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.