Fabrication of bone regeneration scaffolds and bone filler material using a perfusion flow system

Patent metadata

Field	Value
Publication number	US-9770533-B2
Application number	US-201514728336-A
Country	US
Kind code	B2
Filing date	Jun 2, 2015
Priority date	Dec 19, 2012
Publication date	Sep 26, 2017
Grant date	Sep 26, 2017

Abstract

The present disclosure is directed at a process to form bone grafting material. One may provide a porous collagen scaffold and insert the scaffold into a perfusion chamber of a perfusion flow system. This may then be followed by continuously providing a mineralization perfusion fluid flow through the scaffold at a flow rate to provide dynamic intrafibrillar mineralization of the scaffold and form a collagen/hydroxyapatite composite scaffold. One may optionally provide the scaffold with bone tissue forming cells and then deliver a perfusion fluid including oxygen and one or more nutrients through the collagen/hydroxyapatite composite scaffold and to the bone tissue forming cells at a flow rate such that the bone tissue forming cells remodel the collagen/hydroxyapatite composite scaffold and form a bone tissue extracellular matrix. The bone tissue extracellular matrix may then be decellularized to form an acellular bone repair scaffold.

First claim

What is claimed is:

1. A process to form a bone grafting material, comprising:
providing a porous collagen scaffold containing collagen fibers;
inserting the collagen scaffold into a perfusion chamber of a perfusion flow system;
continuously providing a mineralization perfusion fluid flow through the collagen scaffold at a flow rate through said collagen scaffold of 1 μm/s to 10 mm/s, said mineralization fluid containing an ion-containing extracellular fluid, which supplies mineral ions to said collagen scaffold such that hydroxyapatite (HA) crystals form on said collagen fibers and wherein said collagen scaffold has a geometry that inhibits said mineralization perfusion fluid from flowing around said scaffold rather than through said scaffold.

2. The process of claim 1 including:
providing the scaffold with bone tissue forming cells and delivering a perfusion fluid including oxygen and one or more nutrients through the collagen scaffold with said HA crystals and to the bone tissue forming cells at a flow rate such that the bone tissue forming cells remodel the collagen/hydroxyapatite composite scaffold and form a bone tissue extracellular matrix.

3. The process of claim 2 wherein said bone tissue extracellular matrix is decellularized and forming an acellular bone repair scaffold.

4. The process of claim 3 wherein the acellular bone repair scaffold is placed in a treatment site of a host to be treated.

5. The process of claim 2 wherein said perfusion fluid including oxygen and one or more nutrients comprises an osteogenic induction medium.

6. The process of claim 1 wherein said mineralization perfusion fluid is provided at a continuous flow rate of 20 μm/s to 500 μm/s.

7. The process of claim 1 wherein said mineralization perfusion fluid is provided at a continuous flow for a period of 12 hours to 7 days.

8. The process of claim 1 wherein said collagen scaffold has an outer portion and an inner portion and said hydroxyapatite crystals are deposited on said inner portion and outer portion, wherein said hydroxyapatite crystals are deposited substantially uniformly through the collagen scaffold.

9. The process of claim 1 wherein said perfusion flow system comprises a closed-loop perfusion flow system comprising a source container for said mineralization perfusion fluid, a pump to continuously provide said mineralization fluid to said collagen scaffold and a temperature controlled chamber to pass said mineralization fluid through said collagen scaffold and return said mineralization fluid to said source container.

10. The process of claim 9 wherein said temperature controlled chamber is maintained at body temperature.

11. A process to form a bone grafting material, comprising:
providing a porous collagen scaffold containing collagen fibers;
inserting the collagen scaffold into a perfusion chamber of a perfusion flow system;
continuously providing a mineralization perfusion fluid flow through the collagen scaffold at a flow rate through said collagen scaffold of 1 μm/s to 10 mm/s, said mineralization fluid containing an ion-containing extracellular fluid, which supplies mineral ions to said collagen scaffold such that hydroxyapatite crystals form on said collagen fibers and wherein said collagen scaffold has a geometry that inhibits said mineralization perfusion fluid from flowing around said scaffold rather than through said scaffold;
providing the collagen scaffold with said HA crystals with bone tissue forming cells and delivering a perfusion fluid including oxygen and one or more nutrients through the collagen scaffold with said HA crystals and to the bone tissue forming cells at a flow rate such that the bone tissue forming cells remodel the collagen scaffold with said HA crystals and form a bone tissue extracellular matrix; and
removing said bone tissue extracellular matrix and forming an acellular bone repair scaffold.

12. The process of claim 11 wherein said mineralization perfusion fluid is provided at a continuous flow rate of 20 μm/s to 500 μm/s.

13. The process of claim 11 wherein said mineralization perfusion fluid is provided at a continuous flow for a period of 12 hours to 7 days.

14. The process of claim 11 wherein said perfusion fluid including oxygen and one or more nutrients comprises an osteogenic induction medium.

15. The process of claim 11 wherein the acellular bone repair scaffold is placed in a treatment site of a host to be treated.

Assignees

• Southwest Res Inst

Inventors

• Ling Jian
• Antebi Ben
• Cheng Xingguo
• Harris Jeffrey N
• Chen Xiao-Dong

Classifications

• A61L27/56

  Porous materials, {e.g. foams or sponges} · CPC title

• A61L2300/412

  Tissue-regenerating or healing or proliferative agents · CPC title

• A61L27/46 Primary

  with phosphorus-containing inorganic fillers · CPC title

• A61L27/54

  Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)} · CPC title

• A61L27/3821

  Bone-forming cells, e.g. osteoblasts, osteocytes, osteoprogenitor cells · CPC title