Abstract: Systems and methods are disclosed herein for use in transducing, activating, and otherwise treating cells. Cells are introduced into an inner layer of a multi-layered stack that defines at least one flow chamber and a plurality of cell entrainment regions. Vertical flow through the stack entrains the cells in the cell entrainment regions along with genetic information introduction agents or other additives, before the cells are washed using a reverse vertical flow and are collected from the device.

Abstract: The present disclosure provides compositions and methods for treating an auditory disease in a subject in need thereof comprising administering an effective amount of a gel-based precursor that includes an inner ear-specific therapeutic compound directly into the cochlea of the subject.

Abstract: A microfluidic device is provided. The microfluidic device includes a first transparent, solid support layer. A first polymeric layer defining at least one chamber is attached to the first transparent, solid support layer. A semi-permeable membrane is attached to the first polymeric layer. A second polymeric layer is attached to the opposite side of the semi-permeable membrane from the first polymeric layer. The second polymeric layer has a thickness of less than 300 microns and defines at least one chamber positioned to overlap with at least one chamber in the first polymeric layer. A first manifold structure is attached to an input end of at least one chamber and a second manifold structure is attached to an output end of at least one chamber.

Abstract: Systems and methods are disclosed herein for use in transducing, activating, and otherwise treating cells. Cells are introduced into an inner layer of a multi-layered stack that defines at least one flow chamber and a plurality of cell entrainment regions. Vertical flow through the stack entrains the cells in the cell entrainment regions along with genetic information introduction agents or other additives, before the cells are washed using a reverse vertical flow and are collected from the device.

Abstract: Methods and materials for making complex, living, vascularized tissues for organ and tissue replacement, especially complex and/or thick, structures, such as liver tissue is provided. Tissue lamina is made in a system comprising an apparatus having (a) a first mold or polymer scaffold, a semi-permeable membrane, and a second mold or polymer scaffold, wherein the semi-permeable membrane is disposed between the first and second molds or polymer scaffolds, wherein the first and second molds or polymer scaffolds have means defining microchannels positioned toward the semi-permeable membrane, wherein the first and second molds or polymer scaffolds are fastened together; and (b) animal cells. Methods for producing complex, three-dimensional tissues or organs from tissue lamina are also provided.

Abstract: A microfluidic device is provided. A manifold having a first channel, a second channel, and a third channel configured to transport blood can be coupled to a substrate defining an artificial vasculature. The first channel can be configured to carry blood in a first direction. Each of the second and third channels can couple to the first channel at a first junction and can be configured to receive blood from the first channel. The second channel can be configured to carry blood in a second direction away from the first direction. The third channel can be configured to carry blood in a third direction away from the second direction. The first, second, and third channels can be non-coplanar.

Abstract: The systems and methods disclosed herein are generally related to a cell culture system. More particularly, the systems and methods enable the culturing and interconnecting of a plurality of tissue types in a biomimetic environment. By culturing organ specific tissue types within a biomimetic environment and interconnecting each of the organ systems in a physiologically meaningful way, experiments can be conducted on in vitro cells that substantially mimic the responses of in vivo cell populations. In some implementations, the organ systems are fluidically connected with a constant-volume pump.

Abstract: An implantable drug delivery apparatus for delivering a drug into a bodily fluid in a bodily cavity of a patient over a period of time includes a drug supply reservoir to supply drug into a delivery channel and an actuator for delivering the drug to a predetermined location in the bodily cavity of the patient, such as, for example, a cochlea of a human ear. The drug is loaded into the delivery channel while producing substantially negligible flow at an outlet of the delivery channel.

Abstract: An compact hydraulic manifold for transporting shear sensitive fluids is provided. A channel network can include a trunk and branch architecture coupled to a bifurcation architecture. Features such as tapered channel walls, curvatures and angles of channels, and zones of low fluid pressure can be used to reduce the size while maintaining wall shear rates within a narrow range. A hydraulic manifold can be coupled to a series of microfluidic layers to construct a compact microfluidic device.

Abstract: The present invention provides an in vitro blood vessel model for investigation of drug induced vascular injury and other vascular pathologies. The in vitro blood vessel model provides two channels separated by a porous membrane that is coated on one side by an endothelial cell layer and is coated on the other side by a smooth muscle cell layer, wherein said model is susceptible to the extravasation of red blood cells across said porous membrane due to drug induced vascular injury.

