Method for 3D printing of vascularized tissues and organs
The 3D printing method disclosed here for the production of vascularized tissues and organs requires a droplet printer to produce photorealistic high-resolution prints and a device for applying non-directional or directional electromagnetic waves. The process uses a new type of capillary ink that crosslinks or undergoes a layer-forming reaction only in the edge area of the ink drops. Unbound capillary ink components are removed. The resulting cavities form a capillary network with diameters of up to approx. 10 μm. Also disclosed is a novel printer table for supplying the printed tissue with medium during printing and a printer head supply unit for individually mixing the bio-inks from cell concentrate and various ink concentrates.
1 . A 3D printing process for the production of tissues and organs having vascular structures by means
(a) a droplet printer for photorealistic high-resolution prints and
(b) a device for applying electromagnetic waves
comprising:
providing at least one bio-ink and one capillary ink with cells and cross-linking molecules in the droplet printer;
placing at least one drop of the bio-ink and the capillary ink on one reaction plane;
bringing the electromagnetic waves into contact with the crosslinking molecules in these drops at the reaction level; and
activating of the cross-linking molecules by means of non-directional or directed movements of the electromagnetic waves in the drops, whereby cross-linked structures are formed and vascular structures are thus obtained; and
wherein the capillary inks crosslink or form a layer only in the edge area of the drop at a border to drops of the bio-ink
such that a cavity for the vascular structures is formed,
wherein the crosslinking or layer-forming reactions in the edge area of capillary ink droplets are caused by components in the inks without requiring an addition of a selective factor during printing,
wherein the capillary ink comprises endothelial cells and at least one of crosslinkable molecules, layer forming molecules, or a combination thereof, and
wherein after a cross-linked structure or layer structures have reached a certain height cross-linking molecules, unbound molecules and cells that are non-crosslinked or unbound are eliminated in recurring cycles.
2 . The method according to claim 1 ,
characterized in that
the drop size is between 1 fl (femtoliter) and 1 μl (microliter).
3 . The method according to claim 1 ,
characterized in that
reactions in the edge area of the capillary inks are caused by: thiolene reactions, cycloadditions, nucleophilic ring openings, self-assembly of molecules and particles, or selective factors on the cells of the capillary inks and/or bioinks.
4 . The method according to claim 1 ,
characterized in that
the bioinks include molecules that support the physiology of the printed tissue or organ.
5 . The method according to claim 1 ,
characterized in that
the bioinks contain growth factors, transcription factors, signaling molecules, marker molecules and/or target molecules for later key-lock reactions.
6 . The method according to claim 1 ,
characterized in that
culture medium or blood flows through the printed vascular structures during printing.
7 . The method according to claim 1 ,
characterized in that
the reaction plane is positioned in a bioreactor, which is connected to a blood circuit, during or after the end of a pressure of the blood circuit.
8 . The method according to claim 1 ,
characterized in that
the device for applying the electromagnetic waves is a UV lamp, a diode, a screen or a laser beam device.