Methods for modulating osteochondral development using bioelectrical stimulation
First Claim
1. A kit for preparing a tissue suitable for transplantation, the kit comprising:
- cells; and
an electrical stimulator providing an electrical stimulus waveform that includes a number of consecutive D-type signal pulse bursts that repeat at a fixed interval of 1 second or longer between consecutive pulse bursts;
wherein each of the number of consecutive D-type signal pulse bursts includes a D-type signal having a frequency of less than 910 Hz, a shorter negative voltage pulse length of between 100 microseconds (μ
sec) and 1000 μ
sec in duration, a longer positive voltage pulse length in excess of 1 millisecond in duration, and a pulse burst length of from about 100 milliseconds to about 1 second; and
wherein the electrical stimulus waveform promotes proliferation, differentiation, or matrix production of the cells into a tissue suitable for transplantation.
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Abstract
Compositions and methods are provided for modulating the growth, development and repair of bone, cartilage or other connective tissue. Devices and stimulus waveforms are provided to differentially modulate the behavior of osteoblasts, chondrocytes and other connective tissue cells to promote proliferation, differentiation, matrix formation or mineralization for in vitro or in vivo applications. Continuous-mode and pulse-burst-mode stimulation of cells with charge-balanced signals may be used. Bone, cartilage and other connective tissue growth is stimulated in part by nitric oxide release through electrical stimulation and may be modulated through co-administration of NO donors and NO synthase inhibitors. Bone, cartilage and other connective tissue growth is stimulated in part by release of BMP-2 and BMP-7 in response to electrical stimulation to promote differentiation of cells. The methods and devices described are useful in promoting repair of bone fractures, cartilage and connective tissue repair as well as for engineering tissue for transplantation.
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Citations
7 Claims
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1. A kit for preparing a tissue suitable for transplantation, the kit comprising:
-
cells; and an electrical stimulator providing an electrical stimulus waveform that includes a number of consecutive D-type signal pulse bursts that repeat at a fixed interval of 1 second or longer between consecutive pulse bursts; wherein each of the number of consecutive D-type signal pulse bursts includes a D-type signal having a frequency of less than 910 Hz, a shorter negative voltage pulse length of between 100 microseconds (μ
sec) and 1000 μ
sec in duration, a longer positive voltage pulse length in excess of 1 millisecond in duration, and a pulse burst length of from about 100 milliseconds to about 1 second; andwherein the electrical stimulus waveform promotes proliferation, differentiation, or matrix production of the cells into a tissue suitable for transplantation. - View Dependent Claims (2, 3, 4, 5, 6, 7)
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Specification