Injectable Scaffolding Gel Improves Regeneration of Blood Vessels and Muscle Tissue

Researchers have demonstrated that introducing a gel scaffold material of the type used in tissue engineering into living tissues can improve the ability to regenerate at some forms of injury and compensate for some forms of age-related degeneration. Here they test this approach on peripheral artery disease, in which narrowing of major blood vessels due to atherosclerosis means insufficient oxygen and nutrients are delivered to tissues. This causes a wide range of dysfunction, leading eventually to critical limb ischemia and amputation or worse. Spurring tissue regrowth and remodeling via the introduction of scaffolding material doesn't address the underlying causes of the condition, the harmful processes that generate fatty deposits inside blood vessel walls that narrow them, but it can partially compensate by spurring adaptation and increased blood vessel size:

Bioengineers and physicians have developed a potential new therapy for critical limb ischemia, a condition that causes extremely poor circulation in the limbs. The therapy consists of injecting in the affected area a gel derived from the natural scaffolding, or extracellular matrix, in skeletal muscle tissue. The team tested the procedure in a rat model of the disease and found that it promotes muscle remodeling and improves blood flow.

Researchers had already shown that injection of a gel derived from cardiac muscle tissue extracted from pigs could help repair the heart after a heart attack. The tissue is stripped of cells, leaving behind a scaffold of the extracellular matrix from cardiac muscle, which acts a regenerative environment where cells can grow again. Using this same concept, the team now are turning their attention to peripheral artery disease and critical limb ischemia. They developed a material that was derived from the skeletal muscle of pigs to treat damaged skeletal muscle in these patients. Researchers injected the gel into the affected area in a rat model of the disease seven days post-surgery and monitored blood flow in the rats' limbs up to 35 days after injection. Researchers found that the hydrogel increased the diameter of the rats' larger blood vessels, called arterioles. The increased diameter led to improved blood flow in the limbs. By day 35, the size and structure of muscle fibers in the rats treated with the hydrogel was comparable to that in healthy rats.

The gel, which forms a fibrous scaffold upon injection, also attracted muscle stem cells to the affected area. Gene expression analysis showed that inflammatory response and cell death decreased while blood vessel and muscle development pathways increased in rats injected with the gel. Next steps include looking at other disease models in animals and refining preclinical safety protocols and quality control for manufacturing.



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