Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR018033-13
Application #
3154963
Study Section
Orthopedics and Musculoskeletal Study Section (ORTH)
Project Start
1978-12-01
Project End
1987-07-31
Budget Start
1986-08-01
Budget End
1987-07-31
Support Year
13
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

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
Brighton, C T; Hunt, R M (1997) Early histologic and ultrastructural changes in microvessels of periosteal callus. J Orthop Trauma 11:244-53
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
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

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