Biohybrid Technologies LLC

W. R. Grace Co.-conn.

Other

Sensor Technologies, Inc.

Biohybrio Technologies LLC

William L Chick

Robert P Lanza

Willem M Kuhtreiber

Pierre M Galletti

Susan J Sullivan

David E Wolf

Georg Panol

Richard A Cardullo

Peter D Richardson

Edward J Doherty

Karen E Dunleavy

Barry A Solomon

Kermit M Borland

Amy L Foley

Randall G Rupp

Dawn M Ecker

Joanne P Marsh

Thomas E Muller

John M Harvey

John Ringeling

Donald P King, Jr

Implantable devices that include a source of a therapeutic substance and a capture agent are disclosed.

Devices for cloaking transplanted cells

A device that includes a living cell or tissue and an agent that inhibits the ability of a host molecule to damage the cell or tissue. The device can be constructed in various forms including an implantable device, a composite microreactor and a double composite microreactor. The composite microreactor includes an internal particle that includes a living cell or tissue, an internal particle matrix that includes the living cell or tissue and an internal semipermeable coating enclosing the internal particle matrix, a gel super matrix in which the internal particle is embedded, and an agent that inhibits the ability of a host molecule to damage the cell or tissue. The double composite microreactor includes an internal particle, a particle that includes a particle matrix in which the internal particle is embedded, a super matrix in which the particle is embedded, and an agent that inhibits the ability of a host molecule to damage the living cell or tissue.

Devices containing cells or tissue and an agent that inhibits damage by a host cell molecule

Microcapsules and composite microreactors are prepared that immunoisolate living cells such as islet cells or genetically engineered cells. A reduced volume microcapsule is formed by coating a gel matrix particle with a polyamino acid of 15,000 daltons or less molecular weight to reduce volume of the particle by at least 30% as compared to volume prior to coating. A composite microreactor includes the microcapsule containing cell embedded in a gel matrix and provides a molecular weight cutoff that prevents molecules larger than about 400,000 daltons from containing the living cell. A double composite microreactor includes an internal particle that includes an internal particle gel matrix containing a living cell and having a coating, a particle that includes the internal particle embedded in a particle gel matrix and a coating, and a gel super matrix in which the particle is embedded. At least one of the coatings is a volume reducing coating of polyamino acid of 15,000 daltons or less molecular weight. The gel matrices may be alginate, the polyamino acid may be polylysine or polyornithine, and at least one of the gel matrices or coatings may be treated by aging for between 2 hours and 14 days. The internal particle, particle and composite microreactor may have diameters respectively between 50 and 700 microns, 400 and 800 microns and 300 and 1500 microns. to be implanted so there is little or no need for immunosuppressant or antifibrotic drugs. A reduced volume microcapsule is formed by coating a gel matrix particle with a polyamino acid of 15,000 daltons or less molecular weight to reduce volume of the particle by at least 30% as compared to volume prior to coating. A composite microreactor is provided by embedding the microcapsule when containing a living cell in a gel matrix to obtain a molecular weight cutoff that prevents molecules larger than about 400,000 daltons from contacting the living cell. A double composite microreactor is formed containing an internal particle including an internal particle gel matrix containing a living cell and having a coating, a particle including the internal particle embedded in a particle gel matrix having a coating, and a gel super matrix in which the particle is embedded. At least one of the coatings is a volume reducing coating of polyamino acid of 15,000 daltons or less molecular weight. The gel matrices may be alginate, the polyamino acid may be polylysine or polyornithine, and at least one of the gel matrices or coatings may be treated by aging for between 2 hours and 14 days. The internal particle, particle and composite microreactor may have diameters respectively between 50 and 700 microns, 400 and 800 microns and 300 and 1500 microns.

Microcapsules and composite microreactors for immunoisolation of cells

An in vivo method and apparatus for detecting an analyte in an individual. A sensor that includes a fluorescence reagent is placed in communication with the body fluids of the individual suspected of containing the analyte in such a way that once in place said sensor does not exit the skin of the individual. The sensor is configured to retain the fluorescence reagent while allowing analyte to diffuse into and out of said sensor. The sensor is illuminated transdermally, and the fluorescence from the fluorescence reagent associated with the presence of the analyte is measured.

