The object of the proposed research is to continue to investigate the stimulation of fracture healing with a capacitively coupled electrical field and to determine the mechanisms of action of electrically induced osteogenesis. The proposed research is designed 1) to determine the most efficient duty cycle in applying a capacitively coupled electrical signal to stimulate fracture healing in are osteotomized rabbit fibula model, and 2) to determine the mechanism(s) fo electrically induced osteogenesis by evaluating a) the microenvironmental changes (p0/2, pH) occurring in the vicinity of a cathode, b) possible responding cells (bone cell, capillary endothelial cell, pericyte, and polymorphic cells), and c) intracellular calcium, cyclic AMP, and prostaglanin (PGE2). Methods to be used include histologic, roentgenographic, and mechanical testing of osteotomized rabbit fibula; mathematic modeling using finite element analysis to calculate electric fields in rabbit fibula callus; microscopic morphologic digitablization (Zeiss MOP-3) of newly formed bone in the vicinity of a cathode in the rabbit tibial medullary canal; needle electrode determination of p0/2 and pH of medullary canal in the vicinity of an active cathode; Coulter cell counting, S35 and C14proline uptake, and collagen typing of isolated rat calvarial bone cells, calf brain capillary endothelial cells and pericytes, and rabbit tibia post-traumatic polymorphic cells exposed to various capacitively coupled electrical fields; histologic examination and collagen content and typing of bone cells, endothelial cells, pericytes, and polymorphics grown in Algire diffusion chambers placed within the rabbit tibia medullary canal and exposed to direct current; electron microscopic evaluation of the role of the polymorphic cell as an osteoblast precursor cell and of the role of the endothelial cell and pericyte as possible origins of the polymorphic cell and correlating these findings with histologic staining for factor VIII, antismooth muscle actin antibody, and for alkaline phosphatase; cAMP, prostaglandin, and intracellular ionized calcium changes induced by an electric field; and Fura 2 fluorescence and quantitative digitized fluorescent microscopy to determine the relationship of chondrocyte intracellular calcium to matrix mineralization in the fracture callus.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Method to Extend Research in Time (MERIT) Award (R37)
Project #
Application #
Study Section
Special Emphasis Panel (NSS)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Pennsylvania
Schools of Medicine
United States
Zip Code
Allen, F D; Hung, C T; Pollack, S R et al. (2000) Serum modulates the intracellular calcium response of primary cultured bone cells to shear flow. J Biomech 33:1585-91
Lorich, D G; Brighton, C T; Gupta, R et al. (1998) Biochemical pathway mediating the response of bone cells to capacitive coupling. Clin Orthop Relat Res :246-56
Reilly, T M; Seldes, R; Luchetti, W et al. (1998) Similarities in the phenotypic expression of pericytes and bone cells. Clin Orthop Relat Res :95-103
Zhuang, H; Wang, W; Seldes, R M et al. (1997) Electrical stimulation induces the level of TGF-beta1 mRNA in osteoblastic cells by a mechanism involving calcium/calmodulin pathway. Biochem Biophys Res Commun 237:225-9
Wang, W; Zhuang, H; Levitz, C L et al. (1997) The increased level of PDGF-A contributes to the increased proliferation induced by mechanical stimulation in osteoblastic cells. Biochem Mol Biol Int 43:339-46
Brighton, C T; Hunt, R M (1997) Early histologic and ultrastructural changes in microvessels of periosteal callus. J Orthop Trauma 11:244-53
Hung, C T; Allen, F D; Pollack, S R et al. (1996) What is the role of the convective current density in the real-time calcium response of cultured bone cells to fluid flow? J Biomech 29:1403-9
Brighton, C T; Fisher Jr, J R; Levine, S E et al. (1996) The biochemical pathway mediating the proliferative response of bone cells to a mechanical stimulus. J Bone Joint Surg Am 78:1337-47
Zhuang, H; Wang, W; Tahernia, A D et al. (1996) Mechanical strain-induced proliferation of osteoblastic cells parallels increased TGF-beta 1 mRNA. Biochem Biophys Res Commun 229:449-53
Hung, C T; Allen, F D; Pollack, S R et al. (1996) Intracellular Ca2+ stores and extracellular Ca2+ are required in the real-time Ca2+ response of bone cells experiencing fluid flow. J Biomech 29:1411-7

Showing the most recent 10 out of 19 publications