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

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.

BDNF promoted osteoblast migration and fracture healing by up‐regulating integrin β1 via TrkB‐mediated ERK1/2 and AKT signalling

“…29 Afterwards, Kilian revealed that BDNF and TrkB also existed in human callus in 2014 and some clinical or experimental researches all gradually confirmed that BDNF played a positive role in accelerating bone union. [4][5][6][7][8] However, there is little study in illustrating its mechanism. Considering the putative effects on cell migration, our study proved that BDNF/TrkB could promote osteoblasts migration for the first time.…”

Functionalization of Ceramic Coatings for Enhancing Integration in Osteoporotic Bone: A Systematic Review

“…Kauschke et al [21] created a genetic model of OP to investigate the effect on bone regeneration of α-tricalcium phosphate (α-TCP)-based hydroxyapatite (HA) containing bioactive CaP-silicon dioxide (SiO 2 ) glass particles with or without BDNF functionalization. The outcomes of implantation in the distal femoral metaphyseal gap highlighted a greater regenerative potential in the healthy group than in OP ones.…”

Effects of BDNF and PEC Nanoparticles on Osteocytes

“…The addition of BDNF to monocyte cultures during differentiation into osteoclasts did neither impair the osteoclastogenesis nor the activity of osteoclasts if they were harvested from healthy donors [ 16 , 17 ]. In non-tumorigenic animal models, e.g., in murine and rat fracture models, the application of BDNF revealed enhanced bone formation and fracture healing [ 18 , 19 ]. The positive effect of BDNF on fracture healing was also determined when BDNF was released from a bone substitute material [ 18 ].…”

“…In non-tumorigenic animal models, e.g., in murine and rat fracture models, the application of BDNF revealed enhanced bone formation and fracture healing [ 18 , 19 ]. The positive effect of BDNF on fracture healing was also determined when BDNF was released from a bone substitute material [ 18 ]. To refine the release of BDNF by bone substitute materials like calcium phosphate cements, it would be promising to couple BDNF to a drug delivery system.…”