Full disclosure: I did not receive any financial compensation (I even refused lunch) for the writing and coverage. Yeshi Etar invited me to them to get an impression of the company, and this is the result.
"You have to see my thighs." I was contacted by Yishai Ether, an experienced biomedical entrepreneur and founder of BioChange.
"No, I don't." I responded immediately, as if I receive such orders every day.
"Indeed yes." he insisted. "I injected myself with our new implant, and you should see how it develops. This has a revolutionary meaning for the entire world of medicine."
So I agreed. I have a weakness for scientists and entrepreneurs who believe in their ideas enough to try them on themselves. Marshall Barry, for example, drank an entire petri dish full of bacteria, to try to prove that they cause an ulcer - an inflammation of the stomach wall. He did suffer from an ulcer, and the entire scientific community collectively suffered from it. After that he won the Nobel Prize for the discovery.
To be fair, not all confident scientists and inventors are equally successful. When Franz Reichelt climbed the Eiffel Tower and prepared to jump from it with a makeshift parachute suit he had invented himself, he was absolutely convinced that he would make it to the ground safe and sound. He leaped from the tower with a smile, fell like a stone when the suit refused to open, and where he hit the ground was left with a crater 15 centimeters deep. He did not survive the fall.
But at least they wrote about him in the newspaper.
Either way, self-experiments - and self-experiments - always attract attention. All the more so when they are backed by serious research. And it seems that Ether really hung himself up high and did many, many experiments before agreeing to risk the safety of his hips - and more on that later.
But what is he even trying to do?
Vision of BioChange
"Our vision is to restore to the body the ability to do what it knew best at the beginning of life - to grow and renew itself. When our product is introduced into the body, it encourages the regeneration (regrowth) of tissues within the adult body." Ether explained to me when I met him. "And later, not only tissues but also whole organs."
The site has a history of successful entrepreneurship in the field of biomedicine. He has already founded four start-ups, of which BioChange is the latest. Before that, he founded LifeBond, which focused on developing biological adhesives for biosurgery, and OutSense, which developed a toilet sensor for early detection of signs of disease. Both of these were sold to large multinational companies. And judging by the sales figures he showed me - he may have another winning product in store.
"We know how to cause the growth of tissues such as skin and bone in the body itself." Ether said. "Our products are based on biological foam. When the foam is inserted into the tissue, it encourages the body's cells to repair and regenerate the tissue in the area. This year a significant income is already expected from a product intended for the treatment of periodontal problems in animals. Next year we expect revenues of several million dollars and it is growing. And now they are also starting to work on aesthetics, plastics - and the lighthouse on the far horizon - the renewal of whole limbs."
The product of an unusual site in the world of tissue engineering, because it comes out at the same time as scientific progress in the field that was published only in the last three years. This progress surprised many in the field, but to the site - which had already released the first BioChange product at the same time - it came by chance, almost as an intervention from above: as a way to explain why its foam is so effective in tissue regeneration.
The science behind the foam
When cells grow in the body, they do so surrounded by an "extracellular matrix": tissue that the cells secrete around themselves. The matrix supports the cells, stabilizes them, allows them to cling to it and even sends them signs and signals that explain to them what they should do in the body. Without the matrix, the cells die or grow in a two-dimensional layer and refuse to function properly.
Tissue engineering companies to date have tried to use matrices that are similar to those that can be found in the adult human. When they wanted to grow a bone, they tried to understand what are the properties of the matrix that is found in the areas of the body where cartilage and bones grow, and then imitate the same structure and properties in an artificial matrix that they produced specifically to be implanted in the body. The cells are supposed to spread into the artificial matrix - and create new, fresh bone tissue inside the body.
This approach makes sense, but it didn't work well. why? No one is safe. But there are guesses.
In 2022, Odetjer Kampas, now a professor of the physics of life at the Technical University of Dresden, published a study that shed light on a possible reason for the difficulty in growing new tissues in the body. Kampas and his colleagues studied the youngest matrix - the one that exists in the fetus when it is still a few weeks old. At this stage, the cells differentiate and migrate to the correct areas where they will divide and produce the body's organs. This fetal matrix is very different from the matrix that can be found in an adult. It is soft and delicate, and mostly resembles foam. Or as Kampas called it - "live foam".
Kampas believes that the mechanical properties of the young matrix, that "living foam", help dictate to cells how they should differentiate and where in space they should migrate in the body. He suggested that we need to understand how the rigidity and hardness of the foam is used to transmit instructions to the cells and affects tissue development in the embryo. He went on to develop computer models to get clues to the way the foam interacts with the cells inside. The research he published reached some of the most well-known science journals - Nature Physics and Nature Materials.
For Ether, these studies were just the icing on the cake, because while Kampas was working on the basic science in his lab, Ether had already produced his own foam, and started implanting it in dogs (and himself).
The dogs first
Dogs, it turns out, suffer from gum disease no less than humans. But unlike humans, biomedical companies do not have to go through long and arduous years of approvals from the FDA to provide dogs with treatment with their product. Approvals are still needed, of course, but nothing compares to the level of proof and investment required for products that are supposed to treat humans.
Is it any wonder that BioChange decided to go to the dogs first?
In the first trial with the product documented in the scientific literature, veterinarians focused on nine dogs that needed gum treatment due to widespread gingivitis that caused severe receding gums. The dogs received normal treatment on one side of the mouth, and on the other side - received the BioChange foam implant.
