University of Pittsburgh

The United States of America, as Represented by the Secretary, Department of Health and Human Services

Thomas Jefferson University

The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc.

USA as Represented by Secretary of the Navy

US Government as Represented by the Secretary of the Army

Johns Hopkins University

University System of Maryland

Ri.med Foundation

Fondazione Ri.med

Rocky Sung Chi Tuan

Riccardo Lucca Gottardi

Hang Lin

Peter Alexander

Douglas A Nelson, Jr

Robert E Akins, Jr

Thomas P Lozito

Wesley M Jackson

Leon J Nesti

Jennifer H Elisseeff

Dongan Wang

Qiang Li

Benjamin Burke Rothrauff

Michael Seth Gold

Shinsuke Kihara

Brian D Mariani

Davide Marino

Sheldon S Lin

Yuanheng Yang

Wan-Ju Li

Ronald Paul Silverman

Steven D Hudson

Juan M Taboas

Yangzi Jiang

Bryan Romell

Benajmin Burke Rothrauff

Riccardo Luca Gottardi

Disclosed herein are various bioreactor devices that mimic the mammalian joint. The bioreactor device can include a series of bioreactor chambers that contain different components of the joint, such as bone, cartilage, synovium, nerve and ligament. At least two different nutrient fluid circulation systems connect subsets of the bioreactor chambers to differentially supply nutrient fluids at concentrations optimized for the tissue that the fluid nourishes. For example, relatively hypoxic fluid can be supplied to synovium and cartilage to mimic oxygenation in the joint compartment, but normoxic fluid can be supplied to the bone and other components that have an arterial supply that provides higher oxygen concentrations. One or more or all of the bioreactor chambers can be supplied with separate inlets through which perturbation agents (such as drugs or other agents) can be introduced to model the effect of the perturbations on different components of the system. In some cases, the system can include a well plate having a plurality of wells and a bioreactor situated in each well of the well plate.

Organ chip to model mammalian joint

Disclosed herein are various bioreactor devices and systems for growing cellular material, and related methods of growing cellular material. In some cases, a system can include a well plate having a plurality of wells and a bioreactor situated in each well of the well plate. In some cases, a bioreactor can include an inner body which divides the bioreactor into several distinct chambers and facilitates the growth of a multi-tissue sample in the bioreactor. In some cases, a system can include a mechanical actuator situated to mechanically stress tissues grown in a bioreactor.

Modular, microfluidic, mechanically active bioreactor for 3D, multi-tissue, tissue culture

Disclosed mechanical stimulator systems can maintain the sterility of biological samples within a multi-well plate while mechanically stimulating the samples. The systems disclosed herein allow for the individual activation by mechanical compression of a high number of samples at the same time, while maintaining sterility of the samples. The well plates, guides, actuators, pistons, and other components of the disclosed systems can be configured to be contained in or adjacent to an incubator that can control properties such as gas levels and temperature while at the same time allowing for the mechanical actuation of the biological samples.

Multi-well mechanical stimulation systems and incubators

Provided herein is a ligament ECM soluble fraction useful for the growth and regrowth of ligament tissue. Methods of preparation of the soluble fractions and use of the soluble fractions in growth or regrowth of ligament tissue also are provided.

Extracts for the regeneration of ligaments

A method is provided for producing a live cartilaginous material useful for implantation into a patient. A method of treating a patient comprising implanting a cartilaginous material prepared according to the provided method in an anatomical site in a patient also is provided.

Cartilage material having minimal hypertrophy and robust integration capacity, and uses therefor

Disclosed herein are various bioreactor devices and systems for growing cellular material, and related methods of growing cellular material. In some cases, a system can include a bioreactor system having one or more wells with at least one fluidic passageway coupled to each well to feed fluids to biological material being developed inside the well. In some cases, a bioreactor system can include a main body comprising the perimeter of the well and the fluidic passageways, a cover that forms the top of the well and provides optical access into the well, and a base that forms the bottom surface of the well. The cover and base can be attached and detached from the main body to seal the well closed and to physically access the contents of the well.

Microfluidic tissue development systems

Disclosed herein are Nsp-IL10 polypeptides comprising an Nsp polypeptide and an IL10 polypeptide. In some embodiments, Nsp-IL10 polypeptide is capable of activating an NGF signaling pathway, an IL10 signaling pathway, or both. Also disclosed are methods for treating a disease comprising administering an Nsp-IL10 polypeptide. The methods include treating diseases associated with joint inflammation, such as osteoarthritis.

Nsp-interleukin-10 proteins and uses thereof

Methods are disclosed for forming bone and/or cartilage in an avian subject. The methods include administering to the avian subject a therapeutically effective amount of a composition comprising avian mesenchymal stem cells and a hydrogel that supports the differentiation of the avian mesenchymal stem cells into cells of an osteogenic and/or condrogenic lineage. In some embodiments, methods are disclosed for repairing a bone defect and preventing infection, such as that associated bone fracture, in an avian subject. The methods include administering locally to the bone defect a composition comprising a therapeutically effective amount of avian mesenchymal stem cells and a hydrogel, such as a methacrylated gelatin hydrogel.

Stem cell-based technologies for avian skeletal tissue engineering and regeneration

A graft containing a scaffold that includes a matrix in which are positioned mesenchymal progenitor cells (MPCs) has the capacity to substantially improve wound healing, including wounds resulting from injury to nerve, bone and vascular tissue. MPCs can be harvested from debrided muscle tissue following orthopaedic trauma. The traumatized muscle-derived progenitor cells are a readily available autologous cell source that can be utilized to effect or improve wound healing in a variety of therapeutic settings and vehicles.

Regenerative tissue grafts and methods of making same

A bioreactor device, and a method and system for fabricating tissues and growing cells and tissues in the bioreactor device, accommodates less than about 1 mL (or less than about 200 &#x3bc;L) of local medium volume but sample sizes of about 100 &#x3bc;L or greater. The bioreactor device includes a bioreactor chamber for containing a sample, where sample growth in response to mechanical, electrical, and biofactor stimulation is monitored through one or more optical ports. Embedded sensors are provided for measuring fluid pressure, pH, temperature, and oxygen tension. The bioreactor device can receive different types of mechanical loadings, including fluid shear, hydrostatic pressure, matrix compression, and clinorotation.

Bioreactor device, and method and system for fabricating tissues in the bioreactor device

Functionalized chondroitin sulfate, cross-linked polymer matrices comprising functionalized chondroitin sulfate, and methods of making and using the same are provided. Such polymer matrices may be used for tissue engineering, reconstructing cartilage, and the like. Kits are also provided for detection of cartilage degrading enzymes.

Cross-linked polymer matrices, and methods of making and using same

Tissue graft with non-aligned fiber matrix retains mesenchymal progenitor cells on the non-injury-facing side

Growing community of inventors

Pittsburgh, PA, United States of America

Rocky Sung Chi Tuan