Bone morphogenetic protein-2 and pulsed electrical stimulation synergistically promoted osteogenic differentiation on MC-3T3-E1 cells.

Electrical stimulation (ES) plays an important role in regulating cell osteoblast differentiation. As a noninvasive rehabilitation therapy method, Es has a unique role in postoperative recovery. Bone morphogenetic protein-2 (BMP-2) is the most commonly used bioactive molecule in in situ tissue engineering scaffolds, and it plays an important regulatory role in the whole process of bone injury repair. In this study, the osteogenic regulation of MC-3T3-E1 cells was studied by combining pulsed electrical stimulation (PES) and different concentrations of BMP-2. The results showed that PES and BMP-2 could synergically promote the proliferation of MC-3T3-E1 cells. The qPCR results of osteoblast-related genes showed that PES was synergistic with BMP-2 to promote osteoblast differentiation mainly through the regulation of the Smad/BMP and insulin like growth factor 1 (IGF1) signaling pathways. The expression level of alkaline phosphatase (ALP) and alizarin red staining further demonstrated the synergistic effect of PES and BMP-2 on promoting osteogenic differentiation and mineralization of cells. PES and BMP-2 could also synergically promote cell proliferation, expression of collagen I (COL-I) and ALP, and cell mineralization on the 3D-printed polylactic acid scaffold. These results suggest that the use of PES can enhance the osteogenic effect of in situ bone repair scaffolds containing BMP-2, reduce the dose of BMP-2 alone, and reduce the possible side effects of high-dose BMP-2 in vivo.

PLGA/BGP/Nef porous composite restrains osteoclasts by inhibiting the NF-κB pathway, enhances IGF-1-mediated osteogenic differentiation and promotes bone regeneration.

BACKGROUND: Novel bone substitutes are urgently needed in experimental research and clinical orthopaedic applications. There are many traditional Chinese medicines that have effects on bone repair. However, application of natural medicines in traditional Chinese medicine to bone tissue engineering and its mechanism were rarely reported. RESULTS: In this study, the osteogenic ability of bioactive glass particles (BGPs) and the osteogenic and osteoclastic ability of neferine (Nef) were fused into PLGA-based bone tissue engineering materials for bone regeneration. BGPs were prepared by spray drying and calcination. Particles and Nef were then mixed with PLGA solution to prepare porous composites by the phase conversion method. Here we showed that Nef inhibited proliferation and enhanced ALP activity of MC3T3-E1 cells in a dose- and time-dependent manner. And the composites containing Nef could also inhibit RANKL-induced osteoclast formation (p < 0.05). Mechanistically, the PLGA/BGP/Nef composite downregulated the expression of NFATC1 by inhibiting the NF-κB pathway to restrain osteoclasts. In the other hands, PLGA/BGP/Nef composite was first demonstrated to effectively activate the IGF-1R/PI3K/AKT/mTOR pathway to enhance IGF-1-mediated osteogenic differentiation. The results of animal experiments show that the material can effectively promote the formation and maturation of new bone in the skull defect site. CONCLUSIONS: The PLGA/BGP/Nef porous composite can restrain osteoclasts by inhibiting the NF-κB pathway, enhance IGF-1-mediated osteogenic differentiation and promotes bone regeneration, and has the potential for clinical application.

Sustained Delivery of Methylsulfonylmethane from Biodegradable Scaffolds Enhances Efficient Bone Regeneration.

Introduction: As a popular dietary supplement containing sulfur compound, methylsulfonylmethane (MSM) has been widely used as an alternative oral medicine to relieve joint pain, reduce inflammation and promote collagen protein synthesis. However, it is rarely used in developing bioactive scaffolds in bone tissue engineering. Methods: Three-dimensional (3D) hydroxyapatite/poly (lactide-co-glycolide) (HA/PLGA) porous scaffolds with different doping levels of MSM were prepared using the phase separation method. MSM loading efficiency, in vitro drug release as well as the biological activity of MSM-loaded scaffolds were investigated by incubating mouse pre-osteoblasts (MC3T3-E1) in the uniform and interconnected porous scaffolds. Results: Sustained release of MSM from the scaffolds was observed, and the total MSM release from 1% and 10% MSM/HA/PLGA scaffolds within 16 days was up to 64.9% and 68.2%, respectively. Cell viability, proliferation, and alkaline phosphatase (ALP) activity were significantly promoted by incorporating 0.1% of MSM in the scaffolds. In vivo bone formation ability was significantly enhanced for 1% MSM/HA/PLGA scaffolds indicated by the repair of rabbit radius defects which might be affected by a stimulated release of MSM by enzyme systems in vivo. Discussion: Finding from this study revealed that the incorporation of MSM would be effective in improving the osteogenesis activity of the HA/PLGA porous scaffolds.

In Vivo MRI and X-Ray Bifunctional Imaging of Polymeric Composite Supplemented with GdPO4 ·H2 O Nanobundles for Tracing Bone Implant and Bone Regeneration.

Homogeneous and monodisperse GdPO4 ·H2 O nanobundles are successfully synthesized via a solvothermal method. Then, GdPO4 ·H2 O are incorporated into the composite of hydroxyapatite and poly(lactic-co-glycolic acid) to obtain a biodegradable and traceable bone implant. After implanted, the GdPO4 ·H2 O/HA/PLGA implant and the newly formed bone can be easily traced and observed through the combination of magnetic resonance imaging and X-ray imaging.