Hybrid soft tissue implants from progenitor cells and biomaterials

• US 9,199,002 B2
• Filed: 05/23/2008
• Issued: 12/01/2015
• Est. Priority Date: 05/24/2007
• Status: Expired due to Fees

• Current Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Original Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Inventors: Mao, Jeremy J., Moioli, Eduardo K.
• Primary Examiner(s): IWAMAYE, ANDREW MICHAEL
• Application Number:
  US12/601,793
• Publication Number:
  US 20100305696A1
• Time in Patent Office: 2,748 Days
• Field of Search: 623/8, 623 2372- 2376, 427/2.22, 427 224- 226, 427/2.28, 427243-247
• US Class Current: 1/1
• CPC Class Codes: A61F 2/12 Mammary prostheses and implants
• CPC Class Codes: A61F 2210/0061 swellable
• CPC Class Codes: A61F 2210/0076 multilayered, e.g. laminated structures
• CPC Class Codes: A61F 2230/0095 Saddle-shaped
• CPC Class Codes: A61F 2310/00383 Gelatin
• CPC Class Codes: A61F 2310/00994 Coating made of gelatin
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/222 Gelatin
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61L 27/3886 comprising two or more cell types
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: C08L 71/02 Polyalkylene oxides
• CPC Class Codes: C12N 2533/30 Synthetic polymers thermoreactive polymers, e.g. PNIPAm, C12N2539/10
• CPC Class Codes: C12N 5/0653 Adipocytes; Adipose tissue

Abstract

Provided are hybrid soft tissue constructs comprising a core material, a biomaterial matrix and mammalian cells. Also provided are methods of augmenting or reconstructing a soft tissue of a mammal. Additionally, methods of forming a hybrid soft tissue construct are provided. The use of the above constructs for augmenting or reconstructing a soft tissue of a mammal are further provided. Additionally provided is the use of the above constructs for the manufacture of a medicament for augmenting or reconstructing a soft tissue of a mammal.

Claims

1. A method of forming a hybrid soft tissue construct, the hybrid soft tissue construct comprising a core material, a biomaterial matrix, and isolated mammalian cells, the method comprising:

providing the isolated mammalian cells, the biomaterial matrix and the core material;

contacting the mammalian cells and the biomaterial matrix;

contacting the biomaterial matrix and the core material;

forming a plurality of macrochannels in the biomaterial matrix, the plurality of macrochannels not exposing the core material underlying the biomaterial matrix; and

incubating the biomaterial matrix, the mammalian cells, and the core material to form the hybrid soft tissue construct;

wherein,

the biomaterial matrix is a polyethylene glycol diacrylate (PEGDA) hydrogel further comprising the mammalian cells;

the hydrogel with the mammalian cells are contacted with the core material as a liquid then photopolymerized into a gel;

formation of the macrochannels comprises placing capillary tubes radially at locations near the core material before the core material and the hydrogel with the mammalian cells are contacted;

each of the capillary tubes is removed after the hydrogel with the mammalian cells contact the core material and after the hydrogel photopolymerizes into the gel;

the core material is acellular and biocompatible, and designed to remain acellular upon implantation in a subject;

the biomaterial matrix comprises a plurality of microchannel pores throughout the biomaterial matrix;

the plurality of macrochannels have an average diameter of 0.1 mm to 50 mm;

the plurality of macrochannels does not expose the core material to host tissue; and

the biomaterial matrix contacts and covers the acellular core.

2. The method of claim 1, wherein the mammalian cells comprise adipose cells, interstitial cells, endothelial cells, smooth muscle cells, progenitor cells thereof, or a combination thereof.

3. The method of claim 1, wherein the mammalian cells comprise (i) adipose cells, (ii) progenitor cells selected from the group consisting of adipose tissue derived cells, pre-adipocytes, mesenchymal stem cells (MSC), MSC-derived cells, and adipocytes, or (iii) a combination thereof.

4. The method of claim 1, wherein the construct is a soft tissue implant for a breast, a face or a hand.

5. The method of claim 1, wherein the construct is a breast implant.

6. The method of claim 1, wherein the core material is (i) a saline or silicone gel implant, or (ii) a solid, high-cohesive, form-stable implant.

7. The method of claim 1, wherein the plurality of macrochannels have an average diameter of 2.5 mm to 50 mm.

8. The method of claim 1, wherein the biomaterial matrix comprises a growth factor selected from the group consisting of bFGF, VEGF and PDGF.

9. The method of claim 1, wherein the mammalian cells are present in the biomaterial matrix at a density of 0.0001×

10⁶ cells ml<sup>−

1</sup> to 1000×

10⁶ cells ml<sup>−

1</sup>.

10. The method of claim 1, wherein the mammalian cells comprise a first progenitor cell and a second progenitor cell, the first progenitor cell is an adipose progenitor cell, and the second progenitor cell is a vascular progenitor cell.

11. The method of claim 1, wherein a layer comprising isolated adipose cells covers the core material.

12. The method of claim 1, wherein incubation occurs in vitro.

13. The method of claim 1, wherein incubation occurs in vivo.

14. The method of claim 1, wherein incubation occurs in vitro and in vivo.

15. The method of claim 1, wherein the acellular core material has a volume of 0.5 cm³ to 100 cm³.

16. The method of claim 1, the core material is selected from the group consisting of an artificial implant material, a breast implant material, a saline implant, a silicone gel implant, a multiple lumen design implant, a gummy bear implant, a solid implant, a high-cohesive implant, and a form-stable implant;

and

the core material is suitable to be functionalized by surrounding autologous engineered adipose tissue from progenitor cells.

17. The method of claim 1, further comprising coating the core material with an elastomer or polyurethane foam.