Bioreactor

Abstract

A bioreactor comprising a housing defining a perfusion chamber, the housing including at least one port, wherein the at least one port is coupled to the housing, and a sample holder positioned within the perfusion chamber. A bioreactor and spheroid-based biofabrication method for making perfusible tissue constructs and perfusing them.

What is claimed is: 
     
         1 . A bioreactor comprising
 a housing configured to define a perfusion chamber; and   a sample holder positioned within the perfusion chamber, the sample holder including a base and a platen configured to be positioned in abutment with the base, wherein at least one of the base and the platen includes at least one handling extension;   wherein the housing further includes a cover configured to couple with the housing to regulate interaction between the perfusion chamber and the atmosphere, and at least one observation port configured to be an analyzing portion within the cover designed with acoustic properties which facilitate transmission and reception of a plurality of ultrasound signals configured for image formation and ultrasound-based fluid flow measurements to provide an aseptic management of the transmission and reception.   
     
     
         2 . The bioreactor of  claim 1 , wherein the base includes at least one securing extension configured to hold the platen in abutment with the base. 
     
     
         3 . The bioreactor of  claim 2 , wherein the at least one securing extension includes two separate securing extensions. 
     
     
         4 . The bioreactor of  claim 1 , wherein the sample holder further includes at least one perfusion opening extending through the base and the platen. 
     
     
         5 . The bioreactor of  claim 1 , wherein the platen further includes a skirt extending from a bottom surface of the platen. 
     
     
         6 . The bioreactor of  claim 4 , wherein the at least one handling extension includes two handling extension, each of the two handling extensions being positioned to adjacent a side of the at least one perfusion opening. 
     
     
         7 . The bioreactor of  claim 1 , wherein the plurality of ultrasound signals includes biological and material properties. 
     
     
         8 . A method for preparing a biologically active tissue construct made from cells and extracellular matrix comprising:
 partially or fully filling a bioreactor with a biocompatible fluid, the bioreactor including a housing defining a perfusion chamber, and a sample holder positioned within the perfusion chamber, wherein the housing includes an inlet port and an outlet port, the inlet port and the outlet port being integrally formed as a single one-piece structure with the housing;   placing the tissue construct into or onto a module associated with the sample holder; and   at least one of: coupling the inlet port and the outlet port of the bioreactor to a perfusion pump, placing the bioreactor in an incubator, and manipulating the tissue construct within the bioreactor to apply at least one of nutritious perfusion and stimuli.   
     
     
         9 . The method of  claim 8  further comprising observing the tissue construct through at least one observation port within the housing. 
     
     
         10 . The method of  claim 9  further comprising transferring the bioreactor to a desired area. 
     
     
         11 . The method of  claim 8  further comprising including in the model, a base and a platen configured to be positioned in abutment with the base. 
     
     
         12 . The method of  claim 9 , further comprising including in the housing, a cover and an analyzing portion of the cover. 
     
     
         13 . The method of  claim 8 , further comprising including the at least one observation port being positioned along a wall of the housing. 
     
     
         14 . The method of  claim 8 , further comprising simultaneously performing observing the tissue construct and printing the tissue construct. 
     
     
         15 . The method of  claim 8 , further comprising generating the tissue construct such that the tissue construct is self-supporting and having one or more perfusion channels. 
     
     
         16 . The method of  claim 15 , further comprising creating the one or more perfusion channels of the tissue construct using corresponding one or more needles of the platen. 
     
     
         17 . A perfusible tissue construct capable of supporting the stress of its own weight when unsupported by any other structure or medium other than its own bulk or air, the perfusible tissue construct comprising:
 a body removably attached to a platen configured to be positioned in abutment with a base of a sample holder disposed within a perfusion chamber, which contains a biocompatible fluid sufficient to maintain tissue viability, such that the tissue construct remains in alignment with a plurality of perfusion channels disposed in the tissue construct independent of an intervening non-tissue material penetrating through the tissue construct,   wherein the platen and the base include at least one perfusion opening configured to align with at least one of the plurality of perfusion channels such that the fluid is perfused through the base, the platen, and the tissue construct.   
     
     
         18 . The perfusible tissue construct of  claim 17 , wherein at least one of the base and the platen includes a plurality of perfusion openings, each of a majority of the plurality of perfusion openings configured to align with at least one of the plurality of channels disposed in the tissue construct. 
     
     
         19 . The perfusible tissue construct of  claim 17 , wherein the sample holder includes a construct support configured to removably attach the body of the tissue to the platen. 
     
     
         20 . The perfusible tissue construct of  claim 19 , wherein the construct support includes an adhesive interface. 
     
     
         21 . The perfusible tissue construct of  claim 17 , wherein the tissue construct is capable of supporting its own weight without the support of any intervening mechanical support.