ULTRASOUND ACCELERATED TISSUE ENGINEERING PROCESS

• US 20070299539A1
• Filed: 04/12/2007
• Published: 12/27/2007
• Est. Priority Date: 04/12/2006
• Status: Abandoned Application

• Current Assignee: Board of Trustees of The University of Illinois
• Original Assignee: Board of Trustees of The University of Illinois
• Inventors: Othman, Shadi, Halim, Nadia, Mouannes, Jessy, Vidula, Neelima, Magin, Richard
• Application Number:
  US11/734,612
• Publication Number:
  US 20070299539A1
• Time in Patent Office: Days
• US Class Current: 623/23.72
• CPC Class Codes: A61K 2035/124 the cells being hematopoietic, bone marrow derived or blood cells
• CPC Class Codes: C12M 35/04 Mechanical means, e.g. sonic waves, stretching forces, pressure or shear stimuli
• CPC Class Codes: C12N 2521/10 Sound, e.g. ultrasounds
• CPC Class Codes: C12N 5/00 Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor; plant reproduction by tissue culture techniques A01H4/00

Abstract

In an aspect the invention is a method of preparing a cell or tissue implant for insertion into a patient in need of treatment by obtaining a transplantable cell population, culturing the cell population in a culture media and exposing the cell population to a sonic or ultrasonic stimulation, wherein the stimulation provides a capability for an enhanced implant outcome parameter. The method provides enhanced autologous bone implant procedures by reducing the time required for a patient'"'"'s own cells to sufficiently undergo osteogenesis, thereby reducing the waiting time for an autologous bone implant. The extent of osteogenesis is optionally monitored non-invasively by magnetic resonance spectroscopy.

Claims

1. A method of preparing a cell or tissue implant for insertion into a patient in need of treatment, said method comprising:

obtaining a transplantable cell population;

culturing said cell population in a culture media; and

exposing said cell population to a sonic or ultrasonic stimulation, wherein said stimulation provides a capability for an enhanced implant outcome parameter.

2. The method of claim 1 further comprising:

providing a biocompatible scaffold; and

introducing said cell population to said scaffold.

3. The method of claim 2, wherein said stimulation occurs after said introducing step.

4. The method of claim 1, wherein said implant outcome parameter is selected from one or more of the group consisting of:

accelerated cell growth or proliferation;

reduced time for implant generation;

increased mineral deposition; and

increased osteogenesis.

5. The method of claim 1, wherein said cell population is obtained from said patient.

6. The method of claim 5 further comprising expanding said cell population prior to said introducing step.

7. The method of claim 6, wherein said introducing step comprises applying said cells having a concentration selected from a range of between 1×

10⁶ to 1×

10⁷ cells/mL to said biocompatible scaffold.

8. The method of claim 1, wherein said cell population is not obtained from said patient.

9. The method of claim 1, wherein said cell population comprises mesenchymal stem cells.

10. The method of claim 9, further comprising differentiating at least a portion of said mesenchymal stem cells into osteoblast cells prior, during, or prior and during said ultrasonic stimulation.

11. The method of claim 1, wherein said sonic or ultrasonic stimulation has:

an operating frequency of between 10 Hz and 10 MHz; and

a pulse repetition rate selected from between 500 Hz and 5 kHz

12. The method of claim 1, wherein said stimulation is a low-intensity ultrasonic stimulation having:

an intensity of 30 mW/cm²;

an operating frequency of 1.5 MHz;

a pulse width of 200 μ

sec; and

a pulse repetition rate of 1 kHz.

13. The method of claim 1, wherein the ultrasound is applied daily, with each daily treatment having a daily treatment duration selected from a range between 10 minutes and 30 minutes and wherein the daily treatment is repeated from a range between 5 days and 21 days.

14. The method of claim 13, wherein the daily treatment is about 20 minutes per day.

15. The method of claim 1, further comprising implanting said implant into a patient.

16. The method of claim 1, wherein said implant is a bone implant and said outcome parameter comprises accelerated osteogenesis resulting in a decreased time required for bone implant generation compared to a bone implant not exposed to said sonic or ultrasonic stimulation, wherein said time is decreased by about 25% or better relative to a bone implant not stimulated with said sonic or ultrasonic stimulation.

17. The method of claim 16 further comprising monitoring the ultrasonically-stimulated cell population by magnetic resonance microscopy to measure said osteogenesis.

18. The method of claim 1 wherein the biocompatible scaffold comprises an extracellular matrix protein, polyethylene glycol, agar, or collagen.

19. A method of accelerating osteogenesis comprising:

providing an isolated cell population capable of osteogenesis; and

exposing said cell population to a sonic or ultrasonic stimulation;

thereby accelerating osteogenesis of said cell population.

20. The method of claim 19, wherein said cell population comprises a bone cell obtained from mesenchymal stem cells exposed to a bone cell-differentiating signal.

21. The method of claim 19, wherein said sonic or ultrasonic exposure is in vitro, ex vivo, or both in vitro and ex vivo.

22. The method of claim 19 further comprising:

providing a biocompatible scaffold; and

introducing said cell population to said biocompatible scaffold.

23. The method of claim 22, wherein said exposure comprises an ultrasonic stimulation that is applied in a periodic manner, having a periodicity of about 24 hours, and repeated at least 5 times or more.

24. A method of implanting a cell or tissue implant into a patient in need of treatment comprising:

obtaining a transplantable cell population;

culturing said cell population in a culture media;

exposing said cell population to a sonic or ultrasonic stimulation, wherein said stimulation provides a capability for an enhanced implant outcome parameter; and

implanting said tissue implant having an enhanced implant outcome parameter to said patient.

25. The method of claim 24, further comprising:

providing a biocompatible scaffold; and

introducing said cell population to said scaffold.

26. The method of claim 24, wherein said transplantable cell population comprises mesenchymal stem cells.

27. The method of claim 26, wherein said cell population is obtained from said patient.

28. The method of claim 26, wherein at least a portion of said mesenchymal stem cells are exposed to a differentiating stimulation thereby generating differentiation of at least a portion of said mesenchymal stem cells to osteoblasts.