Children suffering from microtia have few options for auricular reconstruction. Tissue engineering approaches attempt to replicate the complex anatomy and structure of the ear with autologous cartilage but have been limited by access to clinically accessible cell sources. Here we present a full-scale, patient-based human ear generated by implantation of human auricular chondrocytes and human mesenchymal stem cells in a 1:1 ratio. Additional disc construct surrogates were generated with 1:0, 1:1, and 0:1 combinations of auricular chondrocytes and mesenchymal stem cells. After 3 months in vivo, monocellular auricular chondrocyte discs and 1:1 disc and ear constructs displayed bundled collagen fibers in a perichondrial layer, rich proteoglycan deposition, and elastin fiber network formation similar to native human auricular cartilage, with the protein composition and mechanical stiffness of native tissue. Full ear constructs with a 1:1 cell combination maintained gross ear structure and developed a cartilaginous appearance following implantation. These studies demonstrate the successful engineering of a patient-specific human auricle using exclusively human cell sources without extensive in vitro tissue culture prior to implantation, a critical step towards the clinical application of tissue engineering for auricular reconstruction.

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We have successfully demonstrated an innovative cell sourcing strategy that facilitates our efforts to achieve clinical translation of our high fidelity, patient-specific ears for auricular reconstruction utilizing only half of the requisite auricular chondrocytes to fabricate mature elastic cartilage.

Variability is observed at multiple-scales in the brain and ubiquitous in perception. However, the nature of perceptual variability is an open question. We focus on variability during perceptual rivalry, a form of neuronal competition. Rivalry provides a window into neural processing since activity in many brain areas is correlated to the alternating perception rather than a constant ambiguous stimulus. It exhibits robust properties at multiple scales including conscious awareness and neuron dynamics. The prevalent theory for spiking variability is called the balanced state; whereas, the source of perceptual variability is unknown. Here we show that a single biophysical circuit model, satisfying certain mutual inhibition architectures, can explain spiking and perceptual variability during rivalry. These models adhere to a broad set of strict experimental constraints at multiple scales. As we show, the models predict how spiking and perceptual variability changes with stimulus conditions.