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Local manganese chloride treatment accelerates fracture healing in a rat model
Author(s) -
Hreha Jeremy,
Wey Aaron,
Cunningham Catherine,
Krell Ethan S.,
Brietbart Eric A.,
Paglia David N.,
Montemurro Nicholas J.,
Nguyen Daniel A.,
Lee YungJae,
Komlos Daniel,
Lim Elisha,
Benevenia Joseph,
O'Connor J. Patrick,
Lin Sheldon S.
Publication year - 2015
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.22733
Subject(s) - bone healing , saline , immunohistochemistry , callus , chemistry , angiogenesis , medicine , manganese , rat model , endocrinology , surgery , biology , genetics , organic chemistry
ABSTRACT This study investigated the effects of local delivery of manganese chloride (MnCl 2 ), an insulin‐mimetic compound, upon fracture healing using a rat femoral fracture model. Mechanical testing, histomorphometry, and immunohistochemistry were performed to assess early and late parameters of fracture healing. At 4 weeks post‐fracture, maximum torque to failure was 70% higher ( P < 0.05) and maximum torsional rigidity increased 133% ( P < 0.05) in animals treated with 0.125 mg/kg MnCl 2 compared to saline controls. Histological analysis of the fracture callus revealed percent new mineralized tissue was 17% higher ( P < 0.05) at day 10. Immunohistochemical analysis of the 0.125 mg/kg MnCl 2 treated group, compared to saline controls, showed a 379% increase in the density of VEGF‐C+ cells. In addition, compared to saline controls, the 0.125 mg/kg MnCl 2 treated group showed a 233% and 150% increase in blood vessel density in the subperiosteal region at day 10 post‐fracture as assessed by detection of PECAM and smooth muscle α actin, respectively. The results suggest that local MnCl 2 treatment accelerates fracture healing by increasing mechanical parameters via a potential mechanism of amplified early angiogenesis leading to increased osteogenesis. Therefore, local administration of MnCl 2 is a potential therapeutic adjunct for fracture healing. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:122–130, 2015.