The object of the proposed research is to continue investigating the effects of applied electrical fields on the acceleration of fracture healing in laboratory animals. The proposed research is designed (1) to determine the optimum parameters of applied (exogenous) electricity for accelerating fracture healing, (2) to determine the role of stress generated (endogenous) electricity in fracture healing, and (3) to determine the mechanism of electrically induced osteogenesis at the cell level. Methods to be used include the comparison of the osteogenic response of in vitro fetal rat tibia and in vivo healing rabbit fibula to constant direct current, various pulsed unidirectional electric fields, and various electromagnetic fields. Osteogenesis and bone healing will be evaluated by incorporation of tritiated thymidine, Ca45, and 35SO4 as well as maximum resistance to bending as determined by an Instron Testing Machine. Stress generated potentials will be measured in fracture calluses. Origin of stress generated potentials will be evaluated by altering collagen in tendon biochemically. The mechanism of action of electrically induced osteogenesis will be sought by determining (1) pO2 and pH changes in the vicinity of a cathode, (2) changes in surface of cell membrane, (3) mitochondria release of calcium, (4) cellular proliferation and migration, and (5) collagen and proteoglycan biosynthesis and processing.

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National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
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Orthopedics and Musculoskeletal Study Section (ORTH)
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University of Pennsylvania
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Brighton, C T; Lorich, D G; Kupcha, R et al. (1992) The pericyte as a possible osteoblast progenitor cell. Clin Orthop Relat Res :287-99
Deren, J A; Kaplan, F S; Brighton, C T (1990) Alkaline phosphatase production by periosteal cells at various oxygen tensions in vitro. Clin Orthop Relat Res :307-12
Friedenberg, Z B; Brighton, C T; Michelson, J D et al. (1989) The effects of demineralized bone matrix and direct current on an ""in vivo"" culture of bone marrow cells. J Orthop Res 7:22-7
Brighton, C T; McCluskey, W P (1988) Response of cultured bone cells to a capacitively coupled electric field: inhibition of cAMP response to parathyroid hormone. J Orthop Res 6:567-71
Rubinacci, A; Black, J; Brighton, C T et al. (1988) Changes in bioelectric potentials on bone associated with direct current stimulation of osteogenesis. J Orthop Res 6:335-45
Brighton, C T; Hunt, R M (1986) Histochemical localization of calcium in the fracture callus with potassium pyroantimonate. Possible role of chondrocyte mitochondrial calcium in callus calcification. J Bone Joint Surg Am 68:703-15
Brighton, C T; Hunt, R M (1986) Ultrastructure of electrically induced osteogenesis in the rabbit medullary canal. J Orthop Res 4:27-36
Esterhai Jr, J L; Brighton, C T; Heppenstall, R B et al. (1986) Nonunion of the humerus. Clinical, roentgenographic, scintigraphic, and response characteristics to treatment with constant direct current stimulation of osteogenesis. Clin Orthop Relat Res :228-34
Esterhai, J L; Friedenberg, Z B; Brighton, C T et al. (1985) Temporal course of bone formation in response to constant direct current stimulation. J Orthop Res 3:137-9
Dymecki, S M; Black, J; Nord, D S et al. (1985) Medullary osteogenesis with platinum cathodes. J Orthop Res 3:125-36

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