Hydrogel matrices for the formation of new vessels
Successful application of regenerative therapy methods often requires cultivation in the area of damage to functional blood vessels. Researchers at the Georgia Institute of Technology (Atlanta), working under the guidance of Professor Andres García, have developed a method to solve this problem using biocompatible, decomposing synthetic hydrogels in the body.
As part of their work, the scientists modified the biochemical and mechanical properties of polyethylene glycol matrices so that new vessels could form both around them and throughout the polymer volume. To do this, they created cross–links between the polymer chains, ensuring its stability and breaking down under the action of matrix metalloproteinases - enzymes released by cells inhabiting the matrix.
Adhesive sequences of amino acids were added to the hydrogel to facilitate the spread of the matrix providing angiogenesis of endothelial cells and their interaction with each other.
Vascular endothelial growth factor (VEGF), a protein that stimulates the growth of blood vessels, was also introduced into the gel, and the release of this protein occurred only when the cross–links of the polymer chains were broken. When a soluble form of VEGF was administered to small animals, its concentration in the body decreased evenly; implantation of modified hydrogel matrices ensured the maintenance of a constant level of VEGF for two days, and only after that its concentration began to gradually decrease.
Despite the fact that the difference in the rate of decrease in the concentration of growth factor was small, the images obtained using computed tomography showed that two weeks after implantation, the hydrogel matrix provided six times higher density of newly formed vessels than the introduction of a soluble form of VEGF. Two weeks later, this figure doubled. The vascular network formed inside and around the hydrogel matrix was fully functional. The contrast agent injected into the aorta reached the new vessels without hindrance, which indicates their integration into the circulatory system of the body. The hydrogel in the body gradually degraded and was replaced by normal tissue.
Gel matrices two (left) and four (right) weeks after implantation.
The vascular network gradually grows into the implant from the surrounding tissues.
The authors also developed a liquid material capable of turning into a gel inside the body under the influence of ultraviolet radiation. Such material can be injected into the deep tissues of the body with the help of minimally invasive methods and fill the damage zone of absolutely any shape with it.
Such a liquid material containing VEGF was injected into mice with induced ischemia (impaired blood supply) of one leg. After seven days, the blood supply to the affected leg in animals increased by 1.5, and the affected foot – by 2 times. These results were significantly better than the results of control experiments in which animals were injected with a hydrogel that did not decompose in the body or soluble growth factors.
The authors believe that such a pronounced restoration of blood flow is due to the slow release of the growth factor deposited in the matrix, which occurs as the hydrogel decomposes.
Currently, additional trials are already underway, the purpose of which is to assess the suitability of the new method as a means of treating peripheral artery diseases and coronary heart disease. In the future, the authors plan to test the possibility of introducing more VEGF into the hydrogel or its combination with other growth factors in order to obtain an even more pronounced healing effect.
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the Georgia Institute of Technology: "Growing Blood Vessels: Bioengineered Materials Promote the Growth of Functional Vasculature, New Study Shows".
25.12.2009