Person:

Homan, Kimberly

Three-dimensional models of kidney tissue that recapitulate human responses are needed for drug screening, disease modeling, and, ultimately, kidney organ engineering. Here, we report a bioprinting method for creating 3D human renal proximal tubules in vitro that are fully embedded within an extracellular matrix and housed in perfusable tissue chips, allowing them to be maintained for greater than two months. Their convoluted tubular architecture is circumscribed by proximal tubule epithelial cells and actively perfused through the open lumen. These engineered 3D proximal tubules on chip exhibit significantly enhanced epithelial morphology and functional properties relative to the same cells grown on 2D controls with or without perfusion. Upon introducing the nephrotoxin, Cyclosporine A, the epithelial barrier is disrupted in a dose-dependent manner. Our bioprinting method provides a new route for programmably fabricating advanced human kidney tissue models on demand.

A new bioprinting method is reported for fabricating 3D tissue constructs replete with vasculature, multiple types of cells, and extracellular matrix. These intricate, heterogeneous structures are created by precisely co-printing multiple materials, known as bioinks, in three dimensions. These 3D micro-engineered environments open new ­avenues for drug screening and fundamental studies of wound healing, angiogenesis, and stem-cell niches.

Myelination is critical for transduction of neuronal signals, neuron survival and normal function of the nervous system. Myelin disorders account for many debilitating neurological diseases such as multiple sclerosis and leukodystrophies. The lack of experimental models and tools to observe and manipulate this process in vitro has constrained progress in understanding and promoting myelination, and ultimately developing effective remyelination therapies. To address this problem, we developed synthetic mimics of neuronal axons, representing key geometric, mechanical, and surface chemistry components of biological axons. These artificial axons exhibit low mechanical stiffness approaching that of a human axon, over unsupported spans that facilitate engagement and wrapping by glial cells, to enable study of myelination in environments reflecting mechanical cues that neurons present in vivo. Our 3D printing approach provides the capacity to vary independently the complex features of the artificial axons that can reflect specific states of development, disease, or injury. Here, we demonstrate that oligodendrocytes’ production and wrapping of myelin depend on artificial axon stiffness, diameter, and ligand coating. This biofidelic platform provides direct visualization and quantification of myelin formation and myelinating cells’ response to both physical cues and pharmacological agents.