This groundbreaking biomaterial heals tissues from the inside out
The material can be injected intravenously and has potential application
in heart attacks, traumatic brain injury and more

Date:
January 30, 2023
Source:
University of California - San Diego
Summary:
A new biomaterial that can be injected intravenously, reduces
inflammation in tissue and promotes cell and tissue repair. The
biomaterial was tested and proven effective in treating tissue
damage caused by heart attacks in both rodent and large animal
models.

Researchers also provided proof of concept in a rodent model that
the biomaterial could be beneficial to patients with traumatic
brain injury and pulmonary arterial hypertension.


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FULL STORY ==========================================================================
A new biomaterial that can be injected intravenously, reduces inflammation
in tissue and promotes cell and tissue repair. The biomaterial was tested
and proven effective in treating tissue damage caused by heart attacks
in both rodent and large animal models. Researchers also provided proof
of concept in a rodent model that the biomaterial could be beneficial to patients with traumatic brain injury and pulmonary arterial hypertension.


========================================================================== "This biomaterial allows for treating damaged tissue from the inside out,"
said Karen Christman, a professor of bioengineering at the University of California San Diego, and the lead researcher on the team that developed
the material.

"It's a new approach to regenerative engineering." A study on the safety
and efficacy of the biomaterial in human subjects could start within
one to two years, Christman added. The team, which brings together
bioengineers and physicians, presented their findings in the Dec. 29
issue of Nature Biomedical Engineering.

There are an estimated 785,000 new heart attack cases in the United
States each year, and there is no established treatment for repairing the resulting damage to cardiac tissue. After a heart attack, scar tissue
develops, which diminishes muscle function and can lead to congestive
heart failure.

"Coronary artery disease, acute myocardial infarction, and congestive
heart failure continue to be the most burdensome public health problems affecting our society today," said Dr. Ryan R. Reeves, a physician in the
UC San Diego Division of Cardiovascular Medicine. "As an interventional cardiologist, who treats patients with coronary artery disease and
congestive heart failure on a daily basis, I would love to have another
therapy to improve patient outcomes and reduce debilitating symptoms."
In previous studies, the team led by Christman developed a hydrogel
made from the natural scaffolding of cardiac muscle tissue, also known
as the extracellular matrix (ECM), that can be injected into damaged
heart muscle tissue via a catheter. The gel forms a scaffold in damaged
areas of the heart, encouraging new cell growth and repair. Results
from a successful phase 1 human clinical trial were reported in fall
2019. But because it needs to be injected directly into heart muscle,
it can only be used a week or more after a heart attack -- sooner would
risk causing damage because of the needle-based injection procedure.

The team wanted to develop a treatment that could be administered
immediately after a heart attack. This meant developing a biomaterial
that could be infused into a blood vessel in the heart at the same
time as other treatments such as angioplasty or a stent, or injected intravenously.

"We sought to design a biomaterial therapy that could be delivered to difficult-to-access organs and tissues, and we came up with the method
to take advantage of the bloodstream -- the vessels that already supply
blood to these organs and tissues," said Martin Spang, the paper's first author, who earned his Ph.D. in Christman's group in the Shu Chien-Gene
Lay Department of Bioengineering.

One advantage of the new biomaterial is that it gets evenly
distributed throughout damaged tissue, because it's infused or injected intravenously. By contrast, hydrogel injected via a catheter remains in specific locations and doesn't spread out.

How the biomaterial is made Researchers in Christman's lab started with
the hydrogel they developed, which was proven to be compatible with
blood injections as part of safety trials. But the particle size in the hydrogel was too big to target leaky blood vessels.

Spang, then a Ph.D. student in Christman's lab, solved this issue by
putting the liquid precursor of the hydrogel through a centrifuge, which allowed for sifting out bigger particles and keeping only nano-sized
particles. The resulting material was put through dialysis and sterile filtering before being freeze dried. Adding sterile water to the final
powder results in a biomaterial that can be injected intravenously or
infused into a coronary artery in the heart.

How it works Researchers then tested the biomaterial on a rodent model
of heart attacks.

They expected the material to pass through the blood vessels and into the tissue because gaps develop between endothelial cells in blood vessels
after a heart attack.

But something else happened. The biomaterial bound to those cells,
closing the gaps and accelerating healing of the blood vessels, reducing inflammation as a result. Researchers tested the biomaterial in a porcine
model of heart attack as well, with similar results.

The team also successfully tested the hypothesis that the same biomaterial could help target other types of inflammation in rat models of traumatic
brain injury and pulmonary arterial hypertension. Christman's lab will undertake several preclinical studies for these conditions.

Next steps "While the majority of work in this study involved the heart,
the possibilities of treating other difficult-to-access organs and
tissues can open up the field of biomaterials/tissue engineering into
treating new diseases," Spang said.

Meanwhile, Christman along with Ventrix Bio, Inc., a startup she
cofounded, are planning to ask for authorization from the FDA to
conduct a study in humans of the new biomaterial's applications for
heart conditions. This means that human clinical trials begin in be one
or two years.

"One major reason we treat severe coronary artery disease and myocardial infarction is to prevent left ventricular dysfunction and progression
to congestive heart failure," said Dr. Reeves. "This easy-to-administer
therapy has the potential to play a significant role in our treatment approach."
* RELATED_TOPICS
o Health_&_Medicine
# Heart_Disease # Stroke_Prevention # Vioxx
o Plants_&_Animals
# Biotechnology_and_Bioengineering # Veterinary_Medicine
# Developmental_Biology
o Matter_&_Energy
# Medical_Technology # Biochemistry # Nanotechnology
* RELATED_TERMS
o Cerebral_contusion o Plant_cell o Traumatic_brain_injury o
Meat o Brain_damage o Hypertension o Necrosis o Healing

========================================================================== Story Source: Materials provided by
University_of_California_-_San_Diego. Original written by Ioana
Patringenaru. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Martin T. Spang, Ryan Middleton, Miranda Diaz, Jervaughn Hunter,
Joshua
Mesfin, Alison Banka, Holly Sullivan, Raymond Wang, Tori
S. Lazerson, Saumya Bhatia, James Corbitt, Gavin D'Elia, Gerardo
Sandoval-Gomez, Rebecca Kandell, Maria A. Vratsanos, Karthikeyan
Gnanasekaran, Takayuki Kato, Sachiyo Igata, Colin Luo, Kent
G. Osborn, Nathan C. Gianneschi, Omolola Eniola-Adefeso, Pedro
Cabrales, Ester J. Kwon, Francisco Contijoch, Ryan R. Reeves,
Anthony N. DeMaria, Karen L. Christman.

Intravascularly infused extracellular matrix as a biomaterial
for targeting and treating inflamed tissues. Nature Biomedical
Engineering, 2022; DOI: 10.1038/s41551-022-00964-5 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2023/01/230130144805.htm

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