Researchers led by Xingyu Jiang, a researcher at Southern University of Science and Technology and the National Center for NanoScience and Technology in China, have developed a next generation biocompatible, flexible, degradable Tissue Engineered Blood Vessels (TEBV), electronic blood vessels, which can mimic natural blood vessels. In this scientific breakthrough the researchers from Switzerland and China have integrated comprehensive electrical functions on a conventional TEBV thus paving way for a novel treatment approach for cardiovascular diseases.
Cardiovascular disease, caused by accumulation of fatty deposits inside the arteries and an increased risk of blood clots, is one of the main causes of death globally. The current treatment is Coronary Artery Bypass Grafting (CABG). CABG is used to bypass the blocked coronary artery (tiny blood vessel which supplies oxygen rich blood to the heart). A healthy artery or vein from the patient’s body (autologous) is grafted to the blocked coronary artery in order to bypass the blocked part of the coronary artery. However the dearth of suitable autologous heart or vein in some patients has led to difficulties in treating cardiovascular diseases. In such cases synthetic graft material are used. Synthetic blood vessels do not match autologous blood vessels in performance and has a number of limitations. Moreover they are not suitable to treat blood vessels with smaller diameter. Tissue engineered blood vessels (TEBV) is thought to provide the optimal solution for this problem. Tissue engineering is the combined interdisciplinary approach of engineering, material science and biology which is being used to develop biological substitutes that will restore, maintain or improve tissue or organ function. The development of TEBV is of immense importance to researchers due to its potential application in the treatment of cardiovascular diseases.
Previously developed Tissue engineered blood vessels (TEBVs) to treat blockages of tiny blood vessels have a number of limitations:
- Most of them merely serve as a passive scaffold to provide mechanical support to the tiny blood vessels which are difficult to treat.
- They cannot assist in regeneration of new blood vessel tissues.
- They often lead to inflammatory response and its associated complications.
Thus none of the existing small diameter (<6mm) TEBVs have met the clinical demands of treating cardiovascular diseases.
The researchers led by Xingyu Jiang have equipped the conventional biodegradable TEBV with electrical functions thus bioengineering a novel platform for the treatment of complications associated with small diameter blood vessels.The next generation TEBV, electronic blood vessels, bioengineered by the researchers has overcome the limitation of its predecessor. The scientist used a cylindrical rod to roll up metal polymer conductor membrane to develop a biocompatible electronic blood vessel that can integrate flexible electronics with three layers of blood-vessel cells, to imitate and perform functions beyond the capacity of natural blood vessel. By coordinating with electronic devices, the electronic blood vessel can provide various additional treatments such as electrical stimulation, electrically controlled drug release, gene therapy. The ingenious electronic vessels upon electrical stimulation could facilitate the formation of new endothelial blood vessel tissue. These additional functions make the electronic blood vessels far more superior than the existing conventional TEBV.
In order to test the effectiveness of the electronic blood vessel the scientists performed in vitro experiments in the lab:
- Electrical stimulation from the electronic blood vessels induced rapid multiplication and migration of cells in a wound healing model which indicates that the electronic blood vessel can play an important role in formation of new endothelial blood vessel tissues.
- An electroporation device was also fitted into the blood vessel which applies an electric field to make the cell more permeable. The researchers observed that the blood vessel was capable of delivering green fluorescent protein (GFP) DNA to three kinds of blood vessels in vitro making the blood vessels potent for gene therapy.
After performing the in vitro tests the research team tested the efficacy and biosafety of the electronic blood vessel in an animal model for a period of three months. The carotid artery (artery which supply blood to the brain, neck and face) of rabbits was replaced by the electronic blood vessel.
- With help of ultrasound the scientists observed that the electronic blood vessel could supply sufficient blood.
- With the help of X-ray imaging techniques the researchers observed that the electronic blood vessel could function just like a natural blood vessel and did not show signs of narrowing.
- After the three months of study the researchers removed the artificial blood vessel and studied the internal organs of the rabbits. They did not find any evidence of inflammatory response.
These electronic blood vessels showed promising results in the animal model as claimed by the researchers. According to the researchers they took the conventional TEBV to the next level by integrating flexible bioelectronics which can provide an enhanced treatment for cardiovascular disease. Previously developed small diameter TEBV is not capable of meeting the clinical demands of treating cardiovascular diseases. The researches in this study have developed a biocompatible, flexible, degradable electronic blood vessel by combining metal- polymer conductor with US FDA approved biodegradable polymer. This novel artificial blood vessel can also promote generation of new endothelial blood vessel tissues, is capable of gene therapy and controlled drug delivery.
The research team has emphasized further research work is still required to make this electronic blood vessel available for human trials. Future work would include long term biosafety and efficacy tests in a large group of animal models. Also the researchers feel that for long term suitability the electronic blood vessel needs to be fitted with a smaller electronic device rather than the electroporation device used in this study to generate electrical field. Future work will also include further optimization of the blood vessels by incorporating minimized devices such as minimized batteries and built-in control system so that all the functional parts of this device will be fully implantable and fully biodegradable in the body.
The researchers are also optimistic that one day this device could be paired with artificial intelligence to collect and store detailed data of an individual’s blood glucose level, blood velocity and blood pressure which will pave way for personalized medicines. This technology of combining living tissues with flexible electronics will bestow the conventional TEBV with additional capabilities and functionalities which will revolutionize precision diagnostics.
Shiyu Cheng, Chen Hang, Li Ding, Liujun Jia, Lixue Tang, Lei Mou, Jie Qi, Ruihua Dong, Wenfu Zheng, Yan Zhang, Xingyu Jiang. Electronic Blood Vessel. Matter, 2020; DOI: 10.1016/j.matt.2020.08.029