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Int. J. Mol. Sci. 2018, 19(11), 3531; https://doi.org/10.3390/ijms19113531

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

1
Experimental Trauma Surgery, Justus-Liebig-University Giessen, Aulweg 128, 35392 Giessen, Germany
2
Centre for Translational Bone, Joint and Soft Tissue Research, Medical Faculty and University Hospital, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany
3
Currently at MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, 6200 MD Maastricht, The Netherlands
4
Department of Radiology, University Hospital of Giessen-Marburg, Campus Giessen Klinikstrasse 33, 35392 Giessen, Germany
5
Institute of Physical Chemistry and Center for Materials Research, Justus-Liebig-University Giessen, Heinrich-Buff-Ring 17, 35392 Giessen, Germany
6
Department of Trauma, Hand and Reconstructive Surgery, University Hospital of Giessen-Marburg, Campus: Giessen, Rudolf-Buchheimstrasse 7, 35392 Giessen, Germany
*
Author to whom correspondence should be addressed.
Received: 6 October 2018 / Revised: 29 October 2018 / Accepted: 5 November 2018 / Published: 9 November 2018
(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering)
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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 α-tricalcium phosphate (α-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 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. View Full-Text
Keywords: osteoporosis; metaphyseal fracture healing model; α-TCP-based HA-forming bone cement; mesoporous bioactive glass; BDNF osteoporosis; metaphyseal fracture healing model; α-TCP-based HA-forming bone cement; mesoporous bioactive glass; BDNF
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Kauschke, V.; Schneider, M.; Jauch, A.; Schumacher, M.; Kampschulte, M.; Rohnke, M.; Henss, A.; Bamberg, C.; Trinkaus, K.; Gelinsky, M.; Heiss, C.; Lips, K.S. 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. Int. J. Mol. Sci. 2018, 19, 3531.

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