Three-dimensional integrated organ printing (IOP) technology seeks to fabricate tissue constructs that can mimic the structural and functional properties of native tissues. This technology is particularly useful for complex tissues such as those in the musculoskeletal system, which possess regional differences in cell types and mechanical properties. Here, we present the use of our IOP system for the processing and deposition of four different components for the fabrication of a single integrated muscle-tendon unit (MTU) construct. Thermoplastic polyurethane (PU) was co-printed with C2C12 cell-laden hydrogel-based bioink for elasticity and muscle development on one side, while poly(ϵ-caprolactone) (PCL) was co-printed with NIH/3T3 cell-laden hydrogel-based bioink for stiffness and tendon development on the other. The final construct was elastic on the PU-C2C12 muscle side (E = 0.39 ± 0.05 MPa), stiff on the PCL-NIH/3T3 tendon side (E = 46.67 ± 2.67 MPa) and intermediate in the interface region (E = 1.03 ± 0.14 MPa). These constructs exhibited >80% cell viability at 1 and 7 d after printing, as well as initial tissue development and differentiation. This study demonstrates the versatility of the IOP system to create integrated tissue constructs with region-specific biological and mechanical characteristics for MTU engineering.

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Progress in understanding kidney disease mechanisms and the development of targeted therapeutics have been limited by the lack of functional in vitro models that can closely recapitulate human physiological responses. Organ Chip (or organ-on-a-chip) microfluidic devices provide unique opportunities to overcome some of these challenges given their ability to model the structure and function of tissues and organs in vitro. Previously established organ chip models typically consist of heterogenous cell populations sourced from multiple donors, limiting their applications in patient-specific disease modeling and personalized medicine. In this study, we engineered a personalized glomerulus chip system reconstituted from human induced pluripotent stem (iPS) cell-derived vascular endothelial cells (ECs) and podocytes from a single patient. Our stem cell-derived kidney glomerulus chip successfully mimics the structure and some essential functions of the glomerular filtration barrier. We further modeled glomerular injury in our tissue chips by administering a clinically relevant dose of the chemotherapy drug Adriamycin. The drug disrupts the structural integrity of the endothelium and the podocyte tissue layers, leading to significant albuminuria as observed in patients with glomerulopathies. We anticipate that the personalized glomerulus chip model established in this report could help advance future studies of kidney disease mechanisms and the discovery of personalized therapies. Given the remarkable ability of human iPS cells to differentiate into almost any cell type, this work also provides a blueprint for the establishment of more personalized organ chip and ‘body-on-a-chip’ models in the future.