Brown University

Etex Corporation

Neurotech S.a.

Valley Forge Scientific Corporation

Fac8cell Pty Limited

Sertoli Technologies, Inc.

Alfred V Vasconcellos

Paul R Sanberg

Patrick Aebischer

Keith E Dionne

Frank T Gentile

Dwaine F Emerich

Michael J Lysaght

Orion D Hegre

Paul E Lacy

Diane Hoffman

Lisa Christenson

David W Scharp

Paul J Mulhauser

Nicholas F Warner

Aliassghar N Tofighi

Moses Goddard

Pramod Chakravarthy

Anne M Rathbun

John G Moldauer

Katherine Jacobs

Jonathan J Rosen

Jerry L Malis

Robert Bartlett Elliott

Craig Reed Halberstadt

Martin T Mortimer

Olga Garkavenko

Ray V Rajotte

Dwaine Emerich

Chris Thanos

Paul Gores

David W Sharp

Richelle Hemendinger

Greg Korbutt

Jannette Dufour

The invention relates to an improved method of culturing hepatocyte cells and non-hepatocyte cells that are capable of secreting liver secretory factors and their use in implantable compositions for treating liver diseases and disorders in patients in need thereof.

Culture and use of cells that secrete liver secretory factors

An immunoisolatory vehicle for the implantation into an individual of cells which produce a needed product or provide a needed metabolic function. The vehicle is comprised of a core region containing isolated cells and materials sufficient to maintain the cells, and a permselective, biocompatible, peripheral region free of the isolated cells, which immunoisolates the core yet provides for the delivery of the secreted product or metabolic function to the individual. The vehicle is particularly well-suited to delivery of insulin from immunoisolated islets of Langerhans, and can also be used advantageously for delivery of high molecular weight products, such as products larger than IgG. A method of making a biocompatible, immunoisolatory implantable vehicle, consisting in a first embodiment of a coextrusion process, and in a second embodiment of a stepwise process. A method for isolating cells within a biocompatible, immunoisolatory implantable vehicle, which protects the isolated cells from attack by the immune system of an individual in whom the vehicle is implanted. A method of providing a needed biological product or metabolic function to an individual, comprising implanting into the individual an immunoisolatory vehicle containing isolated cells which produce the product or provide the metabolic function.

Implantable biocompatible immunoisolatory vehicle for delivery of selected therapeutic products

An immunoisolatory vehicle for the implantation into an individual of cells which produce a needed product or provide a needed metabolic function. The vehicle is comprised of a core region containing isolated cells and materials sufficient to maintain the cells, and a permselective, biocompatible, peripheral region free of the isolated cells, which immunoisolates the core yet provides for the delivery of the secreted product or metabolic function to the individual.

Implantable biocompatible immunoisolatory vehicle for the delivery of selected therapeutic products

Implantable therapy systems are disclosed for the local and controlled delivery of a biologically active factor to the brain, spinal cord and other target regions of a subject suffering from a dibilatating condition. The method of the invention involves surgically exposing an insertion site, generally located above a predetermined treatment site (,), in a patient. A cannula (,), having an obturator (,) or dilator (,) positioned therein, is inserted at the insertion site, defining a pathway to the treatment site. In some instances, the cannula can be inserted along the path of a guidewire (,) previously positioned at the treatment site. The cannula (,) is preferably a low friction polymeric material such as polytetrafluoroethylene. The cannula (,) generally has an open proximal end for receiving the obturator (,) or dilator (,), and an open distal end, preferably a tapered end, for delivery of neurologically active factors to the treatment site (,). The obturator (,) is then removed from the cannula (,), and a biocompatible tethered vehicle (,) containing a biologically active material is inserted into the cannula along the passageway. A pusher can be inserted within the cannula, behind the vehicle (,), to position the proximal end of the vehicle at the proximal tip of the cannula (,). Once the vehicle (,) is positioned near the proximal end of the cannula (,), the cannula is removed from the passageway, followed by the pusher, leaving the vehicle (,) positioned at the treatment site (,).

Implantable therapy systems and methods

Implantable biocompatable immunoisolatory vehicle for delivery of

A mixer for the mixing of components, comprising a continuous inner surface that is non-retaining to the components, wherein a first portion of the inner surface opposably contacts a second portion of the inner surface during mixing, and a means for supplying a component to the mixer; a kit including the mixer, and methods of using the mixer to prepare compositions.

Mixing device

A method for treatment of a neurodegenerative condition in a patient comprising implanting in the patient at least one immunoisolatory vehicle comprising a corc comprising a volume of at least 1 .mu.l and at least 10.sup.4 living cells which secrete at least one biologically active product, said cells being dispersed in a biocompatible matrix comprising a hydrogel or extracellular matrix components, and an external jacket surrounding the core, the jacket comprising a biocompatible hydrogel or thermoplastic, the jacket being free of cells projecting externally thereof, said jacket having a molecular weight cutoff permitting the passage of the biologically active product from the core through the jacket.

