Ceramic-containing bioactive inks and printing methods for tissue engineering applications

Abstract

Ink formulations comprising bioactive particles, methods of printing the inks into three-dimensional (3D) structures, and methods of making the inks are provided. Also provided are objects, such as tissue growth scaffolds and artificial bone, made from the inks, methods of forming the objects using 3D printing techniques, and method for growing tissue on the tissue growth scaffolds. The inks comprise a plurality of bioactive ceramic particles, a biocompatible polymer binder, optionally at least one bioactive factor, and a solvent.

What is claimed is: 
     
         1 .- 20 . (canceled) 
     
     
         21 . A solvent-based ink comprising: bioactive ceramic particles; a biocompatible polymer binder; and at least one solvent, wherein the ink comprises at least 70 weight percent of the bioactive ceramic particles, based on the total combined weight of the bioactive ceramic particles and the biocompatible polymer binder and the ink is extruded at room temperature with the solvent evaporated upon extruding, forming one or more porous fibers comprising a microstructure comprising a continuous matrix of the biocompatible polymer binder with intra fiber pores and the bioactive ceramic particles dispersed throughout the microstructure. 
     
     
         22 . The ink of  claim 21 , further comprising at least one bioactive factor. 
     
     
         23 . The ink of  claim 21 , wherein the biocompatible polymer binder is a degradable polyester and the bioactive ceramic particles are comprised of hydroxyapatite, tricalcium phosphate, or a combinations thereof. 
     
     
         24 . The ink of  claim 21 , wherein the bioactive ceramic particles are hydroxyapatite particles and the ink comprises at least 80 weight percent of the hydroxyapatite particles, based on the total combined weight of the hydroxyapatite particles and the polycaprolactone. 
     
     
         25 . The ink of  claim 21 , wherein the biocompatible polymer comprises polylactic-co-glycolic acid, polylactide-co-glycolide, or polycaprolactone. 
     
     
         26 . The ink of  claim 25 , wherein the bioactive ceramic particles are hydroxyapatite particles and the ink comprises at least 80 weight percent of the hydroxyapatite particles, based on the total combined weight of the hydroxyapatite particles and the polylactic-co-glycolic acid, polylactide-co-glycolide, or polycaprolactone. 
     
     
         27 . The ink of  claim 22 , wherein the at least one bioactive factor selected from the group consisting of proteins, peptides, growth factors, genes, pharmaceutical compounds, antibiotics and combinations thereof. 
     
     
         28 . The ink of  claim 21 , comprising at least 90 weight percent of the bioactive ceramic particles, based on the total combined weight of the bioactive ceramic particles and the biocompatible polymer binder. 
     
     
         29 . The ink of  claim 21 , further comprising at least one bioactive factor without heat induced degradation. 
     
     
         30 . The ink of  claim 21 , comprising at least 80 weight percent of the bioactive ceramic particles, based on the total combined weight of the bioactive ceramic particles and the biocompatible polymer binder. 
     
     
         31 . The ink of  claim 21 , wherein the ink is characterized in that it can be extruded as a continuous flexible fiber through a 3D printer nozzle having a diameter in the range from 100 μm to 400 μm using a pressure in the range from 6.2 bar to 4 bar and a printing speed in the range from 4 mm/s to 8 mm/s at a temperature in the range from 22° C. to 40° C. 
     
     
         32 . The ink of  claim 21 , wherein the solvent comprises a high volatility solvent, a secondary surfactant solvent having a vapor pressure lower than the high volatility solvent, and a plasticizer. 
     
     
         33 . The ink of  claim 21 , wherein the solvent comprises a mixture of dichloromethane, 2-butoxyethanol, and dibutylphthalate. 
     
     
         34 . The ink of  claim 21 , wherein the bioactive ceramic particles include bioactive ceramic particles having diameters in the range from 5 μm to 20 μm. 
     
     
         35 . The ink of  claim 21 , characterized in that it can be extruded as a continuous elastic fiber through a nozzle, wherein the elastic fiber can be elastically deformed by a compressive load and then return to its original shape upon unloading. 
     
     
         36 . The ink of  claim 21 , wherein the ink is characterized in that it can be extruded as a continuous flexible fiber through a 3D printer nozzle having a diameter equal to or greater than 100 μm. 
     
     
         37 . The ink of  claim 21 , wherein the ink is characterized in that it can be extruded as a continuous flexible fiber having a diameter of about 200 μm through a 3D printer nozzle. 
     
     
         38 . The ink of  claim 21 , wherein the ink is characterized in that it can be extruded as a continuous flexible fiber through a 3D printer nozzle having a diameter equal to or greater than 400 μm. 
     
     
         39 . The ink of  claim 21 , wherein a diameter of the intra fiber pores are in a range from about 1 μm to about 10 μm. 
     
     
         40 . The ink of  claim 21 , wherein the biocompatible polymer binder comprises an elastomeric polymer. 
     
     
         41 . The ink of  claim 21 , wherein the biocompatible polymer binder comprises a biodegradable polymer. 
     
     
         42 . A solvent-based ink comprising: bioactive ceramic particles; a biocompatible polymer binder; and at least one solvent, wherein the ink comprises at least 70 weight percent of the bioactive ceramic particles, based on the total combined weight of the bioactive ceramic particles and the biocompatible polymer binder, the biocompatible polymer binder makes up from 10 weight percent to 30 weight percent of the combined weight of the bioactive ceramic particles and the biocompatible polymer binder, and the ink is extruded at room temperature with the solvent evaporated upon extruding, forming one or more porous fibers comprising a microstructure comprising a continuous matrix of the biocompatible polymer binder with intra fiber pores and the bioactive ceramic particles dispersed throughout the microstructure.