Abstract: The present invention relates to systems, compositions, and methods for multi-cellular bioprinting of vascularized tissue constructs comprising hierarchical vascular networks. The method employs a dual-bioink strategy involving a fibrous microgel matrix bioink with tunable stiffness, self-healing rheology, and microporosity to support capillary self-assembly, and a sacrificial bioink that defines perfusable macro-channels upon removal. The system integrates top-down printing with bottom-up cellular self-organization within a programmable bioprinting platform. A key inventive aspect lies in engineering the physical topography of the matrix to actively guide vascular morphogenesis, moving beyond conventional permissive scaffolds. The integrated platform enables the fabrication of complex, biomimetic vascular networks with enhanced mass transport, cell viability, and in vivo integration potential.

Abstract: It has been discovered that reducing, inhibiting or preventing the expression of immunosuppressive cytokines or tolergenic agents in antigen presenting cells improves the ability of the antigen presenting cell to promote an immune response. One embodiment provides a genetically engineered antigen presenting cell that has reduced or no expression of IL-10. Preferred antigen presenting cells are dendritic cells. Expression of IL-10 can be inhibited or blocked by genetically engineering the antigen presenting cell to express inhibitory nucleic acids that inhibit or prevent the expression mRNA encoding immunosuppressive cytokines. Inhibitory nucleic acids include siRNA, antisense RNA, antisense DNA, microRNA, and enzymatic nucleic acids that target mRNA encoding immunosuppressive cytokines. Immunosuppressive cytokines include, but are not limited to IL-10, TGF-?, IL-27, IL-35, or combinations thereof. Tolerogenic agents include but are not limited to indoleamine 2,3-dioxygenase.