New Hydrogel Features Enhanced Capabilities for Treating Aneurysms and Halting Progression
Posted on 27 Mar 2024
Aneurysms can develop in blood vessels in different body areas, often as a result of atherosclerosis, infections, inflammatory diseases, and other risk factors. These conditions lead to chronic inflammation, causing the cells lining the inside of blood vessels to produce an overabundance of enzymes known as matrix metalloproteinases (MMPs). These MMPs break down the fibers in the vessel walls, weakening them and potentially causing them to bulge outward, creating a risk of fatal rupture. Particularly, aneurysms in the aorta, the largest artery in the body, represent the second most common type of aortic disease and are a significant cause of death globally. Patients experiencing symptoms or rapid growth of an aneurysm are encouraged to seek treatment, with minimally invasive approaches recommended for those with comorbidities or at risk from open surgery.
Traditionally, aneurysms are treated non-invasively by inserting a stent graft to reinforce the vessel walls and prevent blood from entering the aneurysm. However, this method can fail due to leaks between the stent graft and the endothelial wall, which can allow blood to re-enter the aneurysm. To address these leaks, known as endoleaks, embolic agents are used, but they can be expensive, challenging to apply, and sometimes ineffective, often requiring further procedures. Now, scientists at the Terasaki Institute for Biomedical Innovation (TIBI, Los Angeles, CA, USA) have created an innovative, injectable shear-thinning hydrogel for the treatment of abdominal aortic aneurysms that not only more effectively seals them off but also halts their growth.
This embolic agent was formulated using a gelatin-based shear-thinning hydrogel that solidifies upon injection, enhanced with silicate nanoplatelets for improved cohesion and blood clotting. Additionally, it incorporates doxycycline (DOX), an FDA-approved drug known for eliminating dysfunctional endothelial cells and neutralizing MMPs. DOX achieves this through both an immediate burst release for rapid cell removal and a sustained release for long-term MMP inhibition. This dual-action process was validated in animal studies using the new hydrogel in pig aorta samples.
Further experiments showed that adding doxycycline improved the hydrogel's injectability, cohesion, and embolic strength, reducing clotting time by 33%. The new hydrogel also succeeded in embolization in a laboratory model of endoleaks and was shown to impact the expression of various proteins critical to endothelial cell function, blood vessel development, and clot formation. These results suggest the potential for using this novel hydrogel to treat aneurysms elsewhere in the body and highlight the need for further studies on its long-term safety and effectiveness.
“The work here represents a significant advancement in the treatment of aneurysms,” said Ali Khademhosseinini, Ph.D., TIBI’s Director and CEO. “It is our hope that this work can be expanded into further tests and clinical trials so that we may bring this technology to the patients.”
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