Plant-derived nanofibrillar cellulose hydrogel for cell culture and chemical testing

Abstract

The present invention relates a method for chemical testing, comprising culturing cells in a first plant-derived nanofibrillar cellulose (NFC)hydrogel to obtain in vivo like cells; exposing the in vivo like cells to a test chemical; optionally within another plant-derived NFC hydrogel; incubating the exposed in vivo like cells; detecting during or after incubating, the impact of the test chemical on the in vivo like cells by at least one detection; and removing the plant-derived NFC hydrogel at least once at any stage after obtaining the in vivo like cells and before at least one detection used for detecting the impact of the test chemical on the in vivo like cells. The invention further relates to the use of plant-derived NFC hydrogel in a method for chemical testing, the use of in vivo like cells obtained by culturing cells in plant-derived NFC hydrogel for chemical testing and to a kit for chemical testing comprising plant-derived NFC hydrogel, instructions and a cell or test chemical library.

1 - 20 . (canceled) 
     
     
         21 . A method for culturing in vivo like cells, the method comprising:
 a) culturing cells on or in a first plant-derived nanofibrillar cellulose (NFC) hydrogel to obtain in vivo like cells; and   b) exposing the in vivo like cells to a second plant-derived NFC hydrogel, the second NFC hydrogel having at least one property different than the first NFC hydrogel, the at least one property including stiffness, concentration, shear-zero viscosity, NFC hydrogel charge, transparency, size distribution, length, diameter, chemical composition, or rheological properties.   
     
     
         22 . The method of  claim 21 , wherein the cells are evenly dispersed on or in at least one of the first or second NFC hydrogel. 
     
     
         23 . The method of  claim 21 , wherein the second NFC hydrogel is a liquid. 
     
     
         24 . The method of  claim 21 , further comprising adjusting the stiffness of at least one of the first or second NFC hydrogel by dilution. 
     
     
         25 . The method of  claim 24 , wherein the stiffness is adjusted with cells cultured within the at least one of the first or second NFC hydrogel. 
     
     
         26 . The method of  claim 21 , wherein at least one of the first or second NFC hydrogel has a consistency of from 0.05 to 10% w/w. 
     
     
         27 . The method of  claim 21 , further comprising sterilizing at least one of the first or second NFC hydrogel prior to culturing the cells thereon. 
     
     
         28 . The method of  claim 21 , wherein the in vivo like cells are exposed to a test chemical. 
     
     
         29 . The method of  claim 28 , further comprising:
 (c) incubating the exposed in vivo like cells exposed to the test chemical; and   (d) detecting, during or after the incubation, a qualitative and/or quantitative impact of the test chemical on the in vivo like cells by at least one detection technique.   
     
     
         30 . The method of  claim 29 , wherein the at least one detection technique is selected from the group consisting of chromatography, spectroscopy, microscopy, photometry, laser or flow-cytometry, high-throughput screening, or any combination thereof. 
     
     
         31 . The method of  claim 21 , wherein at least one of the first or second NFC hydrogel comprises cellulose I. 
     
     
         32 . The method of  claim 21 , wherein at least one of the first or second NFC hydrogel has a zero-shear viscosity and yield stress for sufficiently suspending the in vivo like cells evenly therein and for avoiding sedimentation of the in vivo like cells. 
     
     
         33 . The method of  claim 32 , wherein at least one of the first or second NFC hydrogel generally protects the cultured in vivo like cells from disturbances caused by handling thereof. 
     
     
         34 . The method of  claim 21 , wherein the in vivo like cells are exposed to the second NFC hydrogel after removing at least some of the first NFC hydrogel. 
     
     
         35 . A method for determining the impact of a test chemical on living cells, comprising:
 a) forming a first plant-derived nanofibrillar cellulose (NFC) hydrogel into a three-dimensional structure, the first NFC hydrogel having living cells, the first NFC hydrogel having a first concentration of nanofibrillar cellulose that is in range of 0.1 to 4 w to;   b) exposing the living cells in the first NFC hydrogel to a second plant-derived NFC hydrogel that is formed onto the first NFC hydrogel, the second NFC hydrogel also having living cells and a second concentration of nanofibrillar cellulose that is different than the first concentration;   c) incubating the living cells having the test chemical applied thereto; and   d) detecting, during or after the incubating, a qualitative and/or quantitative impact of the test chemical on the living cells by at least one detection technique.   
     
     
         36 . The method of  claim 35 , wherein said test chemical is selected from the group consisting of drugs, drug candidates, pro-drugs, pro-drug candidates, nanoparticles, cell regulatory agents, food or food additives, household products, industrial chemicals, packing materials, air freshener, plant growth regulatory agents, environmental toxins, pesticides, personal care products, or their chemical ingredients. 
     
     
         37 . The method of to  claim 35 , wherein the at least one detection technique is selected from the group consisting of chromatography, spectroscopy, microscopy, photometry, laser or flow-cytometry, high-throughput screening, or any combination thereof. 
     
     
         38 . A method for determining the impact of a test chemical on living cells, comprising:
 a) forming a first plant-derived nanofibrillar cellulose (NFC) hydrogel into a three-dimensional structure, the first NFC hydrogel having living cells, the first NFC hydrogel having a first concentration of nanofibrillar cellulose that is in range of 0.1 to 4 wt %;   b) exposing the living cells in the first NFC hydrogel to a second plant-derived NFC hydrogel that is formed onto the first NFC hydrogel, the second NFC hydrogel having at least one property different than the first NFC hydrogel, the at least one property including stiffness, concentration, shear-zero viscosity, NFC hydrogel charge, transparency, size distribution, length, diameter, chemical composition, or rheological properties;   c) incubating the living cells having the test chemical applied thereto; and   d) detecting, during or after the incubating, a qualitative and/or quantitative impact of the test chemical on the living cells by at least one detection technique.   
     
     
         39 . The method of  claim 38 , wherein said test chemical is selected from the group consisting of drugs, drug candidates, pro-drugs, pro-drug candidates, nanoparticles, cell regulatory agents, food or food additives, household products, industrial chemicals, packing materials, air freshener, plant growth regulatory agents, environmental toxins, pesticides, personal care products, or their chemical ingredients. 
     
     
         40 . The method of  claim 38 , wherein the at least one detection technique is selected from the group consisting of chromatography, spectroscopy, microscopy, photometry, laser or flow-cytometry, high-throughput screening, or any combination thereof.