Start-Up Founders Demonstrate Amputated Tissue Regrowth

African clawed frog (Brian Gratwicke, Flickr. https://flic.kr/p/dFHy8R)

31 Jan. 2022. Founders of a regenerative medicine company demonstrated a drug delivery device that helps regrow several tissue types on frogs’ amputated limbs. A team from Tufts University in Medford, Massachusetts, led by researchers that started the company Morphoceuticals Inc., describes its findings in the 26 Jan. issue of the journal Science Advances.

The team led by Tufts researchers Michael Levin, professor of regenerative biology, and biomedical engineering professor David Kaplan, are seeking a process that encourages regrowth of multiple types of tissue on amputated limbs. The authors cite data showing 1.6 million Americans living with limb loss in 2005, with that number expected to grow to 3.6 million by 2050. Leading causes of limb amputations are trauma and war wounds, peripheral artery disease, and complications from type 2 diabetes. Among the 2005 population, more than four in 10 amputees (42%) were non-white.

Levin is director of the Allen Discovery Center at Tufts that studies morphogenesis, the process for generating tissue in shapes and patterns, in this case to build and repair complex anatomies. The field, says the Allen Center, includes embryo development, computational biology, artificial intelligence, and signal processing in groups of cells. Kaplan studies regenerative properties of biomaterials, particularly silk, as they interact with stem cells to form new tissue.

The Tufts team designed a process for delivery of several growth compounds to an amputation site to encourage morphogenesis for regrowing multiple tissue types. To demonstrate the process, the researchers used African clawed frogs, a species known formally as Xenopus laevis, that loses its ability to regenerate new tissue in adulthood.

Biodome device worn for 24 hours

The team delivered a collection of five small-molecule growth factor proteins and compounds for controlling adverse reactions, such as inflammation, to the frogs’ hind-leg amputation sites. The drugs were administered through a bioreactor, called a biodome, worn as a 3-D printed sleeve on the site. The biodome is made with a silk hydrogel that releases the regenerative compounds over time. Each frog amputee wore a biodome for 24 hours. The researchers then tracked tissue growth and repair for 18 months.

The authors report by that time treated frogs regrew bone, and repaired nerves and muscles with integrated blood vessels. The treated frogs also restored sensation and motor nerve pathways and began showing formation of digits at the ends of the limbs. In addition, treated frogs also showed movements over surfaces similar to wild-type frogs.

Levin and Kaplan founded Morphoceuticals Inc. in 2020, as a project of Juvenesence Ltd. a company that starts-up, incubates, and invests in enterprises creating therapies for age-related diseases or technology platforms supporting new treatments. In Aug. 2019, Science & Enterprise reported on Juvenesence, based on the Isle of Man in the U.K., raising $100 million in its second venture funding round.

“These findings,” says Juvenesence CEO Greg Bailey in a statement released through BusinessWire, “herald the first application of a new set of tools that will be further developed by Morphoceuticals and will allow us to explore new approaches to regenerative treatment in ways that are truly unique.” Kaplan adds, “These data demonstrate our ability to successfully kickstart endogenous regenerative pathways in vertebrates. However, translation of these findings to mammals remains to be demonstrated as a next key step in this process.”

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