Methods and device for detecting and quantifying substances in body

The invention covers a method of implanting a living donor cell into a host animal without inflammatory response or rejection of the donor cell by the host animal, by obtaining an uncoated particle of a biocompatible, temperature-independent gel that encapsulates the living donor cell, wherein the uncoated particle provides a molecular weight cutoff that prevents host animal immune cells from entering the particle, yet does not have to prevent entry of host animal IgG and complement into the particle, and implanting the uncoated particle into the host animal.

Methods of use of uncoated gel particles

Methods for inhibition of fibrotic rejection of implanted devices which contain cells by administering to the recipient of the devices an amount of a non-steroidal anti-inflammatory agent (NSAID) sufficient to inhibit fibrotic inactivation of the device. Most NSAID's are carboxylic acids (R--COOH) or enolic acids (R--COH).

Non-steroidal anti-inflammatory agents inhibition of fibrotic response

A method for quantifying glucose concentration in blood, body fluids, and other samples within, below and above the normal physiological range, which relies on non-radiative fluorescence resonance energy transfer, as well as devices useful in quantifying blood glucose concentration using the present method.

Method and device for detecting and quantifying glucose in body fluids

A device which serves as an artificial pancreas comprises a hollow fiber which is surrounded by islets of Langerhans enclosed in a housing. The islets are suspended in a semi-gel matrix or supporting material that is sufficiently viscous to physically support and maintain location of the islets about the hollow fiber, but sufficiently fluid to enable removal of the islet suspension from the device, followed by reseeding or replacement with fresh islet suspension. The matrix in which the islets are suspended preferably comprises calcium sodium alginate. The semi-gel supporting material also enables long term maintenance of islet cells in in vitro culture.

Artificial pancreatic perfusion device with reseedable matrix

A device which serves as an artificial pancreas comprises a hollow fiber which is surrounded by islets of Langerhans enclosed in a housing. The islets are suspended in a temperature sensitive matrix which is sufficiently viscous to support islets at a temperature below about 45.degree. C. and sufficiently fluid to enable removal of islet suspension at a temperature above about 45.degree. C. A warm (e.g., 48.degree. to 50.degree. C.) solution may be flushed through the device to change the physical state of the temperature sensitive matrix from a semi-solid state to a liquified semi-gel state. The temperature sensitive supporting material also enables long term maintenance of islet cells in in vitro culture.

Artificial pancreatic perfusion device with temperature sensitive matrix

A device which serves as an artificial pancreas comprises a hollow fiber having an inner diameter of about 5 mm which is surrounded by islets of Langerhans enclosed in a housing. The islets are suspended in a semi-solid matrix which ensures desired distribution of the cells about the hollow fiber. The hollow fiber and suspended islets are enclosed in a housing which further aids the desired distribution of islets about the hollow fiber. The hollow fiber has a porosity which selectively allows passage of substances having a molecular weight of less than about 100,000 Daltons. The semi-solid matrix in which the islets are embedded and suspended is formed of an appropriate supporting material such as alginate or agar.

Artificial pancreatic perfusion device

A cell culture device for use, e.g., as an artificial pancreas, featuring, in various aspects, a tightly wound spiral tube snugly fit in a cavity to form a cell culture compartment, the spiral being eccentrically offset in the cavity to reduce the volume of the compartment, a sloped passage in the body with an end of the tube extending through the passage to the innermost spiral without bending sharply, the ends of the spiral tube communicating with ports on the same side of the body, and a wall of the cavity facing the spiral and being spaced from the tube to form an end of the compartment to provide for simplified cell loading.

Cell culture device

A cell culture device for use, e.g., as an artificial pancreas, featuring, in various aspects, a semipermeable tube wrapped about a spool and mounted within a cylinder to form a cell culture compartment; an inlet and an outlet strand of the semipermeable tube being wrapped to form alternating adjacent coils to provide improved convective transport; and the semipermeable tube being wrapped to form helical coils to provide improved conductive transport.

Growing community of inventors

Wellesley, MA, United States of America

William L Chick