Extracellular matrix (ECM) structures for tissue regeneration

• US 9,700,654 B2
• Filed: 08/06/2014
• Issued: 07/11/2017
• Est. Priority Date: 05/10/2007
• Status: Active Grant

• Current Assignee: Elutia Med LLC
• Original Assignee: Cormatrix Cardiovascular, Inc.
• Inventors: Matheny, Robert G, Ferrante, Craig N
• Primary Examiner(s): Chen, Shin Lin
• Application Number:
  US14/452,794
• Publication Number:
  US 20150359942A1
• Time in Patent Office: 1,070 Days
• Field of Search: 424423, 424551, 424572, 530350
• CPC Class Codes: A61F 2/02 Prostheses implantable into the body closure means for urethra or rectum or for artificial body openings therefor A61F2/0004
• CPC Class Codes: A61F 2210/0076 multilayered, e.g. laminated structures
• 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 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61K 35/38 Stomach; Intestine; Goblet cells; Oral mucosa; Saliva
• CPC Class Codes: A61K 35/545 Embryonic stem cells; Pluripotent stem cells; Induced pluripotent stem cells; Uncharacterised stem cells
• CPC Class Codes: A61K 38/18 Growth factors; Growth regulators
• CPC Class Codes: A61K 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence
• CPC Class Codes: A61L 2300/414 Growth factors
• CPC Class Codes: A61L 2430/00 Materials or treatment for tissue regeneration
• CPC Class Codes: A61L 27/3633 Extracellular matrix [ECM]
• CPC Class Codes: A61L 27/3683 subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
• CPC Class Codes: A61L 27/3834 Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges

Abstract

A multi-sheet extracellular matrix (ECM) structure for tissue regeneration, the ECM structure having joined first and second ECM sheet members and an agent dispersal network disposed between the sheets, the dispersal network being configured to receive and transfer a bioactive agent through the network and, when the ECM structure is attached to tissue, administer the bioactive agent to the tissue.

Claims

1. An extracellular matrix (ECM) structure for tissue regeneration, comprising:

a multi-sheet structure comprising a first sheet member having first top and bottom surfaces and a second sheet member having second top and bottom surfaces, said first and second sheet members being joined proximate said first sheet member first bottom surface and said second sheet member second top surface,

said first and second sheet members comprising an ECM composition comprising decellularized ECM derived from small intestine submucosa (SIS), said decellularized ECM comprising endogenous glycosaminoglycans (GAGs), transforming growth factor-beta (TGF-β

), fibroblast growth factor-2 (FGF-2) and vascular epithelial growth factor (VEGF),

said multi-sheet structure being configured to modulate inflammation of damaged tissue and not elicit an adverse inflammatory response of said damaged tissue, and induce neovascularization, host tissue proliferation, bioremodeling of said damaged tissue and regeneration of new tissue and tissue structures with site specific structural and functional properties, when said multi-sheet structure is delivered to said damaged tissue; and

an agent dispersal network member comprising a biodegradable polymeric material, said agent dispersal network member being disposed between said first and second sheet members proximate said first sheet member first bottom surface and said second sheet member second top surface, said agent dispersal network member comprising a sealed, continuous structure comprising a plurality of mating channels that are configured to receive a bioactive agent therein and disperse said bioactive agent into said first and second sheet members, wherein, when said multi-sheet structure is delivered to said damaged tissue, said bioactive agent is transferred thereto.

2. The ECM structure of claim 1, wherein said agent dispersal network member further comprises at least one opening that is in communication with said mating channels.

3. The ECM structure of claim 1, wherein said agent dispersal network member comprises a porous network member having a continuous lumen that is configured to receive and transfer said bioactive agent therein, and disperse said bioactive agent therefrom.

4. The ECM structure of claim 3, wherein said biodegradable polymeric material comprises a polymeric material selected from the group consisting of polyhydroxyalkonates (PHAs), polylactides (PLLA), polyglycolides (PLGA) and polyanhydrides.

5. The ECM structure of claim 1, wherein said ECM composition further comprises at least one exogenously added biologically active agent.

6. The ECM structure of claim 5, wherein said biologically active agent comprises fibroblast growth factor-2 (FGF-2).

7. The ECM structure of claim 1, wherein said first sheet member further comprises a porous structure.

8. The ECM structure of claim 1, wherein said second sheet member further comprises a porous structure.