Combination of 3-D-print and multiphoton polymerization
Three dimensional objects can be generated flexibly using 3-D-inkjet-printing. The printer applies the material layers according to a CAD file and each layer is than chemically crosslinked using UV radiation. The 3-D-printing technique generates sub-micrometer structures in reasonable production times, yet for the very fine structure of artificial capillaries the printing technology is still too imprecise. Therefore, the scientists combine this method with multiphoton polymerization: This technique generates short intensive laser pulses, that stimulate crosslinking of the precursor molecules in very well defined small volumes of the material. This reaction can be specifically directed so that the construction of finest structures is possible according to a three dimensional blue print. Depending on the chemical material composition the elasticity of the material can be adjusted according to natural blood vessels
For biologization of synthetic tube systems endothelial cells (the cells that cover natural blood vessels in the body) will be connected to artificial vessels. In the first step, biofunctionalization of the artificial material is achieved by chemically coupling of biopolymers (e.g. heparin), and specific cell anchor peptides to the polymer surface in order to promote endothelial cell adhesion. The chemical coupling of biofunctional components is also important with respect to future applications of the artificial blood vessels as medical vascular grafts, because then the formation of blood clots (thrombogenecity) has to be strictly prevented.
Hybrid resins from synthetic and biologic polymers
As an alternative to the biofunctionalization of the finished synthetic tubes by coating, a new class of materials is developed: hybrid materials composed of crosslinkable synthetic and biological polymers are designed to constitute novel “bio-inks”: These are printable and cytocompatible resins with integrated cell adhesion anchor-groups for direct biomaterial processing using additive manufacturing techniques.
Bioreactor for biomimetic blood vessels
The generation of a functional endothelial lining is essential for mimicking the biofunctionality of blood vessels: The endothelial cell layer avoids blood clotting, acts as selective barrier in native blood vessels, and initiates neoangiogenesis by the formation of new capillaries that sprout from an existing blood vessel. Therefore, future application of vascularized tissue models as in vitro testing systems for pharmaceuticals or chemicals require an intact endothelial cell layer. An important step in the cultivation of functional endothelial cells is to imitate the conditions in the body. For this purpose Fraunhofer develops a special bioreactor system where artificial vessel systems that are populated with endothelial cells are dynamically cultivated.
Manufacturing of artificial blood vessel systems will contribute to the development of complex bio-artificial organs. These can be applied for in vitro testing of pharmaceuticals and chemicals and can thus help to reduce animal experiments. As a long-term objective such bioartifical tissues may also be used as implants and can then be connected directly to the patients’ blood circulation to be supplied with nutrients. In addition, the treatment of bypass patients with artificial small caliber vascular grafts is feasible using the new materials and freeform fabrication techniques.