Engineered tissue constructs

Abstract

A modular engineered tissue construct includes a plurality of fused self-assembled, scaffold-free, high-density cell aggregates. At least one cell aggregate includes a plurality of cells and a plurality of biocompatible and biodegradable nanoparticles and/or microparticles that are incorporated within the cell aggregates. The nanoparticles and/or microparticles acting as a bulking agent within the cell aggregate to increase the cell aggregate size and/or thickness and improve the mechanical properties of the cell aggregate as well as to deliver bioactive agents.

Having described the invention we claim: 
     
         1 - 10 . (canceled) 
     
     
         11 . A modular engineered tissue construct, comprising; 
 a plurality of fused self-assembled, scaffold-free, high-density cell aggregates, wherein at least one cell aggregate includes a plurality of cells and a plurality of biocompatible and biodegradable nanoparticles and/or microparticles that are incorporated within the cell aggregates, the nanoparticles and/or microparticles acting as a bulking agent within the cell aggregate to increase the cell aggregate size and/or thickness and improve the mechanical properties of the cell aggregate.   
     
     
         12 . The modular engineered tissue construct of  claim 11 , wherein the self-assembled, scaffold-free, high-density cell aggregates comprise differing aggregate materials, at least one of the ring-shaped self-assembled, scaffold-free, high-density cell aggregates being provided or formed with or without nanoparticles and/or microparticles and having different properties than the other aggregates to vary the properties of the construct for particular tissue engineering applications. 
     
     
         13 . The modular engineered tissue construct of  claim 11 , wherein the at least one of the fused ring-shaped self-assembled, scaffold-free, high-density cell aggregates comprises a plurality of chondrogenic cells that have been differentiated to form engineered cartilage. 
     
     
         14 . The modular engineered tissue construct of  claim 11 , comprising alternating first engineered ring-shaped self-assembled, scaffold-free, high-density cell aggregates and second engineered ring-shaped self-assembled, scaffold-free, high-density cell aggregates fused to form a heterogenous modular tissue tube. 
     
     
         15 . The engineered modular tissue construct of  claim 14 , wherein the first engineered ring-shaped self-assembled, scaffold-free, high-density cell aggregates define cartilaginous portions within the tube and the second engineered ring-shaped self-assembled, scaffold-free, high-density cell aggregates define noncartilaginous portions within the tube. 
     
     
         16 . The engineered modular tissue construct of  claim 11 , the nanoparticles and/or microparticles comprising a biocompatible and biodegradable polymer. 
     
     
         17 . The engineered modular tissue construct of  claim 11 , the nanoparticles and/or microparticles including at least one bioactive agent that is differentially and/or controllably released by the nanoparticles and/or microparticles. 
     
     
         18 . The engineered modular tissue construct 17, bioactive agent including at least one of TGF-β1 and/or BMP-2. 
     
     
         19 - 28 . (canceled) 
     
     
         29 . An engineered trachea implant comprising:
 a plurality of fused ring-shaped self-assembled, scaffold-free, high-density cell aggregates, at least one cell aggregate including a plurality of cells and a plurality of biocompatible and biodegradable nanoparticles and/or microparticles that are incorporated within the cell aggregates, the nanoparticles and/or microparticles acting as a bulking agent within the cell aggregate to increase the cell aggregate size and/or thickness and improve the mechanical properties of the cell aggregate.   
     
     
         30 . The engineered trachea implant of  claim 29 , wherein the ring-shaped self-assembled, scaffold-free, high-density cell aggregates comprise differing aggregate materials, at least one of the ring-shaped self-assembled, scaffold-free, high-density cell aggregates being provided or formed with or without nanoparticles and/or microparticles and having different properties than the other aggregates to vary the properties of the tube for particular tissue engineering application. 
     
     
         31 . The engineered trachea implant of  claim 29 , wherein the at least one of the fused ring-shaped self-assembled, scaffold-free, high-density cell aggregates comprises a plurality of chondrogenic cells that have been differentiated to form engineered cartilage. 
     
     
         32 . The engineered trachea implant of  claim 29 , comprising alternating first engineered ring-shaped self-assembled, scaffold-free, high-density cell aggregates and second engineered ring-shaped self-assembled, scaffold-free, high-density cell aggregates fused to form a heterogenous modular tissue tube. 
     
     
         33 . The engineered trachea implant of  claim 29 , wherein the first engineered ring-shaped self-assembled, scaffold-free, high-density cell aggregates define cartilaginous portions within the tube and the second engineered ring-shaped self-assembled, scaffold-free, high-density cell aggregates define noncartilaginous portions within the tube. 
     
     
         34 . The engineered trachea implant of  claim 29 , the nanoparticles and/or microparticles comprising a biocompatible and biodegradable polymer. 
     
     
         35 . The engineered trachea implant of  claim 29 , the nanoparticles and/or microparticles including at least one bioactive agent that is differentially and/or controllably released by the nanoparticles and/or microparticles. 
     
     
         36 . The engineered trachea implant of  claim 29 , bioactive agent including at least one of TGF-β1 and/or BMP-2. 
     
     
         37 . The engineered trachea implant of  claim 29 , wherein an inner lumen of the implant includes a mucosal epithelial lining.