Circumcision may soon be fully reversible. That’s the goal of Foregen, a nonprofit organization dedicated to making the first viable bio-engineered foreskin using advanced tissue engineering.
Started as a passion project in 2010 by renowned Italian mosaic artist Vincenzo Aiello and entirely crowdfunded, Foregen is truly an outlier in science – and expects to begin human clinical trials soon.
That is, if they can get to regulatory approval.
It all starts with an eviction
According to a Substack post by Rena Malik, MD, foreskin restoration has ancient roots, having been practiced by the Romans, for whom bared glans were distasteful. The Roman physician Celsus described some foreskin restoration techniques in his medical treatise De medicina, published around 25 CE.
Modern options for circumcision reversal are currently limited, involving surgery or lengthy “stretching” processes. Even then, the results aren’t quite the same as an anatomically authentic foreskin.
What Foregen proposes is a two-fold process. First, a section of foreskin called the prepuce is taken from a medically donated cadaver.
This tiny piece of tissue is then decellularized using chemicals or enzymes, leaving behind an organic scaffold. “Cellular eviction” is what Chief Science Officer William Musa offered when I prompted him for an ELI5 explanation.
“We’re not sending in the police to evict,” Musa told me. “We’re putting the post-its on the wall, and they’re leaving pretty peacefully. And they’re not destroying the property when they leave.”
The decellularized prepuce, which is also known as ghost tissue, is then seeded with the patient’s stem cells, custom-fitted, and surgically attached.
The trick is to strip enough cells so that the ghost tissue lacks any unique identifiers, but not so many that the structure itself is compromised.
Hope or “hopium”?
From its inception, Foregen, a registered 501(3)(C) in the state of California, has relied entirely on donations. Not that they haven’t tried to apply for grants.
“We partnered up with this chemist in Europe and put together an application for grant funding from Novo Nordisk to support a bioprinting project,” Chief Operations Officer Ryan Jones told me.
It was ultimately unsuccessful, but there are more grant opportunities on the horizon.
Cellular bioprinting, which uses a 3D printer-like model to fabricate functional tissue, would solve a problem that Foregen doesn’t have yet: namely, how to provide enough tissue if even a small fraction of the world’s 1.5 billion circumcised people were to decide to undergo surgery to reverse their circumcision.
A small but dedicated number of these people are monthly donors to Foregen, which is operated by a skeleton crew of global independent contractors, volunteers, and a clinical team at Comenius University in Bratislava, Slovakia.
But not all of them are happy.
“For the ones thinking this will be available sometimes soon, it won’t be,” a commenter posted on a recent video uploaded to Foregen’s YouTube page.
This is the common refrain of detractors in niche online communities like Reddit’s r/foreskinrestoration: that Foregen is selling “hopium,” a popular internet portmanteau of the words “hope” and “opium.”
Their critique is that Foregen promises the prompt rollout of cutting-edge medical technology that may take at least another decade to figure out – and a lot more money.
Foregen has been recruiting for human clinical trials since 2010, according to a search on the Wayback Machine. None have materialized yet.
In 2023, Eric Cunningham, Matthew Serody, and Tyler Drozd, Foregen’s Chief Science Officer, Senior Director, and Chief Operations Officer, amicably stepped down to start a company called Akroprint, a scalable, 3D bioprinted solution for foreskin regeneration.
William Musa and Ryan Jones were internally promoted to Chief Science Officer and Chief Operating Officer.
“There was a little bit of a different vision at that point and not necessarily anything negative,” William Musa told me of the early days.
In late 2024, Foregen raised US$100,000 to support preclinical work that would lead to human clinical trials, which they expected to conduct in 2025. But the new leadership decided to shift operations from Italy to Slovakia, where they began a research partnership with Dr. Stanislav Žiaran.
“There were some regulatory hurdles in Italy that were holding us up, and there were some surgical hurdles, and we didn’t feel that we had the right surgeon,” William Musa said to me. “The right talent. To accomplish the quality that we needed.”
