Compositions and methods are provided for modulating the growth,
development and repair of cartilage, bone or other connective tissue.
Devices and stimulus waveforms are provided to differentially modulate
the behavior of chondrocytes, osteoblasts 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. Cartilage, bone 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. 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.