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Hydrogel Injection Tested to Treat Advanced Artery Disease

Freeze-dried matrix

Muscle cell structure matrix in freeze-dried form, before mixing with hydrogel (Jacobs School of Engineering/UC San Diego)

9 March 2016. A biomedical engineering team developed an injected hydrogel for advanced cases of peripheral artery disease that in lab animals improved blood flow and muscles in affected limbs. Researchers from University of California in San Diego, led by bioengineering professor Karen Christman, published their findings earlier this year in the Journal of the American College of Cardiology: Basic to Translational Science.

The UC-San Diego team is seeking more treatment options for critical limb ischemia, an advanced form of peripheral artery disease, where arteries are obstructed, which limits blood flow to hands, feet, and legs. The disorder is caused by a build-up of plaque in the arteries that thickens and narrows arteries, often as a result from smoking, diabetes, obesity, high blood pressure, and other cardiovascular conditions. Critical limb ischemia is considered a serious condition requiring immediate attention, usually by surgery, but left untreated can lead to amputation.

The authors cite data indicating 120,000 people in the U.S. and 100,000 in Europe require amputations from the disease, but as many as 40 percent have no other option to improve blood flow, and those who find ways to reduce obstructions in their arteries still face increased risks of the condition returning later on.

Christman’s lab develops injectable biomaterials for tissue repair and regeneration. Researchers in this case, including colleagues from the university’s medical school, experimented with a hydrogel containing cell structures from natural animal skeletal muscle that can be injected into the affected limbs. Hydrogels are networks of material that contain primarily water, but maintain enough substance to form into 3-D gelatinous structures.

The skeletal cell structures in the gel form a matrix on which muscle cells can grow again. For this study, the researchers extracted the cellular structural matrix from pig skeletal muscles, which were spun in a detergent to remove the cell structure matrix, then freeze-dried and combined with the hydrogel.

The team tested the skeletal muscle-matrix hydrogel in the hind limbs of lab rats surgically induced with critical limb ischemia. One week later, the researchers injected the rats’ affected limbs with the hydrogel, and 35 days after the injections tested functioning and condition of the arteries and surrounding muscles. For comparison, researchers also injected similar rats with a hydrogel containing human umbilical cord matrix and other rats with a saline solution.

The results show rats receiving either the skeletal matrix or umbilical cord matrix hydrogels reduced their artery obstructions, and improved blood flow in the affected limbs. Those receiving the skeletal matrix hydrogel, however, also exhibit muscle tissue size and structure similar to healthy muscle tissue, as well as less inflammation and cell death.

The authors say further testing and refinements in the process, as well as toxicology testing, are needed before human treatments can be developed. But Christman’s lab may benefit from work being done by Ventrix Inc., a company in San Diego co-founded by Christman, commercializing a similar injectable hydrogel derived from pig heart muscles. That hydrogel is currently in an early-stage clinical trial as a treatment for patients who experience heart attacks or heart failure.

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