Collagen matrix beads for soft tissue repair

• US 4,837,285 A
• Filed: 09/08/1987
• Issued: 06/06/1989
• Est. Priority Date: 03/27/1984
• Status: Expired due to Term

• Current Assignee: Medimatrix, University of Medicine and Dentistry of New Jersey (State of New Jersey)
• Original Assignee: Medimatrix
• Inventors: Pachence, James M., Berg, Richard A., Silver, Frederick H.
• Primary Examiner(s): Kight, John
• Assistant Examiner(s): Nutter, Nathan M.
• Application Number:
  US07/093,826
• Time in Patent Office: 637 Days
• Field of Search: 530/356, 128/DIG. 8, 128/156, 524/17, 524/21, 527/201, 523/105
• US Class Current: 530/356
• CPC Class Codes: A61K 9/70 Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug hollow drug-filled fibres A61K9/0092
• CPC Class Codes: A61L 15/325 Collagen
• CPC Class Codes: A61L 15/44 Medicaments
• CPC Class Codes: A61L 15/64 specially adapted to be resorbable inside the body
• CPC Class Codes: A61L 2300/232 Monosaccharides, disaccharides, polysaccharides, lipopolysaccharides
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/412 Tissue-regenerating or healing or proliferative agents
• CPC Class Codes: A61L 27/24 Collagen
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body
• CPC Class Codes: C08L 89/06 derived from leather or skin , e.g. gelatin
• CPC Class Codes: Y10S 128/08 Collagen

Abstract

Collagen-based compositions for augmenting soft tissue, wound dressings, implants, injectable formulations or other drug delivery systems, comprising resorbable collagen matrix beads, the beads having an average pore size of from 50 to 350 microns, and the collagen comprising from 1 to 30% by volume of the beads, the collagen matrix being sufficiently open to stimulate cellular ingrowth therethrough and yet sufficiently stiff and non-compressible to fill and protect a wound, and the formulation being sufficiently moisture and gas permeable to prevent liquid pooling on a wound and to permit sufficient oxygen diffusion for promoting wound healing.

Claims

1. A wound dressing or implant comprising resorbable, porous collagen matrix beads having particle sizes of from about 100 to 4000 microns, the beads having an average pore size of from about 50 to 350 microns, and the collagen comprising from 1 to 30% by volume of the beads, the porous collagen matrix forming a skeleton providing a volume sufficient for cells to attach and grow into the matrix and being stiff and non-compressible to a degree sufficient to fill and protect a wound, the dressing or implant having a degree of moisture and gas permeability sufficient to prevent liquid pooling on a wound and to permit sufficient oxygen diffusion for promoting wound healing.

2. The wound dressing of claim 1 wherein the collagen matrix beads are prepared from Type I or Type III collagen.

3. The wound dressing of claim 1 wherein the collagen matrix beads are in the form of a dry powder.

4. The wound dressing of claim 1 wherein the collagen matrix has a pore volume of from 80 to 99% by volume, and the matrix is constituted of fibers having a thickness of from 5 to 35 microns and has a stiffness of from 10³ N/m² to 10⁵ N/m².

5. The wound dressing of claim 1 further comprising a macromolecule for promoting tissue ingrowth.

6. The wound dressing of claim 5 wherein the macromolecule is hyaluronic acid or fibronectin, or mixtures thereof.

7. The wound dressing of claim 5, wherein the macromolecule is transforming growth factor beta, platelet-derived growth factor, or a mixture thereof.

12. A method for augmenting wound healing or soft tissue repair in mammals, comprising topically applying or implanting the composition of claim 1.

14. A wound dressing or implant as set forth in claim 1, wherein said beads have partizle sizes from about 300 to 500 microns.

15. A composition as set forth in claim 1, wherein said beads have particle sizes of from about 300 to 500 microns.

8. A compostion for injection into a wound site in mammals for promoting soft tissue augmentation, comprising a suspension of resorbable, porous native collagen matrix beads having particle sizes of about 100 to 4000 microns in an aqueous medium, the beads having an average pore size of 50 to 350 microns, the collagen comprising from 1 to 30% by volume of the beads, the porous collagen matrix beads forming a skeleton providing a volume sufficient for cells to attach and grow into the matrix, and being stiff and non-compressible to a degree sufficient to conform to the tissue to be repaired.

9. The composition of claim 8, wherein the suspension comprises the collagen matrix beads in an aqueous solution of a macromolecule for promoting tissue ingrowth.

10. The composition of claim 8, wherein the suspension comprises collagen matrix beads in admixture with an aqueous solution of transforming growth factor beta, platelet-derived growth factor, hyaluronic acid, fibronectin or mixtures thereof.

11. The composition of claim 8, wherein the collagen matrix has a pore volume of from 80 to 99% by volume, and the matrix is constituted of fibers having a thickness of from 5 to 35 microns and has a stiffness of from 10³ to 10⁵ N/m².

13. A method for augmenting soft tissue repair in mammals, comprising injecting the composition of claim 8 subcutaneously into a patient.