Engineering of biomimetic tissue implants with human induced pluripotent stem cells (hiPSCs) holds promise for repairing volumetric tissue loss. However, these implants face challenges in regenerative capability, survival, and geometric scalability at large-scale injury sites.Here, we present scalable Vessel-integrated Muscle-like Lattices (V.M.Ls) containing dense and aligned hiPSC-derived myofibers alongside passively perfusable vessel-like microchannels inside an endomysium-like supporting matrix using an embedded multi-material bioprintingtechnology. The contractile and millimeter-long myofibers are achieved in mechanically-tailored and nanofibrous extracellular matrix-based hydrogels.Incorporating vessel-like latticeenhances myofiber maturation in-vitroand guides host vessel invasion in-vivo, improving implant integration.Consequently, we demonstrate successful de novo muscle formation and muscle function restoration through a combinatorial effect between improved graft-host integration and its increased release of paracrine factors within volumetric muscle loss injury models. The proposed modular bioprinting technology enables scaling up to centimeter-sized pre-vascularized hiPSC-derived muscle tissues with custom geometries for next-generation muscle regenerative therapies.

more >> https://doi.org/10.1016/j.tibtech.2024.08.001