title: Metaphyseal bone formation induced by a new injectable β-TCP-based bone substitute: a controlled study in rabbits.
abstract: OBJECTIVE
  Adequate filling of bone defects still poses a challenge in every day clinical work. As many bone defects are irregularly shaped the need for appropriate scaffolds reaching the complete defect surface are great. The purpose of this pre-clinical pilot study was to investigate the handling, biocompatibility, biodegradation and osteoconductivity of a new pasty bone substitute (pure phase β-TCP, hyaluronic acid, methylcellulose) in bone tissue.
  
  
  METHODS
  In an unilateral tibial defect model the peri-implant and bone tissue response to the new pasty bone substitute was tested in New Zealand white rabbits for up to 24 weeks compared to empty controls. Analysis included HR-pQCT scans, histomorphometric evaluation and quantification of vascularization of un-decalcified histological slices.
  
  
  RESULTS
  After 1 week the experimental group presented significantly higher new bone volume fraction (p = 0.021) primarily consisting of immature bone matrix and higher vessel density compared to controls (p = 0.013). After 4 weeks bone formation was not significantly different to controls but was distributed more evenly throughout the defect. Bone matrix was now mineralized and trabeculae were thicker than in controls (p = 0.002) indicating faster intramedullary bone maturation. Controls presented extensive periosteal bone formation, major fibrous tissue influx and high vascularization. After 12 and 24 weeks there was no new bone detectable. There were no severe signs of inflammation at all time points.
  
  
  CONCLUSIONS
  The substitute showed an early induction of bone formation. It promoted accelerated intramedullary bone repair and maturation and prevented periosteal bone formation indicating its potential use for reconstructive surgery of bone defects.
authors.affiliation: 1Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Krause
authors.forename: Ralf
authors.initials: R
authors.lastname: Oheim
authors.forename: Philip
authors.initials: P
authors.lastname: Catala-Lehnen
authors.forename: Jan M
authors.initials: JM
authors.lastname: Pestka
authors.forename: Christiane
authors.initials: C
authors.lastname: Hoffmann
authors.forename: Wolf
authors.initials: W
authors.lastname: Huebner
authors.forename: Fabian
authors.initials: F
authors.lastname: Peters
authors.forename: Florian
authors.initials: F
authors.lastname: Barvencik
authors.forename: Michael
authors.initials: M
authors.lastname: Amling
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D001846:Bone Development; D018786:Bone Substitutes; D002130:Calcium Phosphates / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D011817:Rabbits
chemical_list: D001672:Biocompatible Materials; D018786:Bone Substitutes; D002130:Calcium Phosphates; C485817:beta-tricalcium phosphate
keywords: bone substitute; hyaluronic acid; methylcellulose; tibial defect model; β-TCP