The effects of local vanadium treatment on angiogenesis and chondrogenesis during fracture healing.
This study quantified the effects of local intramedullary delivery of an organic vanadium salt, which may act as an insulin-mimetic on fracture healing. Using a BB Wistar rat femoral fracture model, local vanadyl acetylacetonate (VAC) was delivered to the fracture site and histomorphometry, mechanical testing, and immunohistochemistry were performed. Callus percent cartilage was 200% higher at day 7 (p < 0.05) and 88% higher at day 10 (p < 0.05) in the animals treated with 1.5 mg/kg of VAC. Callus percent mineralized tissue was 37% higher at day 14 (p < 0.05) and 31% higher at day 21 (p < 0.05) in the animals treated with 1.5 mg/kg of VAC. Maximum torque to failure was 104% and 154% higher at 4 weeks post-fracture (p < 0.05) for the healing femurs from the VAC-treated (1.5 and 3.0 mg/kg) animals. Animals treated with other VAC doses demonstrated increased mechanical parameters at 4 weeks (p < 0.05). Immunohistochemistry detected 62% more proliferating cells at days 7 (p < 0.05) and 94% more at day 10 (p < 0.05) in the animals treated with 1.5 mg/kg VAC. Results showed 100% more vascular endothelial growth factor-C (VEGF-C) positive cells and 80% more blood vessels at day 7 (p < 0.05) within the callus subperiosteal region of VAC-treated animals (1.5 mg/kg) compared to controls. The results suggest that local VAC treatment affects chondrogenesis and angiogenesis within the first 7-10 days post-fracture, which leads to enhanced mineralized tissue formation and accelerated fracture repair as early as 3-4 weeks post-fracture.
Department of Orthopaedics, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, 90 Bergen Street, Suite 7300, Newark, New Jersey 07103, USA. pagliada@umdnj.edu
David N
DN
Paglia
Aaron
A
Wey
Andrew G
AG
Park
Eric A
EA
Breitbart
Siddhant K
SK
Mehta
John D
JD
Bogden
Francis W
FW
Kemp
Joseph
J
Benevenia
J Patrick
JP
O'Connor
Sheldon S
SS
Lin
D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D049109:Cell Proliferation; D020219:Chondrogenesis / Q000187:drug effects*; D005264:Femoral Fractures / Q000628:therapy; D017102:Fracture Healing / Q000187:drug effects*; D006885:Hydroxybutyrates / Q000494:pharmacology*; D007150:Immunohistochemistry / Q000379:methods; D007328:Insulin / Q000378:metabolism; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010422:Pentanones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration; D013314:Stress, Mechanical; D019415:Torque; D014639:Vanadium / Q000494:pharmacology*
D006885:Hydroxybutyrates; D007328:Insulin; D010422:Pentanones; D014639:Vanadium; C049529:acetyl acetonate