Bioartificial devices and cellular matrices therefor

• US 5,834,005 A
• Filed: 12/07/1995
• Issued: 11/10/1998
• Est. Priority Date: 02/24/1992
• Status: Expired due to Term

• Current Assignee: Encelle, Inc. (Surgalign Holdings, Inc.)
• Original Assignee: Encelle, Inc. (Surgalign Holdings, Inc.)
• Inventors: Usala, Anton-Lewis
• Primary Examiner(s): AZPURU, CARLOS A
• Application Number:
  US08/568,482
• Time in Patent Office: 1,069 Days
• Field of Search: 424/423, 424/424, 435/1.14, 435/182, 623/11, 514/772.3
• US Class Current: 424/424
• CPC Class Codes: A01N 1/02 Preservation of living parts
• CPC Class Codes: A01N 1/0231 Chemically defined matrices, e.g. alginate gels, for immobilising, holding or storing cells, tissue or organs for preservation purposes; Chemically altering or fixing cells, tissue or organs, e.g. by cross-linking, for preservation purposes
• CPC Class Codes: A61F 2/022 Artificial gland structures using bioreactors hemodialysis A61M1/16; hemofiltration A61M1/34; other extracorporeal blood treatment A61M1/36
• CPC Class Codes: A61F 2310/00365 Proteins; Polypeptides; Degradation products thereof
• CPC Class Codes: A61K 2035/126 Immunoprotecting barriers, e.g. jackets, diffusion chambers
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61L 27/222 Gelatin
• CPC Class Codes: A61L 27/24 Collagen
• CPC Class Codes: A61L 27/26 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: C12N 2500/05 Inorganic components
• CPC Class Codes: C12N 2500/32 Amino acids
• CPC Class Codes: C12N 2509/00 Methods for the dissociation of cells, e.g. specific use of enzymes
• CPC Class Codes: C12N 2533/30 Synthetic polymers
• CPC Class Codes: C12N 2533/54 Collagen; Gelatin
• CPC Class Codes: C12N 2533/70 Polysaccharides
• CPC Class Codes: C12N 5/0012 Cell encapsulation
• CPC Class Codes: C12N 5/0677 Three-dimensional culture, tissue culture or organ culture; Encapsulated cells

Abstract

A device for the effective release of cellular moieties, including hormones, wherein a matrix containing a hormone producing cellular moiety is encapsulated with a non-immunogenic polymeric material of poly-para-xylylene or other aromatic based polymer moiety having a membrane portion with a porosity blocking passage therethrough of immunogenic agents and permitting passage therethrough of effective nutrients for said cellular moiety and the hormone produced thereby, an improved matrix for the storage, manufacture, functional testing, and viral infection testing of cellular moieties wherein a collagen based hydrogel is processed to present a liquid phase at host temperature and functions as a substrate for cellular attachment with additives effective for limiting thermal and pressure trauma, and an improved method for the harvesting tissue from organs.

Claims

1. A bioartificial implantable device comprising capsule means, a hydrogel matrix containing a cellular moiety releasing a therapeutically desirable entity, said matrix comprising gelatin in a concentration of about 0.01 to 30 mM, a liquid in an amount of about 15 to 96.5 percent by weight, and a nitric oxide inhibitor in the concentration of about 0.001 to 300 mM, and a semi-permeable membrane vacuum deposited over said capsule means, said membrane comprising poly-para-xylylene having a molecular weight porosity between the molecular weight of said entity and about 40,000.

2. The device as recited in claim 1 wherein said matrix includes a divalent chelator present in the concentration of about 0 to 100 mM.

3. The device as recited in claim 1 wherein said matrix includes antibiotics in an amount of about 0 to 10 percent by weight.

4. A device for releasing a biological agent in a recipient patient comprising:

a matrix containing a cellular moiety producing a biological agent, and capsule means enveloping said matrix comprising a polymeric membrane selected from the group comprising para-xylylene, poly-monochloro-xylene, and poly-dichloro-xylylene of poly-para-xylylene, said polymeric membrane having a porosity blocking passage therethrough of immunogenic agents while permitting passage therethrough of said biological agent and nutrients for said cellular moiety.

5. A drug delivery device comprising a matrix containing cells releasing a biological agent, said matrix at least partially enveloped by a conformal membrane selected from the group comprising para-xylylene, poly-monochloro-xylylene, and poly-dichloroxylylene, said conformal membrane having a molecular weight porosity of between about 5,000 and 40,000.

6. A device for releasing hormones in a recipient patient comprising:

a matrix containing a hormone producing cellular moiety and capsule means enveloping said matrix comprising a polymeric membrane of poly-para-xylylene having a porosity blocking passage therethrough of immunogenic agents and permitting passage therethrough of nutrients for said cellular moiety and the hormone produced thereby.

7. The device as recited in claim 6 wherein said polymeric membrane is selected form the group consisting of poly-para-xylylene, poly-monochloro-xylylene, and poly-dichloro-xylylene.

8. The device as recited in claim 7 wherein said membrane has a thickness of around 2000 to 5000 Angstroms.

9. A process for making a device for releasing a biological agent comprising the steps of:

forming a matrix including a bilogical agent producing cellular moiety; and

covering said matrix with a non-immunogenic polymeric material comprising poly-para-xylylene with at least a portion of said polymeric material being in the form of a membrane having said porosity blocking passage therethrough of immunogenic agents while permitting passage therethrough of effective nutrients for said cellular moiety and the hormone produced thereby.

10. A bioartificial implantable device comprising a cellular moiety in a hydrogel matrix encapsulated by a semi-permeable membrane, said matrix comprising gelatin in a amount of about 0.01 to 30 mM, a liquid in the amount of about 15 to 96.5 percent by weight, and a nitric oxide inhibitor in an amount of about 0.01 micromolar to 300 mM said membrane having a blocking passage therethrough of immunogenic agents while permitting passage therethrough of nutrients and a biological agent of interest.

11. A bioartificial implantable device of claim 10 wherein said cellular moiety produces a therapeutically desirable entity, and said membrane comprises poly-para-xylylene having a molecular weight porosity between the molecular weight of said entity and about 40,000.

12. The device as recited in claim 10 wherein said matrix includes a divalent chelator present in the concentration of about 0.001 to 100 mM.

13. The device as recited in claim 10 wherein said matrix includes an antibiotic in an amount of about 0.01 micromolar to 300 mM.

14. A bioartificial implantable device comprising a cellular moiety in a hydrogel matrix encapsulated by a semi-permeable membrane, said matrix comprising gelatin in an amount of about 0.01 to 30 mM, a liquid in the amount of about 15 to 96.5 percent by weight, and a nitric oxide inhibitor in an amount of about 0.01 micromolar to 300 nM, said membrane having a blocking passage therethrough of immunogenic agents while permitting passage therethrough of nutrients and a biological agent of interest.

15. A bioartificial implantable device of claim 14 wherein said cellular moiety produces a therapeutically desirable entity, and said membrane comprises poly-para-xylylene having a molecular weight porosity between the molecular weight of said entity and about 40,000.

16. The device as recited in claim 14 wherein said matrix includes a divalent chelator present in the concentration of about 0.001 to 100 mM.

17. The device as recited in claim 14 wherein said matrix includes antibiotics in an amount of about 0.01 micromolar to 300 mM.