Methods of patterning cells on a surface of a substrate and programmed assembly of three-dimensional living tissues

A method of generating a pattern of cells, comprising:

• disposing a two dimensional (2D) pattern of nucleic acids on a surface of a substrate;
• contacting the patterned nucleic acids under hybridization conditions with a first suspension of cells, wherein cells of the first suspension comprise cell surface-attached nucleic acids complementary to the patterned nucleic acids, wherein the hybridization conditions are sufficient for specific hybridization between the cell surface-attached nucleic acids and the patterned nucleic acids and wherein the cell surface-attached nucleic acids hybridize to the patterned nucleic acids to pattern the cells on the surface of the substrate;
• and
• removing the pattern of cells by:
• covering the pattern of cells with a liquid biocompatible matrix comprising a nuclease under conditions that maintain the biocompatible matrix in a liquid state;
• and
• incubating the cells in the biocompatible matrix under physiological temperature to simultaneously trigger setting of the biocompatible matrix around the cells and cleavage of the nucleic acids by the nuclease;
• and
• removing the matrix from the surface, wherein the pattern of cells is retained in the matrix upon removal.