Hybrid soft tissue implants from progenitor cells and biomaterials
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.
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 0.0001×10 6 cells ml −1 to 1000×10 6 cells ml −1 .
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 cm 3 to 100 cm 3 .
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.