Methods for treatment or prevention of neurodegenerative conditions

A method for treating diabetes in a patient comprising subcutaneously implanting in the patient at least one immunoisolatory vehicle comprising a core comprising a volume of at least 1 .mu.l and at least about 10.sup.4 living cells which secrete insulin, said cells being dispersed in a biocompatible matrix comprising a hydrogel or extracellular matrix components, and a surrounding external jacket of a biocompatible thermoplastic or hydrogel free of said cells projecting externally thereof, said jacket being permselective and immunoisolatory, said jacket having a molecular weight cutoff permitting passage of molecules between the patient and core through said jacket wherein the insulin is released from the immunoisolatory vehicle into the patient's body to treat diabetes.

Methods for treating diabetes by delivering insulin from biocompatible

A method of forming an implantable and retrievable immunoisolatory vehicle is disclosed, the method comprising the steps of first forming a jacket of biocompatible thermoplastic or hydrogel, and then loading the jacket with a core comprising a volume of at least 1 .mu.l and at least 10.sup.4 cells capable of secreting a biocompatible matrix comprising a hydrogel or extracellular matrix, said jacket having a molecular weight cutoff permitting passage of molecules thereacross to provide said biologically active product or said function.

Methods for making immunoisolatory implantable vehicles with a

Immunoisolatory vehicles having a core and a surrounding jacket are disclosed, the core having a volume in excess of 1 .mu.l and at least about 10.sup.4 living cells capable of secreting a biologically active product or of providing a biological function to a patient, the cells dispersed in a biocompatible matrix formed of a hydrogel or an extracellular matrix component, and the external jacket being permselective, biocompatible and having a molecular weight cutoff permitting passage of molecules between the patient and the core through said jacket to provide said biological product or function.

Implantable biocompatible immunoisolatory vehicle for delivery of

A method of making an immunoisolatory vehicle comprised of a core comprising living cells dispersed in a biocompatible matrix is disclosed, the cells being capable of secreting a biologically active product or of providing a metabolic or immunologic function to an individual, and an external jacket surrounding said core which is a biocompatible, permselective thermoplastic or hydrogel, said jacket being free of said cells, comprising coextruding a suspension comprising said cells dispersed in a precursor matrix material comprising extracellular matrix components or a biocompatible hydrogel precursor, and a solution of a biocompatible jacket precursor from a nested dual-bore extrusion nozzle, wherein the suspension of (a) is coextruded from the inner bore and the solution of (b) is coextruded from the outer bore of the nozzle, to form said jacket as the solution of (b) and the suspension of (a) arc coextruded; and exposing the vehicle to a treatment that forms a core comprising a volume of at least 1 .mu.l and at least 10.sup.4 cells and comprising a biocompatible matrix from the precursor matrix of solution (a).

Methods for coextruding immunoisolatory implantable vehicles with a

A mixer for the mixing of a first and a second component, comprising a flexible pouch which contains said first component and which has an inner surface that is non-retaining to the components; means for supplying the second component to the chamber for mixing with the first component; and a neck attached to said pouch.

Implantable therapy systems are disclosed for the local and controlled delivery of a biologically active factor to the brain, spinal cord and other target regions of a subject suffering from a debilitating condition. The method of the invention involves surgically exposing an insertion site, generally located above a predetermined treatment site (12), in a patient. A cannula (20), having an obturator (30) or dilator (104) positioned therein, is inserted at the insertion site, defining a pathway to the treatment site. In some instances, the cannula can be inserted along the path of a guidewire (102) previously positioned at the treatment site. The cannula (20) is preferably a low friction polymeric material such as polytetrafluoroethylene. The cannula (20) generally has an open proximal end for receiving the obturator (30) or dilator (104), and an open distal end, preferably a tapered end, for delivery of neurologically active factors to the treatment site (12). The obturator (30) is then removed from the cannula (20), and a biocompatible tethered vehicle (40) containing a biologically active material is inserted into the cannula along the passageway. A pusher can be inserted within the cannula, behind the vehicle (40), to position the proximal end of the vehicle at the distal end of the cannula (20b). Once the vehicle (40) is positioned near the distal end of the cannula (20), the cannula is removed from the passageway, followed by the pusher, leaving the vehicle (40) positioned at the treatment site (12).

Briefly stated, the present invention comprises a resuscitation mask for administering artificial respiration to a patient. The respiration mask has a container for defining an interior region between the container and the face of the patient. Two conduits are provided through the container wall in order to define two air flow passageways which are in fluid communication with the internal region. A valve is disposed in one air flow passageway for permitting air flow into the internal region and preventing air flow from the internal region. A vent is provided to reduce pressure within the internal region in response to an increase in pressure within the internal region. The container is generally cup-shaped and, in the preferred embodiment, it is formed with a cylindrical member coupled to the one-way air flow conduit. The other airflow passageway is adapted to be detachably coupled to an oxygen source. A pressure openable closure permits pressure within the interior region of the resuscitation mask to be released by a further conduit.

Resuscitation mask having ribs in the air flow conduit and mask body

Growing community of inventors

Cranston, RI, United States of America

Alfred V Vasconcellos