HYBRID SOFT TISSUE IMPLANTS FROM PROGENITOR CELLS AND BIOMATERIALS

• US 20100305696A1
• Filed: 05/23/2008
• Published: 12/02/2010
• Est. Priority Date: 05/24/2007
• Status: Active Grant

• 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.
• Granted Patent: US 9,199,002 B2
• Time in Patent Office: Days
• US Class Current: 623/8
• 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

1-57. -57. (canceled)

58. A hybrid soft tissue construct comprising:

a core material;

a biomaterial matrix; and

mammalian cells;

wherein

the core material is acellular and biocompatible;

the biomaterial matrix comprises the mammalian cells; and

the biomaterial matrix covers the acellular core.

59. The construct of claim 58, wherein the mammalian cells comprise adipose cells, interstitial cells, endothelial cells, smooth muscle cells, progenitor cells thereof, or a combination thereof.

60. The construct of claim 58, 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.

61. The construct of claim 58, wherein the construct is a soft tissue implant for the breast, face or hand.

62. The construct of claim 61, wherein the construct is a breast implant.

63. The construct of claim 58, wherein the core material is (i) a conventional saline or silicone gel implant, or (ii) a solid, high-cohesive, form-stable implant.

64. The construct of claim 58, wherein the core material or the biomaterial matrix comprises a polymeric hydrogel.

65. The construct of claim 64, wherein the polymeric hydrogel comprises a polyethylene glycol diacrylate (PEDGA) hydrogel.

66. The construct of claim 58, wherein the biomaterial matrix comprises at least one physical channel.

67. The construct of claim 66, wherein the at least one physical channel does not expose the core material to host tissue and the at least one physical channel has an average diameter of about 0.1 mm to about 5 mm.

68. The construct of claim 58, wherein the biomaterial matrix comprises a growth factor selected from the group consisting of bFGF, VEGF and PDGF.

69. The construct of claim 58, wherein the progenitor cells are present in the biomaterial matrix at a density of about 0.0001×

10⁶ cells ml<sup>−

1</sup> to about 1000×

10⁶ cells ml<sup>−

1</sup>.

70. The construct of claim 58, wherein the progenitor 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.

71. The construct of claim 58, wherein an adipose cell layer covers the core material.

72. A method of forming a hybrid soft tissue construct of claim 58, the method comprising:

providing

mammalian cells,

a biomaterial matrix and

a core material;

contacting the mammalian cells and the biomaterial matrix;

contacting the biomaterial matrix and the core material; and

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

73. The method of claim 72, comprising inserting then withdrawing a capillary tube into the biomaterial matrix to form at least one physical channel such that the at least one physical channel does not expose the core material.

74. The method of claim 72, wherein:

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

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

the at least one physical channel is prepared by placing a capillary tube radially at a location where the hydrogel with cells is contacted with the core material before the hydrogel is so contacted; and

the capillary tube is removed after the hydrogel and cells contact the core material and the hydrogel hardens.

75. The method of claim 72, wherein incubation occurs substantially in vitro.

76. The method of claim 72, wherein incubation occurs substantially in vivo.

77. A method of augmenting or reconstructing a soft tissue of a mammal, the method comprising:

providing the hybrid soft tissue construct of claim 58; and

implanting the engineered hybrid soft tissue construct into a mammal.