1. Effects of local insulin delivery on subperiosteal angiogenesis and mineralized tissue formation during fracture healing.
- Author
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Paglia DN, Wey A, Breitbart EA, Faiwiszewski J, Mehta SK, Al-Zube L, Vaidya S, Cottrell JA, Graves D, Benevenia J, O'Connor JP, and Lin SS
- Subjects
- Animals, Biomechanical Phenomena drug effects, Biomechanical Phenomena physiology, Blood Vessels metabolism, Calcification, Physiologic physiology, Cell Proliferation drug effects, Diaphyses diagnostic imaging, Diaphyses drug effects, Diaphyses physiology, Disease Models, Animal, Female, Femoral Fractures diagnostic imaging, Femoral Fractures physiopathology, Femur diagnostic imaging, Femur drug effects, Femur physiology, Fracture Healing physiology, Hypoglycemic Agents pharmacology, Injections, Intralesional, Male, Neovascularization, Physiologic physiology, Platelet Endothelial Cell Adhesion Molecule-1 metabolism, Radiography, Random Allocation, Rats, Rats, Inbred BB, Vascular Endothelial Growth Factor A metabolism, Calcification, Physiologic drug effects, Femoral Fractures drug therapy, Fracture Healing drug effects, Insulin, Ultralente pharmacology, Neovascularization, Physiologic drug effects
- Abstract
Local insulin delivery has been shown to improve osseous healing in diabetic animals. The purpose of this study was to quantify the effects of local intramedullary delivery of saline or Ultralente insulin (UL) on various fracture healing parameters using an in vivo non-diabetic BB Wistar rat model. Quantitation of local insulin levels showed a rapid release of insulin from the fractured femora, demonstrating complete release at 2 days. RT-PCR analysis revealed that the expression of early osteogenic markers (Col1α2, osteopontin) was significantly enhanced with UL treatment when compared with saline controls (p < 0.05). Significant differences in VEGF + cells and vascularity were evident between the treatment and control groups at day 7 (p < 0.05). At day 21, histomorphometric analysis demonstrated a significant increase in percent mineralized tissue in the UL-treated animals compared with controls (p < 0.05), particularly within the subperiosteal region of the fracture callus. Mechanical testing at 4 weeks showed significantly greater mechanical strength for UL-treated animals (p < 0.05), but healing in control animals caught up at 6 weeks post-fracture. These results suggest that the primary osteogenic effect of UL during the early stages of fracture healing (1-3 weeks) is through an increase in osteogenic gene expression, subperiosteal angiogenesis, and mineralized tissue formation., (Copyright © 2012 Orthopaedic Research Society.)
- Published
- 2013
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