Three-dimensional printing of organs on a network of carbohydrate microfibers

Experts hope that new achievements in the field of tissue engineering and regenerative medicine in the near future will allow growing organs for transplantation from the patient's own cells, as well as obtaining animal muscle tissue suitable for culinary purposes in laboratory conditions.

Researchers have already learned how to grow two-dimensional structures of various types of tissues, however, one of the difficulties standing in the way of obtaining three-dimensional structures as close to reality as possible is the supply of oxygen and nutrients to cells in the entire volume of grown organs. In the body, organs and tissues are permeated with a complex system of blood vessels, which has not yet been possible to reproduce in the laboratory.

Scientists at the University of Pennsylvania have developed an innovative solution to the problem of blood supply to artificial organs. They demonstrated that three-dimensional structures made of microfibers created with the help of a printer can be used to quickly form a vascular network and improve the functioning of artificial organs and tissues.

The most popular technique for creating artificial tissues is three-dimensional printing, which consists in the formation of separate layers or droplets of cells and gel, which subsequently connect to each other like LEGO blocks.

This method allows you to create complex shapes from various materials, but when working with cells, the formation of a vascular network is an almost impossible task. There are seams between the layers of hollow tubules formed by 3D printing, which can diverge under pressure. More importantly, many types of cells, for example, liver cells, are not able to withstand the process of three-dimensional bioprinting.

To get around this problem, the authors radically changed the traditional approach. Instead of creating a large volume of tissue permeated with hollow tubules of the vascular network, they developed a network of microfibres that mimics the structure of the vascular network and is located inside the mold. Next, they applied a method similar to casting on a smelted model, which has been used for thousands of years to create statues. At the same time, after the cells introduced into the mold form a dense tissue, the mold is removed, and the microfibers dissolve in water. The solution resulting from the dissolution of microfibers flows out of the formed tubules without having a toxic effect on the cells.

The image obtained with the help of a microscope of a three-dimensional matrix printed on a bioprinter designed to create a vascular network.
Photo: Jordan S. Miller

The optimal material for such fibers turned out to be a mixture of carbohydrates consisting of glucose and sucrose with the addition of dextran, which ensures the strength of the three-dimensional structure.

For additional stabilization, the fibers created using the RepRap 3D printer are coated with a thin layer of biodegradable polymer.

After removing the microfibers, a special solution is pumped through the tubules penetrating the formed tissue, which supplies the cells with nutrients and oxygen and removes waste products.

The whole process does not require large time and financial costs and allows researchers to easily implement the results of computer modeling into the procurement of vascular networks in future organs of various configurations.

Moreover, blood vessel cells inserted into cavities formed when microfibers are removed spontaneously form new capillary sprouts, which further increases the nutrient-supplied tissue area.

Testing of the "circulatory system" formed in this way on a gel matrix containing liver cells showed that when pumping through the vessels of a nutrient-rich medium in gel-enclosed hepatocytes, the production of albumin and urea sharply increased, which is an important indicator of the functioning and general condition of liver cells. In addition, the cells located around the tubules that function as blood vessels were characterized by a higher survival rate.

The researchers believe that their proposed approach has a great future in regenerative medicine, however, they note that they have yet to develop a method for integrating vascular tubules with the patient's vessels, as well as learn how to increase the concentration of hepatocytes (and in the future, other cells) in the gel matrix to clinically appropriate levels.

Article by Jordan S. Miller et al. Rapid casting of patterned vascular networks for perfusable engineered three-dimensional tissues is published in the journal Nature Materials.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the University of Pennsylvania:
Penn Researchers Improve Living Tissues With 3D Printed Vascular Networks Made From Sugar.

06.07.2012