MSGID: 1:317/3 63d8996e   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    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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