Abstract: A simple, highly flexible and scalable platform for making functional complex tissues with heterogeneity and irregularity is provided. The method includes combining undifferentiated cells, such as pluripotent or multipotent stem cells, with a biomaterial to make multiple undifferentiated or naïve subunits, exposing the undifferentiated or naïve subunits to different cell culture environments for induction of differentiation towards different lineages as required by that complex tissue, and combining the then functional subunits with or without the undifferentiated subunits. The differentiated subunits thus combined can be cultured under biological, chemical, and/or physical culture conditions suitable to fine-tune the structural and functional properties of the bioengineered complex tissue to form a bioengineered tissue graft that mimics the structural and functional characteristics of native complex tissue. The bioengineered tissue graft can then used to replace dysfunctional tissue.

Abstract: A simple, highly flexible and scalable platform for making functional complex tissues with heterogeneity and irregularity is provided. The method includes combining undifferentiated cells, such as pluripotent or multipotent stem cells, with a biomaterial to make multiple undifferentiated or naïve subunits, exposing the undifferentiated or naïve subunits to different cell culture environments for induction of differentiation towards different lineages as required by that complex tissue, and combining the then functional subunits with or without the undifferentiated subunits. The differentiated subunits thus combined can be cultured under biological, chemical, and/or physical culture conditions suitable to fine-tune the structural and functional properties of the bioengineered complex tissue to form a bioengineered tissue graft that mimics the structural and functional characteristics of native complex tissue. The bioengineered tissue graft can then used to replace dysfunctional tissue.