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

doi:10.3390/ijms19113531

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 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.

Highlights

Physiological bone undergoes constant remodeling which is a balanced process accomplished by bone forming osteoblasts and bone resorbing osteoclasts
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 with or without Brain-Derived Neurotrophic Factor (BDNF) and healing was analyzed after 35 days
Alkaline phosphatase (Alp), cathepsin K (Ctsk) and connexin 43 (Cx43) mRNAs were expressed at the bone tissue implant interface in femurs of M3 mAChR KO and wild type (WT) mice

Summary

Introduction

Physiological bone undergoes constant remodeling which is a balanced process accomplished by bone forming osteoblasts and bone resorbing osteoclasts. In osteoporosis this balance is disturbed in favor of osteoclastic bone resorption. Consequences are low bone mineral density and diminished bone microarchitecture often leading to fractures [1]. Osteoporotic fractures are a severe health problem worldwide with 8.9 million cases every year [1]. Predominant osteoporotic fracture sites are vertebrae, proximal femurs, proximal humeri and distal radii [2]. The second common fracture site in elderly people is the distal femur [3]

Methods

Discussion

Conclusion