The new Foregen is more nimble. But its clinical focus is also different.
In Italy, Foregen had experimented with more standardized recellularization techniques, such as burying skin tissue samples beneath the skin to encourage new cell growth – a process known as suturing.
According to William, Žiaran’s lab can provide everything they need, including a bioreactor, which Foregen anticipates will be the most effective method to boost the patient’s cells to reseed, and ultimately repopulate, the decellularized foreskin with new native tissue, according to a promotional video by Foregen.
Some of Foregen’s struggles have been outside of their control. When war broke out in Ukraine – one of the world’s largest tissue suppliers – it effectively suspended its operations, including histology, decellularization, and animal trials, until it could find another supplier.
The COVID-19 pandemic was another deterrent – particularly for Foregen, whose clinical operations at the time were based in Italy.
As part of their preclinical work, Foregen is experimenting with other recellularization protocols, including traditional biological methods such as cell culturing.
The push and pull of community
Right now, circumcised people who would like their foreskin back don’t have a lot of options. There is a successful, if rarely used surgical technique, which involves creating a skin graft from another part of the body, but that only solves one problem: full glans coverage.
Manual restoration methods, on the other hand, can achieve full glans coverage and restore sensitivity. These methods, however, involve a significant personal commitment: often 2 to 4 years, according to a recent scientific paper, if one sticks to a regimen.
Popular regimens often include a mixture of “tugging,” or manual stretching techniques, and wearing either T-tape or a similar device that keeps the foreskin taut to encourage new skin growth.
Manual methods also have limitations: stretching alone cannot bring back the ridge band or the frenulum, which is often removed during routine infant circumcision.
Some who manually restore get touch-up surgery once they have achieved full glans coverage in order to tighten the skin at the end in order to more closely resemble a natural foreskin and encourage mucosal tissue growth.
For some, one surgery isn’t enough.
An active, enthusiastic, and very online community, those championing foreskin restoration have been largely overlooked in the media. One memorable episode of HBO’s How To With John Wilson featured intactivist Ron Low, the inventor and, until recently, owner of TLC Tugger, a popular restoration device.
Foregen’s unique business model has led to unique problems. Where a corporation has shareholders to answer to, Foregen has donors, many of whom are active members of the foreskin restoration community.
In some ways, the community pushback is built-in.
The foreskin restoration community is united by shared emotional pain, but also mutual accountability. Its glue is the positive reinforcement restorers provide each other online, especially when progress is coming slower than expected, or motivation is waning.
Often, you’ll see a mention of KOT, or Keep On Tugging – in short, to keep putting the work in, no matter how hard it gets.
Dedicated, in their words, “to give circumcised men the chance to reclaim their complete body,” Foregen’s positionality is different from your average biotech company. According to Ryan and William, everyone at the company has a personal connection to the restoration movement, and a vested interest in its success.
“We’re not driven by the profit motive, so we don’t have to take any shortcuts or do anything in the name of making it more profitable at the expense of limiting the robustness of the solution that we ultimately develop,” Ryan Jones said to me. “We want to achieve full regeneration of the tissue as much as is technically possible without compromising.”
You might even call it community-driven medicine. That is, a community has come together to support research to meet a medical need that has been largely ignored by Big Biotech – and hopes there will be results.
Without a parent company or university system, Foregen is tasked with navigating the expensive (and labyrinthine) clinical trial process on their own.
As always, they are cautiously optimistic.
As Foregen prepares for human clinical trials, much remains unknown, including how repigmentation of the decellularized foreskin might work.
You might ask, who would want to be a participant in human clinical trials, anyway? A lot of people, it turns out. Their last open call for volunteers to participate in human clinical trials, for instance, had over 10,000 sign-ups.
Unfortunately for many of them, it is now looking like volunteers for these human clinical trials will have to be sourced locally – either from Slovakia or the European Union at large.
It depends on where the human trials ultimately take place, and what the regulations in said locale are.
And the others? They will do what they have always done. Wait – or tug.
Fact-checked by Mike McRae
