University of Pennsylvania

University of Michigan

Children's Medical Center Corporation

Dongeun Huh

Mark J Mondrinos

Jeongyun Seo

Shuichi Takayama

Cassidy Blundell

Katsuo Kurabayashi

Steven J Skerlos

Dwight E Stambolian

Yi-Chung Tung

Andrei Georgescu

Woo Yul Byun

Sunghee Estelle Park

Wenli Yang

James B Grotberg

Donald Elliot Ingber

Gary Daniel Smith

Michael D Thouless

Brenda S Cho

Xiaoyue Zhu

Kristen L Mills

Nicholas Joseph Douville

Mina Massaro-Giordano

Alex Yoon Yi

Joseph Chang

This present disclosure relates to a bioengineering approach based on microphysiological culture to mimic tissue-tissue interface. Accordingly, the present disclosure provides methods, compositions and kits related to the approach.

Micro-engineered models of the human eye and methods of use

Systems and methods for multilane vasculature and multiorgan vascular-vessel fluidic interfaces in in vitro models. The method includes embedding at least one tissue into a 3D structure, forming a vascular interface for nutrient perfusion into the tissue or tissues, tuning the vascular interface or interfaces together or separately to possess a property of a native biological target tissue or target environment by modifying a vessel attribute; and lining a fluidic interface channel, for providing a growth fluid in a physiologically recapitulating manner. The 3D structure includes a vasculogenic element for angiogenesis or vasculogenesis.

Systems and methods for multilane vasculature

The presently disclosed subject matter provides a biomimetic lung disease model, and methods of its production and use. In one exemplary embodiment, the biomimetic lung disease model can include a first and second microchannel with a membrane coated with airway epithelial cells disposed between the microchannels and at least one device coupled to the biomimetic model that delivers an agent to at least one microchannel. In certain embodiments, the agent is cigarette smoke.

Lung disease models on a chip

The presently disclosed subject matter provides native extracellular matrix-derived membrane inserts for organs-on-chips, multilayer microfluidics microdevices, bioreactors, tissue culture inserts, and two-dimensional and three-dimensional cell culture systems. A microfluidic cell culture is provided that can include at least one membrane including extracellular matrix (ECM) material. The ECM material can be used to construct a perfusable microfluidic system including a plurality of layers of microfabricated cell culture chambers. The microfluidic cell culture can further include a lower layer including a microchannel on which the at least one membrane is placed and an upper layer including another microchannel. The upper layer can be bonded to the lower layer.

Native extracellular matrix-derived membrane inserts for organs-on-chips, multilayer microfluidics microdevices, bioreactors, tissue culture inserts, and two-dimensional and three-dimensional cell culture systems

The presently disclosed subject matter provides a biomimetic organ model, and methods of its production and use. In one exemplary embodiment, the biomimetic organ model can be a multi-layer model including a at least two microchannels and at least one chamber slab with at least one membrane coated with cells disposed between at least one microchannel and the at least one chamber slab. In another exemplary embodiment, the biomimetic organ disease model can be a five-layer model including a first and second microchannel with a membrane-gel layer-membrane coated or encompassing cells disposed between the microchannels. In certain embodiments, at least one device can be coupled to the biomimetic organ model that delivers an agent to at least one microchannel.

Fibrosis model on a chip

The presently disclosed subject matter provides systems and methods for producing a three-dimensional model of a human cervix. A microdevice is provided for culturing human cervical cells. The microdevice can include an upper microchannel including live ectocervical epithelial cells. The microdevice can include a lower microchannel including a first parallel lane and a second parallel lane including stromal media. The first and the second parallel lanes can be lined with live vascular endothelial cells. The lower microchannel can include a third parallel lane including uterine fibroblasts and live smooth muscle cells embedded in hydrogel. The first, second, and third lanes of the lower microchannel can be separated by protrusion structures. The third parallel lane can be positioned in the lower microchannel in between the first and the second parallel lanes. The microdevice can further include a porous membrane positioned in between the upper microchannel and the lower microchannel.

Systems and methods for producing micro-engineered models of the human cervix

A microphysiological platform described herein includes a fluidic synthesizer with a first fluid input selectively coupleable to a source of a first input fluid solution and a second fluid input selectively coupleable to a source of a second input fluid solution. The fluidic synthesizer further includes a fluid output. The microphysiological platform further includes a fluid addressing system with a fluid input fluidically coupled to the fluidic synthesizer fluid output. The fluid addressing system further includes a first fluid output and a second fluid output. The microphysiological platform further includes a first microphysiological device with a fluid input fluidically coupled to the first fluid output of the fluid addressing system and a second microphysiological device with a fluid input fluidically coupled to the second fluid output of the fluid addressing system.

Digital fluid teleportation, advanced biological virtualization, and large scale integration of organ-on-chips and microphysiological models

The presently disclosed subject matter provides a microfluidic device that can simulate capillary blood flow on a fetal side of the device and pooled blood on a maternal side of the device (i.e., intervillous space). The microfluidic device can reconstitute the maternal-fetal interface, can expand the capabilities of cell culture models, and can provide an alternative to current maternal-fetal transfer models.

Artificial placenta and methods of preparation

The presently disclosed subject matter provides an approach to address the needs for microscale control in shaping the spacial geometry and microarchitecture of 3D collagen hydrogels. For example, the disclosed subject matter provides for compositions, methods, and systems employing N-sulfosuccinimidyl-6-(4'-azido-2&#x2032;-nitro-phenylamino)hexanoate ('sulfo-SANPAH'), to prevent detachment of the hydrogel from the anchoring substrate due to cell-mediated contraction.

Systems and methods for immobilizing extracellular matrix material on organ on chip, multilayer microfluidics microdevices, and three-dimensional cell culture systems

The presently disclosed subject provides a biomimetic eye model, and methods of its production and use. In one exemplary embodiment, the biomimetic eye model can include a scaffold having a convex curvature, a fluidic device coupled to the scaffold, a fabricated eyelid coupled to the fluidic device and a motor coupled to the fabricated eyelid. In certain embodiments, the scaffold can be impregnated with one or more keratocytes and a surface of the convex curvature of the scaffold can be covered with one or more layers of epithelial cells.

Growing community of inventors

Villanova, PA, United States of America

Dongeun Huh