Abstract: Methods and materials for making complex, living, vascularized tissues for organ and tissue replacement, especially complex and/or thick, structures, such as liver tissue is provided. Tissue lamina is made in a system comprising an apparatus having (a) a first mold or polymer scaffold, a semi-permeable membrane, and a second mold or polymer scaffold, wherein the semi-permeable membrane is disposed between the first and second molds or polymer scaffolds, wherein the first and second molds or polymer scaffolds have means defining microchannels positioned toward the semi-permeable membrane, wherein the first and second molds or polymer scaffolds are fastened together; and (b) animal cells. Methods for producing complex, three-dimensional tissues or organs from tissue lamina are also provided.

Abstract: The present disclosure describes a blood oxygenator that includes a checkerboard layout of fluid (e.g., blood) and gas (e.g., oxygen) channels. When viewed as a cross-section through each of the channels of the oxygenator, the checkerboard configuration includes alternating gas and fluid channels in both the x-axis (e.g., in-plane) and in the y-axis (e.g., out-of-plane) directions. The oxygenator described herein reduces manufacturing complexity by using first, second, and third polymer layers that include asymmetrical channel designs. The channel designs include “open” gas channels, which are exposed to the ambient atmosphere. The oxygenator is placed within a pressure vessel to drive gas into each of the open gas channels, which in some implementations, negates the need for a gas manifold.

Abstract: An compact hydraulic manifold for transporting shear sensitive fluids is provided. A channel network can include a trunk and branch architecture coupled to a bifurcation architecture. Features such as tapered channel walls, curvatures and angles of channels, and zones of low fluid pressure can be used to reduce the size while maintaining wall shear rates within a narrow range. A hydraulic manifold can be coupled to a series of microfluidic layers to construct a compact microfluidic device.

Abstract: Disclosed herein are systems and devices for culturing cells in a biomimetic environment of a cellularized nephron unit, and methods for fabricating and using the cellularized nephron unit.

Abstract: The systems and methods disclosed herein are generally related to a cell culture system. More particularly, the systems and methods enable the culturing and interconnecting of a plurality of tissue types in a biomimetic environment. By culturing organ specific tissue types within a biomimetic environment and interconnecting each of the organ systems in a physiologically meaningful way, experiments can be conducted on in vitro cells that substantially mimic the responses of in vivo cell populations. In some implementations, the system is used to monitor how organ systems respond to agents such as toxins or medications. The system enables the precise and controlled delivery of these agents, which, in some implementations, enables the biomimetic dosing of drugs in humans to be mimicked.

Abstract: The general disclosure discusses a system and method for improving the efficacy of blood filtration treatments such as hemodialysis, hemofiltration, and hemodiafiltration. More particularly, the disclosure discusses a microfluidic device that includes first and second channels separated by a permeable membrane. One of the channels is configured for blood flow and includes a protein gel disruption layer. The protein gel disruption layer includes a plurality of elements at least partially extending across the blood flow channel that reduce the formation of a boundary layer or gel layer at the blood-membrane interface.

Abstract: The present invention provides an in vitro blood vessel model for investigation of drug induced vascular injury and other vascular pathologies. The in vitro blood vessel model provides two channels separated by a porous membrane that is coated on one side by an endothelial cell layer and is coated on the other side by a smooth muscle cell layer, wherein said model is susceptible to the extravasation of red blood cells across said porous membrane due to drug induced vascular injury.

Abstract: The systems and methods disclosed herein are generally related to a cell culture system. More particularly, the systems and methods enable the culturing and interconnecting of a plurality of tissue types in a biomimetic environment. By culturing organ specific tissue types within a biomimetic environment and interconnecting each of the organ systems in a physiologically meaningful way, experiments can be conducted on in vitro cells that substantially mimic the responses of in vivo cell populations. In some implementations, the system is used to monitor how organ systems respond to agents such as toxins or medications. The system enables the precise and controlled delivery of these agents, which, in some implementations, enables the biomimetic dosing of drugs in humans to be mimicked.

Abstract: The invention provides method of fabricating a scaffold comprising a fluidic network, including the steps of: (a) generating an initial vascular layer for enclosing the chamber and providing fluid to the cells, the initial vascular layer having a network of channels for fluid; (b) translating the initial vascular layer into a model for fluid dynamics analysis; (c) analyzing the initial vascular layer based on desired parameters selected from the group consisting of a characteristic of a specific fluid, an input pressure, an output pressure, an overall flow rate and combinations thereof to determine sheer stress and velocity within the network of channels; (d) measuring the sheer stress and the velocity and comparing the obtained values to predetermined values; (e) determining if either of the shear stress or the velocity are greater than or less than the predetermined values, and (f) optionally modifying the initial vascular layer and repeating steps (b)-(e).

Abstract: The invention provides systems and methods for exchanging gas in an oxygenator device, and methods for preparing and using such oxygenator devices. The systems and methods can be used to transfer oxygen to blood to assist lung function in a patient.