3D-printed Mg-1Ca/polycaprolactone composite scaffolds with promoted bone regeneration

In bone tissue engineering,polycaprolactone(PCL)is a promising material with good biocompatibility,but its poor degradation rate,mechanical strength,and osteogenic properties limit its application.In this study,we developed an Mg-1Ca/polycaprolactone(Mg-1Ca/PCL)composite scaffolds to overcome these limitations.We used a melt blending method to prepare Mg-1Ca/PCL composites with Mg-1Ca alloy powder mass ratios of 5,10,and 20 wt%.Porous scaffolds with controlled macro-and microstructure were printed using the fused deposition modeling method.We explored the mechanical strength,biocompatibility,osteogenesis performance,and molecular mechanism of the Mg-1Ca/PCL composites.The 5 and 10 wt%Mg-1Ca/PCL composites were found to have good biocompatibility.Moreover,they promoted the mechanical strength,proliferation,adhesion,and osteogenic differentiation of human bone marrow stem cells(hBMSCs)of pure PCL.In vitro degradation experiments revealed that the composite material stably released Mg_(2)+ions for a long period;it formed an apatite layer on the surface of the scaffold that facilitated cell adhesion and growth.Microcomputed tomography and histological analysis showed that both 5 and 10 wt%Mg-1Ca/PCL composite scaffolds promoted bone regeneration bone defects.Our results indicated that the Wnt/β-catenin pathway was involved in the osteogenic effect.Therefore,Mg-1Ca/PCL composite scaffolds are expected to be a promising bone regeneration material for clinical application.Statement of significance:Bone tissue engineering scaffolds have promising applications in the regeneration of critical-sized bone defects.However,there remain many limitations in the materials and manufacturing methods used to fabricate scaffolds.This study shows that the developed Ma-1Ca/PCL composites provides scaffolds with suitable degradation rates and enhanced boneformation capabilities.Furthermore,the fused deposition modeling method allows precise control of the macroscopic morphology and microscopic porosity of the scaffold.The obtained porous scaffolds can significantly promote the regeneration of bone defects.

Platelet factor 4 induces bone loss by inhibiting the integrinα5-FAK-ERK pathway

Background:The effect of platelet factor 4(PF4)on bone marrow mesenchymal stem cells(BMMSCs)and osteoporosis is poorly understood.Therefore,this study aimed to evaluate the effects of PF4-triggered bone destruction in mice and determine the underlying mechanism.Methods:First,in vitro cell proliferation and cell cycle of BMMSCs were assessed using a CCK8 assay and flow cytometry,respectively.Osteogenic differentiation was confirmed using staining and quantification of alkaline phosphatase and Alizarin Red S.Next,an osteoporotic mouse model was established by performing bilateral ovariectomy(OVX).Furthermore,the PF4 concentrations were obtained using enzymelinked immunosorbent assay.The bone microarchitecture of the femur was evaluated using microCT and histological analyses.Finally,the key regulators of osteogenesis and pathways were investigated using quantitative real-time polymerase chain reaction and Western blotting.Results:Human PF4 widely and moderately decreased the cell proliferation and osteogenic differentiation ability of BMMSCs.Furthermore,the levels of PF4 in the serum and bone marrow were generally increased,whereas bone microarchitecture deteriorated due to OVX.Moreover,in vivo mouse PF4 supplementation triggered bone deterioration of the femur.In addition,several key regulators of osteogenesis were downregulated,and the integrinα5-focal adhesion kinase-extracellular signalregulated kinase(ITGA5-FAK-ERK)pathway was inhibited due to PF4 supplementation.Conclusions:PF4 may be attributed to OVX-i nduced bone loss triggered by the suppression of bone formation in vivo and alleviate BMMSC osteogenic differentiation by inhibiting the ITGA5-FAK-ERK pathway.

Photocrosslinkable Col/PCL/Mg composite membrane providing spatiotemporal maintenance and positive osteogenetic effects during guided bone regeneration

Guided bone regeneration membranes have been effectively applied in oral implantology to repair bone defects.However,typical resorbable membranes composed of collagen(Col)have insufficient mechanical properties and high degradation rate,while non-resorbable membranes need secondary surgery.Herein,we designed a photocrosslinkable collagen/polycaprolactone methacryloyl/magnesium(Col/PCLMA/Mg)composite membrane that provided spatiotemporal support effect after photocrosslinking.Magnesium particles were added to the PCLMA solution and Col/PCLMA and Col/PCLMA/Mg membranes were developed;Col membranes and PCL membranes were used as controls.After photocrosslinking,an interpenetrating polymer network was observed by scanning electron microscopy(SEM)in Col/PCL and Col/PCL/Mg membranes.The elastic modulus,swelling behavior,cytotoxicity,cell attachment,and cell proliferation of the membranes were evaluated.Degradation behavior in vivo and in vitro was monitored according to mass change and by SEM.The membranes were implanted into calvarial bone defects of rats for 8 weeks.The Col/PCL and Col/PCL/Mg membranes displayed much higher elastic modulus(p<0.05),and a lower swelling rate(p<0.05),than Col membranes,and there were no differences in cell biocompatibility among groups(p>0.05).The Col/PCL and Col/PCL/Mg membranes had lower degradation rates than the Col membranes,both in vivo and in vitro(p<0.05).The Col/PCL/Mg groups showed enhanced osteogenic capability compared with the Col groups at week 8(p<0.05).The Col/PCL/Mg composite membrane represents a new strategy to display space maintenance and enhance osteogenic potential,which meets clinical needs.