Continuously released Zn^(2+)in 3D-printed PLGA/β-TCP/Zn scaffolds for bone defect repair by improving osteoinductive and anti-inflammatory properties

Long-term nonunion of bone defects has always been a major problem in orthopedic treatment.Artificial bone graft materials such as Poly(lactic-co-glycolic acid)/β-tricalcium phosphate(PLGA/β-TCP)scaffolds are expected to solve this problem due to their suitable degradation rate and good osteoconductivity.However,insufficient mechanical properties,lack of osteoinductivity and infections after implanted limit its large-scale clinical application.Hence,we proposed a novel bone repair bioscaffold by adding zinc submicron particles to PLGA/β-TCP using low temperature rapid prototyping 3D printing technology.We first screened the scaffolds with 1 wt%Zn that had good biocompatibility and could stably release a safe dose of zinc ions within 16 weeks to ensure long-term non-toxicity.As designed,the scaffold had a multi-level porous structure of biomimetic cancellous bone,and the Young’s modulus(63.41±1.89 MPa)and compressive strength(2.887±0.025 MPa)of the scaffold were close to those of cancellous bone.In addition,after a series of in vitro and in vivo experiments,the scaffolds proved to have no adverse effects on the viability of BMSCs and promoted their adhesion and osteogenic differentiation,as well as exhibiting higher osteogenic and anti-inflammatory properties than PLGA/β-TCP scaffold without zinc particles.We also found that this osteogenic and anti-inflammatory effect might be related to Wnt/β-catenin,P38 MAPK and NFkB pathways.This study lay a foundation for the follow-up study of bone regeneration mechanism of Zn-containing biomaterials.We envision that this scaffold may become a new strategy for clinical treatment of bone defects.

A Global Multiregional Proteomic Map of the Human Cerebral Cortex

The Brodmann area(BA)-based map is one of the most widely used cortical maps for studies of human brain functions and in clinical practice;however,the molecular architecture of BAs remains unknown.The present study provided a global multiregional proteomic map of the human cerebral cortex by analyzing 29 BAs.These 29 BAs were grouped into 6 clusters based on similarities in proteomic patterns:the motor and sensory cluster,vision cluster,auditory and Broca’s area cluster,Wernicke’s area cluster,cingulate cortex cluster,and heterogeneous function cluster.We identified 474 cluster-specific and 134 BA-specific signature proteins whose functions are closely associated with specialized functions and disease vulnerability of the corresponding cluster or BA.The findings of the present study could provide explanations for the functional connections between the anterior cingulate cortex and sensorimotor cortex and for anxiety-related function in the sensorimotor cortex.The brain transcriptome and proteome comparison indicates that they both could reflect the function of cerebral cortex,but show different characteristics.These proteomic data are publicly available at the Human Brain Proteome Atlas(www.brain-omics.com).Our results may enhance our understanding of the molecular basis of brain functions and provide an important resource to support human brain research.

Proteomic analysis of human frontal and temporal cortex using iTRAQ-based 2D LCMS/MS

Background:The human brain is the most complex organ in the body,and it is important to have a better understanding of how the protein composition in the brain regions contributes to the pathogenesis of associated neurological disorders.Methods:In this study,a comparative analysis of the frontal and temporal cortex proteomes was conducted by isobaric tags of relative and absolute quantification(iTRAQ)labeling and two-dimensional liquid chromatographytandem mass spectrometry(2D LC-MS/MS).Brain protein was taken from relatively normal tissue that could not be avoided of damage during emergent surgery of the TBI(traumatic brain injury)patients admitted in Beijing Tiantan Hospital from 2014 to 2017.Eight cases were included.Four frontal lobes and 4 temporal lobes proteome were analyzed and the proteins were quantitated.Gene Ontology(GO),Ingenuity Pathway Analysis(IPA),and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were used to analyze the biological function of identified proteins,unchanged proteins,and differentially expressed proteins(DEPs).Results:A total number of 2127 protein groups were identified in the frontal and temporal lobe proteomes.A total of 1709 proteins could be quantitated in both the frontal and temporal cortex.Among 90 DEPs,14 proteins were screened highly expressed in the temporal cortex,including MAPT,SNCG,ATP5IF1,GAP43,HSPE1,STMN1,NDUFS6,LDHB,SNCB,NDUFA7,MRPS36,EPDR1,CISD1,and RALA.In addition,compared to proteins expressed in the frontal cortex,14 proteins including EDC4,NIT2,VWF,ASTN1,TGM2,SSB,CLU,HBA1,STOM,CRP,LRG1,SAA2,S100A4,and VTN were a low expression in the temporal cortex.The biological process enrichment showed that unchanged proteins between the frontal and temporal cortex mainly take part in regulated exocytosis,axon guidance,and vesicle-mediated transport.The KEGG pathway analysis showed that unchanged proteins between the frontal and temporal cortex mainly take part in oxidative phosphorylation,carbon metabolism,Huntington’s disease,and Parkinson’s disease.Conclusions:The majority of proteins are unchanged between the frontal and temporal cortex,and unchanged proteins are closely related to its function.Among DEPs,MATP(tau)is upregulated in the temporal cortex,closely related to Alzheimer’s disease(AD),and is one of the targets for the treatment of AD.CLU is downregulated in the temporal cortex which functions as an extracellular chaperone that prevents aggregation of non-native proteins.It was suggested that the temporal lobe may not be the“functional dumb area”of the traditional view,but could be involved in important neural metabolic circuits.