Effects of a Pasty Bone Cement Containing Brain-Derived Neurotrophic Factor-Functionalized Mesoporous Bioactive Glass Particles on Metaphyseal Healing in a New Murine Osteoporotic Fracture Model

Vivien Kauschke*, Maike Schneider, Annika Jauch, Matthias Schumacher, Marian Kampschulte, Marcus Rohnke, Anja Henss, Coralie Bamberg, Katja Trinkaus, Michael Gelinsky, Christian Heiss, Katrin Susanne Lips

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

21 Citations (Web of Science)

Abstract

The development of new and better implant materials adapted to osteoporotic bone is still urgently required. Therefore, osteoporotic muscarinic acetylcholine receptor M3 (M3 mAChR) knockout (KO) and corresponding wild type (WT) mice underwent osteotomy in the distal femoral metaphysis. Fracture gaps were filled with a pasty -tricalcium phosphate (-TCP)-based hydroxyapatite (HA)-forming bone cement containing mesoporous bioactive CaP-SiO2 glass particles (cement/MBG composite) with or without Brain-Derived Neurotrophic Factor (BDNF) and healing was analyzed after 35 days. Histologically, bone formation was significantly increased in WT mice that received the BDNF-functionalized cement/MBG composite compared to control WT mice without BDNF. Cement/MBG composite without BDNF increased bone formation in M3 mAChR KO mice compared to equally treated WT mice. Mass spectrometric imaging showed that the BDNF-functionalized cement/MBG composite implanted in M3 mAChR KO mice was infiltrated by newly formed tissue. Leukocyte numbers were significantly lower in M3 mAChR KO mice treated with BDNF-functionalized cement/MBG composite compared to controls without BDNF. C-reactive protein (CRP) concentrations were significantly lower in M3 mAChR KO mice that received the cement/MBG composite without BDNF when compared to WT mice treated the same. Whereas alkaline phosphatase (ALP) concentrations in callus were significantly increased in M3 mAChR KO mice, ALP activity was significantly higher in WT mice. Due to a stronger effect of BDNF in non osteoporotic mice, higher BDNF concentrations might be needed for osteoporotic fracture healing. Nevertheless, the BDNF-functionalized cement/MBG composite promoted fracture healing in non osteoporotic bone.
Original languageEnglish
Article number3531
Number of pages19
JournalInternational journal of molecular sciences
Volume19
Issue number11
DOIs
Publication statusPublished - 1 Nov 2018

Keywords

  • osteoporosis
  • metaphyseal fracture healing model
  • -TCP-based HA-forming bone cement
  • mesoporous bioactive glass
  • BDNF
  • CALCIUM-PHOSPHATE CEMENT
  • DRUG-DELIVERY
  • OSTEOGENIC DIFFERENTIATION
  • GROWTH-FACTOR
  • STEM-CELLS
  • RECEPTOR
  • DEFECT
  • COMPOSITES
  • OSTEOBLAST
  • OSTEOTOMY

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