Injectable microtissue preserves muscle function in rats with severed
sciatic nerves

Date:
April 6, 2022
Source:
University of Pennsylvania School of Medicine
Summary:
Researchers engineered the first injectable microtissue containing
motor and sensory neurons encased in protective tissue, called
tissue engineered neuromuscular interfaces (TE-NMIs). The TE-NMI
neurons provide a source of axons to muscles in rats who suffered
nerve injuries, and 'babysit' the muscles to prevent degeneration
and loss of function, while the damaged nerve regrows.



FULL STORY ========================================================================== Researchers engineered the first injectable microtissue containing motor
and sensory neurons encased in protective tissue, called tissue engineered neuromuscular interfaces (TE-NMIs). The TE-NMI neurons provide a source
of axons to muscles in rats who suffered nerve injuries, and "babysit"
the muscles to prevent degeneration and loss of function, while the
damaged nerve regrows, according to researchers at the Perelman School of Medicine at the University of Pennsylvania. Their findings were published
in Bioactive Materials.


==========================================================================
The TE-NMIs are comprised of nerve cells encapsulated in a protective
hydrogel, and the entire microenvironment is injected in close proximity
to muscles. This "ship in a bottle" method protects the neurons and
increases the likelihood that a greater quantity of axons will connect
with the muscle and maintain regenerative pathways.

Researchers severed the sciatic nerve in rats, and injected them with
either a TE-NMI or a microtissue without any neurons. In the group that received TE- NMIs, researchers were able to electrically stimulate the
nerve stump being "babysat" by the TE-NMI and record a muscle response
up to five months after the tissue was implanted. No muscle response
was detected in the control group.

"There are hundreds of thousands of patients who undergo surgery to repair nerve injuries every year, and even if a surgeon performs a perfect
procedure, they can't make axons regrow faster than about one inch per
month. For nerve injuries in the upper arm or upper leg, regeneration
could take years; however, the pathway leading to the muscle and the
muscle itself will irreparably degenerate after six to 12 months without connections from axons, resulting in permanent loss of motor and sensory function," said senior author D. Kacy Cullen, PhD, an associate professor
of Neurosurgery. "By increasing the time window for a patient's axons to reconnect to muscle, this research has potential to improve the extent
of recovery for patients without causing further damage." For example, patients who suffer from a brachial plexus injury -- a nerve root avulsion where nerves are pulled away from the spinal cord -- may regain elbow
function, but will likely never regain function of their hand. In these
cases, a neurosurgeon would typically split a healthy nerve near the hand,
and reroute it to stimulate the hand muscles to restore partial function
while the nerve regrows. TE-NMIs would potentially do a more thorough job, without having to damage a patient's healthy nerve, researchers suggest.

"Working closely with clinicians at Penn's Nerve Center, we identified
a potential surgical paradigm that would be most helpful to them and
their patients," said first author Justin Burrell, PhD, a postdoctoral
research fellow in the Department of Neurosurgery and the Institute for Translational Medicine and Therapeutics. "What's more, as we continue
to test and reaffirm our findings, we will continue our partnership with
the Nerve Center to ensure that our research is providing them with the technology they need to provide the best possible care for patients."
This study was primarily supported by the U.S. Department of Defense
(W81XWH- 16-1-0796, W81XWH-19-1-0867), the National Institutes of Health (R44-NS108869, TL1-TR001880), and the Department of Veteran Affairs (I01-BX003748).


========================================================================== Story Source: Materials provided by University_of_Pennsylvania_School_of_Medicine. Note: Content may be
edited for style and length.


========================================================================== Journal Reference:
1. Justin C. Burrell, Suradip Das, Franco A. Laimo, Kritika S. Katiyar,
Kevin D. Browne, Robert B. Shultz, Vishal J. Tien, Phuong
T. Vu, Dmitriy Petrov, Zarina S. Ali, Joseph M. Rosen, D. Kacy
Cullen. Engineered neuronal microtissue provides exogenous
axons for delayed nerve fusion and rapid neuromuscular
recovery in rats. Bioactive Materials, 2022; 18: 339 DOI:
10.1016/j.bioactmat.2022.03.018 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/04/220406101800.htm

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