title: Local application of lactoferrin promotes bone regeneration in a rat critical-sized calvarial defect model as demonstrated by micro-CT and histological analysis.
abstract: Lactoferrin is a multifunctional glycoprotein with therapeutic potential for bone tissue engineering. The aim of this study was to assess the efficacy of local application of lactoferrin on bone regeneration. Five-millimetre critical-sized defects were created over the right parietal bone in 64 Sprague-Dawley rats. The rats were randomized into four groups: group 1 (n  =  20) had empty defects; group 2 (n  =  20) had defects grafted with collagen gels (3 mg/ml); group 3 (n  =  20) had defects grafted with collagen gels impregnated with bovine lactoferrin (10 μg/gel); and group 4 (n  =  4) had sham surgeries (skin and periosteal incisions only). The rats were sacrificed at 4 or 12 weeks post-operatively, and the calvaria were excised and evaluated with micro-CT (Skyscan 1172) followed by histology. The bone volume fraction (BV/TV) was higher in lactoferrin-treated animals at both timepoints, with groups 1, 2, 3 and 4 measuring 10.5  ±  1.1%, 8.6  ±  1.4%, 16.5  ±  0.6% and 24.27  ±  2.6%, respectively, at 4 weeks (P  <  0.05); and 12.2  ±  1.3%, 13.6  ±  1.5%, 21.9  ±  1.2% and 29.3  ±  0.8%, respectively, at 12 weeks (P  <  0.05). Histological analysis revealed that the newly formed bone within the calvarial defects of all groups was a mixture of woven and lamellar bone, with more bone in the group treated with lactoferrin at both timepoints. Our study demonstrated that local application of lactoferrin significantly increased bone regeneration in a rat critical-sized calvarial defect model. The profound effect of lactoferrin on bone regeneration has therapeutic potential to improve the poor clinical outcomes associated with bony non-union. LF In Vivo JTERM Authors Contributions. Copyright © 2016 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons, Ltd.
authors.affiliation: Bone and Joint Research Group, University of Auckland, Auckland, New Zealand.
authors.forename: Ryan
authors.initials: R
authors.lastname: Gao
authors.affiliation: Bone and Joint Research Group, University of Auckland, Auckland, New Zealand.
authors.forename: Maureen
authors.initials: M
authors.lastname: Watson
authors.affiliation: Bone and Joint Research Group, University of Auckland, Auckland, New Zealand.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Callon
authors.affiliation: Bone and Joint Research Group, University of Auckland, Auckland, New Zealand.
authors.forename: Donna
authors.initials: D
authors.lastname: Tuari
authors.affiliation: Waikato District Health Board, Waikato, New Zealand.
authors.forename: Michael
authors.initials: M
authors.lastname: Dray
authors.affiliation: Bone and Joint Research Group, University of Auckland, Auckland, New Zealand.
authors.forename: Dorit
authors.initials: D
authors.lastname: Naot
authors.affiliation: Department of Anatomy, University of Auckland, Auckland, New Zealand.
authors.forename: Satya
authors.initials: S
authors.lastname: Amirapu
authors.affiliation: Department of Surgery, Auckland District Health Board, Auckland, New Zealand.
authors.forename: Jacob T
authors.initials: JT
authors.lastname: Munro
authors.affiliation: Bone and Joint Research Group, University of Auckland, Auckland, New Zealand.
authors.forename: Jillian
authors.initials: J
authors.lastname: Cornish
authors.affiliation: Bone and Joint Research Group, University of Auckland, Auckland, New Zealand.
authors.forename: David S
authors.initials: DS
authors.lastname: Musson
mesh_terms: D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects*; D002417:Cattle; D004195:Disease Models, Animal; D007781:Lactoferrin / Q000494:pharmacology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D012886:Skull / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D055114:X-Ray Microtomography
chemical_list: D007781:Lactoferrin
keywords: bone healing; bone regeneration; calvarial defect; lactoferrin