Constructing a biofunctionalized 3D-printed gelatin/sodium alginate/chitosan tri-polymer complex scaffold with improvised biological andmechanical properties for bone-tissue engineering

Sodium alginate(SA)/chitosan(CH)polyelectrolyte scaffold is a suitable substrate for tissue-engineering application.The present study deals with further improvement in the tensile strength and biological properties of this type of scaffold to make it a potential template for bone-tissue regeneration.We experimented with adding 0%–15%(volume fraction)gelatin(GE),a protein-based biopolymer known to promote cell adhesion,proliferation,and differentiation.The resulting tri-polymer complex was used as bioink to fabricate SA/CH/GEmatrices by three-dimensional(3D)printing.Morphological studies using scanning electron microscopy revealed the microfibrous porous architecture of all the structures,which had a pore size range of 383–419μm.X-ray diffraction and Fourier-transform infrared spectroscopy analyses revealed the amorphous nature of the scaffold and the strong electrostatic interactions among the functional groups of the polymers,thereby forming polyelectrolyte complexes which were found to improve mechanical properties and structural stability.The scaffolds exhibited a desirable degradation rate,controlled swelling,and hydrophilic characteristics which are favorable for bone-tissue engineering.The tensile strength improved from(386±15)to(693±15)kPa due to the increased stiffness of SA/CH scaffolds upon addition of gelatin.The enhanced protein adsorption and in vitro bioactivity(forming an apatite layer)confirmed the ability of the SA/CH/GE scaffold to offer higher cellular adhesion and a bone-like environment to cells during the process of tissue regeneration.In vitro biological evaluation including the MTT assay,confocal microscopy analysis,and alizarin red S assay showed a significant increase in cell attachment,cell viability,and cell proliferation,which further improved biomineralization over the scaffold surface.In addition,SA/CH containing 15%gelatin designated as SA/CH/GE15 showed superior performance to the other fabricated 3D structures,demonstrating its potential for use in bone-tissue engineering.

Exosomes in viral infection:Effects for pathogenesis and treatment strategies

Exosomes are small vesicles that carry molecules from one cell to another.They have many features that make them interesting for research,such as their stability,low immunogenicity,size of the nanoscale,toxicity,and selective delivery.Exosomes can also interact with viruses in diverse ways.Emerging research highlights the significant role of exosomes in viral infections,particularly in the context of diseases like COVID-19,HIV,HBV and HCV.Understanding the intricate interplay between exosomes and the human immune system holds great promise for the development of effective antiviral therapies.An important aspect is gaining clarity on how exosomes influence the immune system and enhance viral infectivity through their inherent characteristics.By leveraging the innate properties of exosomes,viruses exploit the machinery involved in exosome biogenesis to set replication,facilitate the spread of infection,and eliminate immune responses.They can either help or hinder viral infection by modulating the immune system.This review summarizes the recent findings on how exosomes mediate viral infection and how they can be used for diagnosis or therapy.This could lead to new clinical applications of exosomes in disease management.

From waste of marine culture to natural patch in cardiac tissue engineering

Sea squirt,as a highly invasive species and main biofouling source in marine aquaculture,has seriously threatened the biodiversity and aquaculture economy.On the other hand,a conductive biomaterial with excellent biocompatibility,and appropriate mechanical property from renewable resources is urgently required for tissue engineering patches.To meet these targets,we presented a novel and robust strategy for sustainable development aiming at the marine pollution via recycling and upgrading the waste biomass-sea squirts and serving as a renewable resource for functional bio-scaffold patch in tissue engineering.We firstly demonstrated that the tunic cellulose derived natural self-conductive scaffolds successfully served as functional cardiac patches,which significantly promote the maturation and spontaneous contraction of cardiomyocytes both in vitro and enhance cardiac function of MI rats in vivo.We believe this novel,feasible and“Trash to Treasure”strategy to gain cardiac patches via recycling the waste biomass must be promising and beneficial for marine environmental bio-pollution issue and sustainable development considering the large-scale consumption potential for tissue engineering and other applications.

