In situ cell delivery using reconstituted photopolymerized chondroitin sulfate glycosaminoglycan hydrogel matrices

Abstract

Disclosed herein are compositions and methods for cellular reconstitution of photopolymerized, lyophilized, bioactive chondroitin sulfate glycosaminoglycan (CS-GAG)-based hydrogel matrices.

1 .- 25 . (canceled) 
     
     
         26 . A microfluidic assay device for evaluating cell preference between a first hydrogel and a second hydrogel, the device comprising:
 a first microfluidic channel configured to receive cells;   a second microfluidic channel in fluid communication with the first microfluidic channel along a first interface and configured to receive a first hydrogel;   a third microfluidic channel in fluid communication with the first microfluidic channel along a second interface and configured to receive a second hydrogel; and   a plurality of barriers arranged along the first interface and the second interface configured to hold the first hydrogel and second hydrogel in their respective microfluidic channels while allowing selective cell migration across the first and second interfaces.   
     
     
         27 . The device according to  claim 26 , wherein the second microfluidic channel comprises the first hydrogel, the third microfluidic channel comprises the second hydrogel, or both. 
     
     
         28 . The device according to  claim 27 , wherein the first hydrogel has a different composition than the second hydrogel. 
     
     
         29 . The device according to  claim 28 , wherein the first hydrogel and the second hydrogel are selected to evaluate cell preference between the first hydrogel and the second hydrogel. 
     
     
         30 . The device according to  claim 27 , wherein the first hydrogel has the same composition as the second hydrogel. 
     
     
         31 . The device according to  claim 27 , wherein the first hydrogel, the second hydrogel, or both are photopolymerized. 
     
     
         32 . The device according to  claim 27 , wherein the first hydrogel, the second hydrogel, or both comprise chondroitin sulfate glycosaminoglycan (CS-GAG). 
     
     
         33 . The device according to  claim 27 , wherein the first hydrogel is selected from one or more of agarose (AG), hyaluronic acid (HA), monosulfated chondroitin-4-sulfate (CS-A), chondroitin-6-sulfate (CS-C), or disulfated chondroitin-4,6-sulfate (CS-E). 
     
     
         34 . The device according to  claim 27 , wherein the second hydrogel is selected from one or more of agarose (AG), hyaluronic acid (HA), monosulfated chondroitin-4-sulfate (CS-A), chondroitin-6-sulfate (CS-C), or disulfated chondroitin-4,6-sulfate (CS-E). 
     
     
         35 . The device according to  claim 27 , wherein the first hydrogel, the second hydrogel, or both comprise one or more of a trophic factor, an adhesion molecule, an adhesion molecule receptor, or a combination thereof. 
     
     
         36 . The device according to  claim 35 , wherein the trophic factor comprises CXCL12. 
     
     
         37 . The device according to  claim 26 , wherein at least one of the first microfluidic channel, the second microfluidic channel, the third microfluidic channel, or the plurality of barriers comprises poly-di-methyl-siloxane (PDMS). 
     
     
         38 . The device according to  claim 26 , wherein each of the plurality of barriers has a trapezoidal shape. 
     
     
         39 . The device according to  claim 26 , wherein each of the plurality of barriers has a largest dimension of about 100 micrometers and is spaced about 50 micrometers from a nearest other barrier of the plurality of barriers. 
     
     
         40 . The device according to  claim 26 , wherein each of the plurality of barriers has a largest dimension of about 300 micrometers and is spaced about 100 micrometers from a nearest other barrier of the plurality of barriers. 
     
     
         41 . The device according to  claim 26 , wherein the first microfluidic channel is located between the second microfluidic channel and the third microfluidic channel. 
     
     
         42 . The device according to  claim 26 , wherein at least one of the first, second, or third microfluidic channels is in fluid communication with one or more wells each having a diameter of 4 or 5 millimeters. 
     
     
         43 . The device according to  claim 26 , wherein at least one of the first, second, or third microfluidic channels has a length of 10 millimeters. 
     
     
         44 . The device according to  claim 26 , wherein at least one of the first, second, or third microfluidic channels has a width of 1000 micrometers. 
     
     
         45 . The device according to  claim 26 , wherein the device is coated with poly-D-lysine. 
     
     
         46 . The device according to  claim 26 , wherein the device is sterilized. 
     
     
         47 . A method of evaluating cell preference between a first hydrogel and a second hydrogel, the method comprising:
 placing a cell suspension in the first microfluidic channel of the device of  claim 27 ;   incubating to allow cell migration; and   quantifying cell migration into each of the first hydrogel and the second hydrogel.