Device and method for bioelectric stimulation accelerating bone integration into implant healing

A method of accelerating the healing of an implant in a subject, the method comprising:

• applying to the implant a bioelectric signal selected from the group consisting of a biphasic pulse of between 2,000 Hz and 750,000 Hz and a biphasic pulse of about 3,000,000 Hz, with a voltage of between 0.001 volts and 4 volts, and
• stimulating the implant by applying a bioelectric signal to the implant to upregulate expression of bone morphogenic protein 9 (BMP9), wherein the bioelectric signal is a biphasic pulse of between 100 Hz and 300 Hz with a voltage of between 0.1 volts and 4 volts as measured at the cellular level,
• so as to promote bone osteointegration of the implant.

A method of treating a cell, the method comprising:

• stimulating the cell to modulate expression of hypoxia-inducible factor 1-alpha (“HIF1α”) by the cell by applying a bioelectric signal to the cell, wherein the bioelectric signal is selected from the group consisting of 0.25 mA to 0.75 mA (3.0 V), 80 to 100 Hz, 80 to 110 μs pulse width, square wave and 30 Hz, 3.5 mV, with the voltage measured at the cell.

A method of accelerating the healing of a bone graft in a subject, the method comprising:

• applying to the bone graft and cellular tissue surrounding the bone graft a bioelectric signal selected from the group consisting of a biphasic pulse of between 2,000 Hz and 750,000 Hz and a biphasic pulse of about 3,000,000 Hz, with a voltage of between 0.001 volts and 4 volts, and
• stimulating the implant by applying a bioelectric signal to the implant to upregulate expression of bone morphogenic protein 9 (BMP9), wherein the bioelectric signal is a biphasic pulse of between 100 Hz and 300 Hz with a voltage of between 0.1 volts and 4 volts as measured at the cellular level.

A method of treating a cell, the method comprising:

• stimulating the cell to upregulate expression of osteoprotegerin (OPG) by the cell by applying a bioelectric signal to the cell, wherein the bioelectric signal is selected from the group consisting of a biphasic pulse of between 2,500 Hz and 750,000 Hz and a biphasic pulse of about 3,000,000 Hz, with a voltage of between 0.001 volts and 4 volts as measured at the cell.

A method of treating a cell, the method comprising:

• stimulating the cell to downregulate expression of osteoprotegerin by the cell by applying a bioelectric signal to the cell, wherein the bioelectric signal is selected from the group consisting of a biphasic pulse of between 100 Hz and 1,000 Hz and a biphasic pulse of about 1,000,000 Hz, with a voltage of between 0.001 volts and 4 volts as measured at the cell.

A method of treating a cell, the method comprising:

• stimulating the cell to upregulate expression of transforming growth factor beta 1 (TGF-β1) by the cell by applying a bioelectric signal to the cell, wherein the bioelectric signal is a square, biphasic waveform at 50% duty, wherein the frequency is at least 75 Hz and the signal amplitude is about 1.0 V as measured at the cell.