The results were impressive: in all the teeth where the foam was implanted, fuller growth of the gums around the tooth was evident. There is evidence of bone restoration even in particularly challenging places such as between the roots of the tooth. The BioChange foam was found to be safe to use, and veterinarians reported that it was easy and convenient to incorporate into the treatment. It was a clear success for the company, which resulted in demand and sales of over half a million dollars already this year, and several million more expected next year.
"We get a lot of responses from veterinarians who didn't believe that these teeth could be saved at all. They come back to us to show us their results, and say it's really a miracle for them." Ether said.
And what about humans?
These days the product - named ReGum - is undergoing pre-clinical trials on additional animals. These are experiments that are required of anyone who wants to perform clinical experiments on humans, and they are expected to start next year. The first clinical trials will mainly focus on safety, to make sure that the implant is not harmful to humans.
Ether himself is already convinced of their success. fact. He agreed to implant the foam in his hip.
"It was mainly to find out about safety," he admits with a smile. "I didn't do it to rejuvenate the skin on my thigh. I injected myself only after many, many pre-clinical trials that proved safety. Since the company is mine and I also invest in it, I wanted to demonstrate that everything is fine in humans as well, and to prove to others that this is a really safe substance."
For now, at least, he's still alive. The graft in his hip was filled with young collagen, and no negative physiological reaction was recorded from the surrounding tissues. We can hope that the full pre-clinical trials, followed by the clinical trials on humans, will be completed successfully and quickly, and that we will all be able to benefit from the treatment of periodontal problems already in the coming years.
And much more than that.
The big plan
Ether does not intend to stop with gum problems. As entrepreneurs do, he believes his product can solve, well, almost anything. He shared with me a series of success stories in animals, which may also hint at the potential of the treatment in humans for tissue restoration.
"For example, small animals like Shih Tzu dogs, usually have a hard time dealing with fractures in their delicate jaws." saying. "We discovered that foam can be added into the fracture to restore the bone."
But why stop at the gums? The BioChange foam may still be used for many other treatments.
"A vet came with a horse that suffered from a wound that did not heal." says Ether. "We cleaned the wound and put the foam on it. After that a beginning of improvement was seen. We continued to put the foam on it, and after four months the wound had already closed by itself."
It is recommended to exercise your sense of critical thinking at this point (and whenever you talk to entrepreneurs in general). These are anecdotes, and as the saying goes - "many anecdotes do not constitute science". And yet, they are interesting and may indicate a potential worth examining in a more orderly manner: with experiments whose results will be published in peer-reviewed scientific journals.
Ether understands this need, and showed me the results of trials conducted around BioChange's next product. They intend to concentrate this time on human skin. In the results of the experiments, it appears that the foam graft is optimally filled with fibroblast cells, and these produce young and new collagen in the area where it is implanted under the skin. Why is this important? Because some of the wrinkles on the aging skin are created due to the cumulative damage caused to the 'old' collagen in the skin. Whoever finds a way to smooth out those wrinkles through the creation of young collagen in those areas - will win a market share of billions of dollars in medical treatments.
"So far our successes with simple tissues are quite miraculous." says Ether. "As for more complex applications, like growing maybe even a full hand or arm from scratch - we're not there yet, but it's definitely not science fiction."
Maybe.
The sober look
I've gushed a lot about BioChange here, and I believe they have an interesting product with potential for success. But it is also important to examine them with a more sober eye. It seems that the company is currently mostly focused on trying to develop a product that will work and sell, but there seems to be a lack of a deep theoretical understanding of the exact reason why it works so well.
"We had limited understanding and knowledge about the mechanism of action of the foam. For example, we knew that the huge surface area of the foam makes biological binding sites accessible to the cells," Ether told me. "Finally came the Kampas study, which contributed another very interesting point of view to the picture and an insight into why the product is so successful as it is."
Without an understanding of the theory - without a computer model that explains how the foam behaves and reacts with the cells - it is hard to believe that BioChange will be able to realize the more futuristic vision of Ether.
"Growing a hand or arm from scratch" is not an impossible task. Fact: The humble salamander manages to do this well. But this is a big and impressive challenge that should not be underestimated. It is possible that the "living foam" will be the first step on the way to the restoration of whole limbs, but it probably won't happen like that-just-tomorrow-morning. We will have to better understand how the foam directs the cells in the body of the embryo, and perhaps also in the tips of the regenerating limbs of the salamander. Without such an in-depth understanding, we can at most reconstruct basic tissues - muscle, bone, cartilage and others. We may even be able to restore relatively simple organs, such as a jaw. But to combine several different tissues to recreate a dynamic and functional limb, we will need a higher level of sophistication.
Reference
![These tiny polymer scaffolds include channels 100 micrometers wide, about the width of a human hair. When live cells are added to the content, the channels serve as artificial blood vessels. By mimicking human tissues of organs such as liver and heart, these scaffolds provide an innovative method for testing new drugs with the aim of reducing their dangerous side effects. [Courtesy: Tyler Irving/Boyang Zhang/Kevin Soobrian]](https://www.hayadan.org.il/images/content3/2016/03/Graphic-031.jpg.webp "Engineers have succeeded in growing XNUMXD heart and liver tissues")
