NBIL’s formulation is a trade secret, but bioinks generally combine tissue cells with growth materials and structural gels. A research team from Yale and Rensselaer Polytechnic Institute in the US, who recently published a paper in the journal, Tissue Engineering, used a mix of infant foreskin, umbilical cord blood, placenta tissue and collagen from rat tails. The younger the tissue, better for culturing.
The NBIL team had struggled to finetune their bioink and process, with so many variables at play in this frontier field. One failure followed another. “Sometimes we would see the skin forming, but it would be too fragmented by the end," recalls Piyush Padmanabhan, co-founder of NBIL. “One day we made a small change in the medium for our cell culture. And we got human skin."
This was a couple of months ago and a huge moment for this biotech startup founded in Bengaluru in 2016. A scientist first saw the well-formed skin in a tray. A closer look under a huge microscope confirmed the breakthrough. He called Padmanabhan and his co-founder Pooja Venkatesh to the lab. Two other co-founders, Alok Medikepura Anil and Ratandeep Singh Bansal, were out of town.
“Have you ever peeled the dried skin of your lip? It was that thin and about 1.5cm in diameter," says Padmanabhan, a biotech graduate from Vellore Institute of Technology who worked for Biocon and Roche before plunging into the startup world.
There are many hurdles to cross on the road to commercialization of NBIL’s human skin whose proprietary name is Innoskin. But the newfound knowhow opens up several possibilities.
3D bioprinted skin has both medical and cosmetic applications. Victims of burns and other wounds could get relief from its commercial availability, once it is developed further to be good enough for grafting. A missing link is the vasculature that will allow lab skin to integrate with the human body’s blood vessels.
More immediate uses are in the pharmaceutical and cosmetics industries for testing before their release in the market. A societal and regulatory pushback against use of animal skin for testing cosmetics and drugs is making lab skin attractive to make-up and pharma companies.
A number of companies and research labs around the world are working on producing human skin in a commercially viable manner. But NBIL has the advantage of being one of the first with skin in the game. It has filed for patents related to its 3D bioprinting process, while its novel bioink’s composition remains a closely guarded secret internally.
Petri Dish to Printers
The creation of human skin in the lab for commercial use dates back to 1993 when MatTek, a company founded by two chemical engineering professors at MIT, launched Epiderm. They took live tissue cells from cosmetic surgeries and circumcisions, then cultured them in petri dishes to produce skin. MatTek continues to produce lab skin at two facilities in Massachusetts and Slovenia.
More recently, L’Oreal came up with an alternative called Episkin, which it sells to other companies to test the safety and efficacy of new ingredients and products.
Both Epiderm and Episkin are too expensive and inconsistent for widespread use, compared to producing human skin with a newer, automated process like 3D bioprinting.
L’Oreal has tried to adopt 3D bioprinting by partnering with a San Diego startup Organovo that makes 3D human tissue. But Organovo burnt its fingers in an artificial liver tissue programme which it was forced to suspend in August this year. Organovo’s stock is trading at 50 cents compared to its $12.50 price in 2013 after the startup’s Nasdaq listing.
NBIL has been careful not to bite off more than it can chew. It has taken the path of least resistance by focusing on skin, and that too for cosmetic rather than clinical use. However, it is simultaneously building the capability to enter other domains with various products as the market matures.
“Everyone in this field is looking at the holy grail which is 3D bioprinted tissues and organs that can save lives. But that’s further down the line, dependent on regulatory clearances and getting the technology right," says Alok Medikepura Anil. “So we want to start servicing the cosmetics, FMCG and pharma sectors, understand how close our product is to actually mimicking the human biology of skin, get that back into our lab, and subsequently create a clinical pipeline."
At the outset, NBIL built its own 3D bioprinter instead of buying one of those available in the market. This not only cuts costs but also allows the team to customise the printer for specific use cases. “We did not want to be dependent on someone else’s engineering ecosystem. So we decided early on that to be truly a 3D bioprinting company, we needed to do both the engineering and biotech," says Padmanabhan.
Bioprinting involves working with a variety of biomaterials. The challenge lies in ensuring that live cells are not harmed as bioink is extruded from the printer layer by layer. “There’s constant communication between the engineering and biotech teams," says Pooja Venkatesh. “The biotech team may tell the engineers what temperature to maintain around the bioink. Or the engineers could notice a variation in the pressure and tell the biotech team there could be something wrong with the viscosity of the bioink."
NBIL has not only been using its 3D bioprinter internally but also making it available to other research and commercial organizations that want to take advantage of its flexibility for customization.
This created a revenue source for the startup which has allowed it to go through its development stage with angel funding and government grants rather than diluting equity too early with venture capital.
This year, a major validation of its product came from pharma giant Merck when it picked NBIL for the accelerator programme at its innovation centre in Darmstadt, Germany. “Our technology is being used for testing applications of 3D bioprinting at Merck," says Padmanabhan, who just returned from Germany.
The association with Merck gives NBIL a front row seat into emerging use cases for 3D bioprinting in medicine. Adoption is easier in the cosmetics industry for now, but the real deal will be 3D bioprinted skin grafts, organ tissue, and other novel products like 3D printed meat which are round the corner.
Malavika Velayanikal is a contributing editor with Mint. Write to her at email@example.com