One month after Russia launched a full-scale military invasion of Ukraine on February 24, 2022, US regenerative medicine company Humacyte began receiving calls from Ukrainian surgeons.
In the heat of battle, the surgeons were struggling to treat patients that had sustained vascular injuries and were looking to Humacyte’s human acellular vessels or HAVs as a potential solution.
Founded in 2004, the company uses a platform technology to bioengineer replacement human blood vessels that can be used to treat vascular trauma. Although the product is still in clinical trials, more than 430 patients have been implanted with HAVs and early clinical data is encouraging.
The replacement vessels are grown by seeding human donor tissue onto a biocompatible, biodegradable polymer mesh in a bioreactor bag. Over eight weeks, the cells grow and create new tissue, forming a tube-shaped vessel structure while the polymer mesh degrades. The HAV in the bioreactor bag can then be shipped and stored for up to 18 months under normal refrigeration.
Once implanted into the body, the patient’s own cells infiltrate the HAVs and over time, the cells produce multiple layers of living tissue to transform the acellular HAV into a functional, living blood vessel.
Between March and June of 2022, Humacyte coordinated with the U.S. FDA and the Ukrainian Ministry of Health for permission to provide the vessels to Ukrainian patients on a humanitarian basis. So far, surgeons have implanted the HAVs in 10 patients at different locations.
“Most of the patients that received the HAVs are victims of bullet or blast injuries where shrapnel caused arterial damage. There are also crash injuries where people fell from a great height and damaged their lower extremities,” Shamik Parikh, chief medical officer of Humacyte told Medical Device Network. “The follow up data we have that is available indicates that all surgeries have been successful in establishing blood supply and that the HAVs were successfully implanted.”
In one patient case, a 26-year-old male presented with a shrapnel injury to the upper shoulder due to a mine blast which caused severe damage to his brachial artery. “The brachial artery was reconstructed with the HAV, and the patient was discharged without incident,” said Ukrainian surgeon Oleksandr Sokolov. “At a 3-month follow up, the patient is doing well and had no infections.”
If long term data is successful, Humacyte’s HAVs could be revolutionary for the field of trauma repair. Options for vascular reconstruction are currently limited to autologous vein or synthetic conduits. Although autologous vein is preferable, it requires time to harvest and is not always available. Synthetic grafts are also associated with thrombotic complications and are poorly resistant to infection.
“What’s unique about our blood vessels, in addition to being grown from cells, is that after we grow the vessels, we decellularise them,” explained Laura Niklason, MD, CEO of Humacyte. “We remove the cells that are in the engineered tissue and what’s left behind is really the extracellular matrix. As the cellular components are removed, it then becomes a non-immunogenic implant so we can put this into any patient without immune rejection. What we see from the results in Ukraine is that the HAV has been vital for providing blood flow and restoration of function to injured limbs in multiple patients and this restoration of blood supply has allowed all of them to avoid amputation.”
Headquartered in Durham, North Carolina, Humacyte’s manufacturing space is reported to be capable of an annual production capacity of 40,000 HAVs through its LUNA200 bioreactor system. In an October 2022 investor note, financial writer Bret Jensen highlighted how the technology has ‘intriguing potential’.
“The company does not face any late-stage clinical competition for its HAV technology, instead it is trying to simply overcome established autologous vein harvests and synthetic grafts. This market dynamic will work in Humacyte’s favor as its trials are slow to enroll,” wrote Jensen.
The products are the first to receive a Regenerative Medicine Advanced Therapy (RMAT) designation from the U.S. FDA and an FDA Fast Track designation for the creation of vascular access for performing hemodialysis. Humacyte said it is aiming to file a Biologics License Application (BLA) for vascular trauma in mid-2023, followed by a BLA submission in arteriovenous access for hemodialysis.
According to an analysis from the war in Afghanistan, the rate of vascular injury in modern combat is 5 times higher than reported in previous wars and methods of reconstruction are now applied to nearly half of the vascular injuries.
“Military wounds offer a lot of unique challenges as they are often laden with soil organisms making them prone to infections, then there are challenges with moving the patient and limitations to resuscitate and perform vascular reconstruction,” explained Charles Fox, M.D., Ph.D, a retired U.S. Army Lieutenant Colonel and former program director for vascular surgery training at Walter Reed Army Medical Center.
As the war in Ukraine approaches a second year, surgeons and healthcare professional will desperately require treatments that can be applied in increasingly austere and resource limited healthcare settings. Since the war began, it is suspected there have been hundreds of thousands of casualties, with the Office of the UN High Commissioner for Human Rights (OHCHR) reporting 18,096 civilian casualties which includes 6,952 killed and 11,144 injured.
Many Ukrainian surgeons are asking if they can join Humacyte’s ongoing clinical trials, according to Parikh. “We’ve also heard from some of the surgeons that they may be interested in other humanitarian applications, for example, in patients with severe peripheral vascular disease who are at risk of limb loss, or patients who are on dialysis who need vascular access,” said Parikh.
“Although we have studied the HAV in these indications in the US and Europe, it remains to be seen if we’ll expand the use of the HAV to other indications in Ukraine. It’s a very unstable situation so we need to think carefully about how we move forward but surgeons are certainly expressing a lot of enthusiasm in using HAV in other settings.”