Phosphorylation inhibition of protein-tyrosine phosphatase 1B tyrosine-152 induces bone regeneration coupled with angiogenesis for bone tissue engineering

A close relationship has been reported to exist between cadherin-mediated cell-cell adhesion and integrin-mediated cell mobility,and protein tyrosine phosphatase 1B(PTP1B)may be involved in maintaining this homeostasis.The stable residence of mesenchymal stem cells(MSCs)and endothelial cells(ECs)in their niches is closely related to the regulation of PTP1B.However,the exact role of the departure of MSCs and ECs from their niches during bone regeneration is largely unknown.Here,we show that the phosphorylation state of PTP1B tyrosine-152(Y152)plays a central role in initiating the departure of these cells from their niches and their subsequent recruitment to bone defects.Based on our previous design of a PTP1B Y152 region-mimicking peptide(152RM)that significantly inhibits the phosphorylation of PTP1B Y152,further investigations revealed that 152RM enhanced cell migration partly via integrinαvβ3 and promoted MSCs osteogenic differentiation partly by inhibiting ATF3.Moreover,152RM induced type H vessels formation by activating Notch signaling.Demineralized bone matrix(DBM)scaffolds were fabricated with mesoporous silica nanoparticles(MSNs),and 152RM was then loaded onto them by electrostatic adsorption.The DBM-MSN/152RM scaffolds were demonstrated to induce bone formation and type H vessels expansion in vivo.In conclusion,our data reveal that 152RM contributes to bone formation by coupling osteogenesis with angiogenesis,which may offer a potential therapeutic strategy for bone defects.

Angelica sinensis polysaccharides ameliorate 5-flourouracil-induced bone marrow stromal cell proliferation inhibition via regulating Wnt/β-catenin signaling

Chemotherapy may cause cellular oxidative stress to bone marrow.Oxidative damage of bone marrow hematopoietic microenvironment is closely related to chronic myelosuppression after chemotherapeutic treatment.Angelica sinensis polysaccharides(ASP)are major effective ingredients of traditional Chinese medicine Angelica with multi-target anti-oxidative stress features.In the current study,we investigated the protective roles and mechanisms of ASP on chemotherapy-induced bone marrow stromal cell(BMSC)damage.The human bone marrow stromal cell line HS-5 cells were divided into control group,5-FU group,5-FU+ASP group,and 5-FU+LiCl group to investigate the mechanism of ASP to alleviate 5-FU-induced BMSC proliferation inhibition.The results showed that 5-FU inhibits the growth of HS-5 cells in a time and dose-dependent manner;however,ASP partially counteracted the 5-FU-induced decrease in cell viability,whereas Wnt signaling inhibitor Dkk1 antagonized the effect of ASP on HS-5 cells.ASP reversed the decrease in total cytoplasmicβ-catenin,p-GSK-3β,and CyclinD1 following 5-FU treatment and modulated nuclear expression ofβ-catenin,Lef-1,and C-myc proteins.Furthermore,ASP also enhanced the antioxidant capacity of cells and reduced 5-FU-induced oxidative stress,attenuated FoxO1 expression,thus weakened its downstream apoptosis-related proteins and G0/G1 checkpoint-associated p27^(Kip1) expression to alleviate 5-FU-induced apoptosis and to promote cell cycle progression.All the results above suggest that the protective role of ASP in 5-FU-treated BMSCs proliferation for the chemotherapy may be related to its activating Wnt/β-catenin signaling and keeping homeostasis betweenβ-catenin and FoxO1 under oxidative stress.The study provides a potential therapeutic strategy for alleviating chemotherapeutic damage on BMSCs.

RNA-binding protein LIN28B inhibits apoptosis through regulation of the AKT2/FOXO3A/BIM axis in ovarian cancer cells

LIN28B is an evolutionarily conserved RNA-binding protein that regulates mRNA translation and miRNA let-7 maturation in embryonic stem cells and developing tissues.Increasing evidence demonstrates that LIN28B is activated in cancer and serves as a critical oncogene.However,the underlying molecular mechanisms of LIN28B function in tumorigenesis are still largely unknown.Here we report that LIN28B was expressed in over half of the patients with epithelial ovarian cancer who were examined(n=584).Functional experiments demonstrated that LIN28B inhibited ovarian cancer cell apoptosis.Furthermore,we showed that the proapoptotic factor BIM played an essential role in the antiapoptotic function of LIN28B.RNA-IP microarray analysis suggested that LIN28B binds to mRNAs that are associated with the DNA damage pathway,such as AKT2,in ovarian cancer cells.By binding to AKT2 mRNA and enhancing its protein expression,LIN28B regulated FOXO3A protein phosphorylation and decreased the transcriptional level of BIM,which antagonized the antiapoptosis activity of LIN28B.Taken together,these results mechanistically linked LIN28B and the AKT2/FOXO3A/BIM axis to the apoptosis pathway.The findings may have important implications in the diagnosis and therapeutics of ovarian cancer.