Structurally modified acellular tissue engineering scaffolds and methods of production
Methods are provided for producing a bioscaffold from natural tissues by oxidizing a decellularized tissue to produce a bioscaffold having pores therein. The pore size and porosity is increased to better accommodate intact cells so that live cells can better infiltrate and inhabit the bioscaffold. The bioscaffold may be freeze-dried or lyophilized, sterilized and (optionally) aseptically packaged for subsequent use. A further aspect of the present invention is a bioscaffold produced by the processes described herein. Methods of treatment using the bioscaffold as a graft or as a biomedical implant for implantation are also provided. Also provided are methods of seeding a bioscaffold with mammalian cells, wherein the seeding carried out either in vitro or in vivo, and wherein a bioscaffold produced as described herein is utilized for said seeding.
1. In a method of producing a bioscaffold by decellularizing a tissue to produce a bioscaffold having pores therein, the improvement comprising:
decellularizing the tissue with an oxidant and detergent simultaneously to remove extraneous material and increase the pore size and porosity therein,
wherein at least 70% of cells are removed from said tissue upon said decellularizing.
2. The method of claim 1 , wherein said oxidant is hydrogen peroxide, peracetic acid, or a mixture thereof.
3. The method of claim 1 , wherein said oxidant is in an aqueous solution at a concentration of between 1 and 32% (w/v).
4. The method of claim 1 , wherein said oxidant is in an aqueous solution at a concentration of between 3 and 32% (w/v).
5. The method of claim 1 , further comprising the step of washing said bioscaffold after said decellularizing step to remove residual oxidant and detergent.
6. The method of claim 5 , further comprising the step of freeze-drying said scaffold following said washing step.
7. The method of claim 5 , further comprising the step of sterilizing said scaffold following said washing step.
8. The method of claim 1 , further comprising the step of removing adventitia from said tissue prior to said decellularizing step.
9. The method of claim 8 , wherein said tissue is a blood vessel.
10. The method of claim 1 , wherein said tissue is selected from the group consisting of skin, muscle, tendon, bone, meniscus, cartilage, intervertebral discs, and ligament tissue.
11. The method of claim 1 , wherein said tissue is selected from the group consisting of liver, kidney, and pancreas tissue.
12. The method of claim 1 , wherein said tissue is nerve tissue.
13. The method of claim 1 , wherein said tissue is cartilage tissue.
14. The method of claim 1 , wherein at least 80% of cells are removed from said tissue upon said decellularizing.
15. The method of claim 1 , wherein at least 90% of cells are removed from said tissue upon said decellularizing.
16. A bioscaffold produced by the process of decellularizing a tissue with an oxidant and detergent simultaneously to remove extraneous material and increase the pore size and porosity therein,
wherein at least 70% of cells are removed from said tissue upon said decellularizing.
17. The bioscaffold of claim 16 , wherein said bioscaffold is sterile.
18. The bioscaffold of claim 16 , wherein said bioscaffold is freeze-dried.
19. The bioscaffold of claim 16 aseptically packaged in a sterile container.
20. The bioscaffold of claim 16 , wherein at least 80% of cells are removed from said tissue upon said decellularizing.
21. The bioscaffold of claim 16 , wherein at least 90% of the cells are removed from said tissue upon said decellularizing.