Vascularized bone regeneration accelerated by 3D-printed nanosilicate-functionalized polycaprolactone scaffold

Critical oral-maxillofacial bone defects,damaged by trauma and tumors,not only affect the physiological functions and mental health of patients but are also highly challenging to reconstruct.Personalized biomaterials customized by 3D printing technology have the potential to match oralmaxillofacial bone repair and regeneration requirements.Laponite(LAP)nanosilicates have been added to biomaterials to achieve biofunctional modification owing to their excellent biocompatibility and bioactivity.Herein,porous nanosilicate-functionalized polycaprolactone(PCL/LAP)was fabricated by 3D printing technology,and its bioactivities in bone regeneration were investigated in vitro and in vivo.In vitro experiments demonstrated that PCL/LAP exhibited good cytocompatibility and enhanced the viability of bone marrow mesenchymal stem cells(BMSCs).PCL/LAP functioned to stimulate osteogenic differentiation of BMSCs at the mRNA and protein levels and elevated angiogenic gene expression and cytokine secretion.Moreover,BMSCs cultured on PCL/LAP promoted the angiogenesis potential of endothelial cells by angiogenic cytokine secretion.Then,PCL/LAP scaffolds were implanted into the calvarial defect model.Toxicological safety of PCL/LAP was confirmed,and significant enhancement of vascularized bone formation was observed.Taken together,3D-printed PCL/LAP scaffolds with brilliant osteogenesis to enhance bone regeneration could be envisaged as an outstanding bone substitute for a promising change in oral-maxillofacial bone defect reconstruction.

In vitro insights into the role of copper ions released from selective laser melted CoCrW-xCu alloys in the potential attenuation of inflammation and osteoclastogenesis

In this study,the CoCrW-x Cu alloys(x=2,3 and 4 wt%)were fabricated using selective laser melting(abbreviated as Co-2 Cu,Co-3 Cu and Co-4Cu)with the purpose of reducing the inflammation responses and the activity of osteoclast.The metal ions releasing test showed that when the Cu content was less than 4 wt%,the releasing amount of Co and Cr ions was very small;however,when 4 wt%Cu was added in the CoCrW based alloy,the quantity of Co ions was significantly elevated with respect to the other groups due to the segregation of precipitates in the matrix;the Cu2+ion quantity of the Co-2Cu,Co-3Cu and Co-4Cu alloys were 0.05,0.09 and 0.27 g/(L cm2)after 7 d immersion,respectively;the RT-q PCR and ELISA data indicated that the expression levels of the pro-inflammatory cytokines(TNF-αand IL-6)were down-regulated in the Co-3Cu and Co-4Cu groups,whereas the expression level of the anti-inflammatory cytokine(IL-10)was up-regulated in all CoCrW-x Cu alloys;meanwhile,the Cu-containing CoCrW alloys significantly down-regulated the expression of the NF-B signal pathway in a Cu content-dependent manner,and the downstream transcription factors of NF-B signal pathway including NFATc1,TRAP and Cath-K were also down-regulated via potentially manipulating the NF-B signal pathway.After comprehensive consideration,it is considered that the Co-3Cu alloy is a potential material for self-alleviating inflammatory responses.

Doping Gd^(3+)Ion in PDA-PHBV Coating on Ti6Al4V Alloy for Enhancing Corrosion Resistance and Proliferation of Human Gingival Fibroblasts and Human Umbilical Vein Endothelial Cells

In this study,we fabricated poly(3-hydroxybutyrate-3-hydroxyvalerate)(PHBV)coatings doped with Gd^(3+)(1,5,and 10×10^(−4) mol/L)on Ti6Al4V alloy for the first time to promote soft tissue sealing around dental implants.The corrosion resistance of Gd^(3+)-modified PHBV-coated Ti6Al4V was studied by electrochemical and immersion tests,respectively,whereas CCK-8 and RT-PCR evaluated the biocompatibility to human gingival fibroblasts(HGFs)and human umbilical vein endothelial cells(HUVECs).It was found that the Gd^(3+)-modified PHBV coating could enhance the corrosion resistance of Ti6Al4V.In vitro cell tests showed that PHBV coatings with and without Gd^(3+) addition could promote adhesion and proliferation of HGFs and HUVECs,showing a Gd^(3+) content-dependent manner.Moreover,it was found that the PDA-PHBV@1Gd showed the best proliferation to HGFs by up-regulating gene expressions of VINCULIN,ITGB1,and ITGA3,whereas the best response to HUVECs with the highest gene expression of eNOS and HIF-1αgenes was found in the PDA-PHBV@5Gd-coated group.

Tuning osteoporotic macrophage responses to favour regeneration by Cu-bearing titanium alloy in Porphyromonas gingivalis lipopolysaccharide-induced microenvironments

Guided bone regeneration in inflammatory microenvironments of osteoporotic patients with large alve-olar bone defects remains a great challenge.Macrophages are necessary for alveolar bone regeneration via their polarization and paracrine actions.Our previous studies showed that Cu-bearing Ti6AI4V alloys are capable of regulating macrophage responses.When considering the complexity of oral microenvir-onments,the influences of Cu-bearing Ti6AI4V alloys on osteoporotic macrophages in infectious microenvironments are worthy of further investigations.In this study,we fabricated Ti6AI4V-Cu alloy by selective laser melting technology and used Porphyromonas gingivalis lipopolysaccharide(P.g-LPS)to imitate oral pathogenic bacterial infections.Then,we evaluated the impacts of T6AI4V-Cu on osteoporotic macrophages in infectious microenvironments.Our results indicated that Ti6AI4V-Cu not only inhibited the P.g-LPS-induced M1 polarization and pro-inflammatory cytokine production of osteoporotic macrophages but also shifted polarization towards the pro-regenerative M2 phenotype and remarkably promoted antinflammatory cytokine release.In addition,T6AI4V-Cu effectively promoted the actity of COMMD1 to potentially repress NF-κB-mediated transcription.It is concluded that the Cubearing Ti6AI4V alloy results in ameliorated osteoporotic macrophage responses to create a favourable microenvironment under infectious conditions,which holds promise to develop a GBR-barrier membrane for alveolar bone regeneration of osteoporosis patients.