, and its, well, odiferous origins.
