3D Bio-Printed Bone Scaffolds Incorporated with Natural Antibacterial Compounds

3D Bioprinting plays an irreplaceable role in bone tissue engineering. Shellac and curcumin are two natural compounds that are widely used in the food and pharmaceutical sectors. In this study, a new composite scaffold with good biocompatibility and antibacterial ability was manufactured by adding shellac and curcumin into the traditional bone scaffold through low-temperature three-dimensional printing (LT-3DP), and its impact on the osteoimmune microenvironment was evaluated.

Targeting ferroptosis suppresses osteocyte glucolipotoxicity and alleviates diabetic osteoporosis

Diabetic osteoporosis(DOP) is the leading complication continuously threatening the bone health of patients with diabetes. A key pathogenic factor in DOP is loss of osteocyte viability. However, the mechanism of osteocyte death remains unclear. Here, we identified ferroptosis, which is iron-dependent programmed cell death, as a critical mechanism of osteocyte death in murine models of DOP. The diabetic microenvironment significantly enhanced osteocyte ferroptosis in vitro, as shown by the substantial lipid peroxidation, iron overload, and aberrant activation of the ferroptosis pathway. RNA sequencing showed that heme oxygenase-1(HO-1) expression was notably upregulated in ferroptotic osteocytes. Further findings revealed that HO-1 was essential for osteocyte ferroptosis in DOP and that its promoter activity was controlled by the interaction between the upstream NRF2 and c-JUN transcription factors. Targeting ferroptosis or HO-1 efficiently rescued osteocyte death in DOP by disrupting the vicious cycle between lipid peroxidation and HO-1 activation, eventually ameliorating trabecular deterioration. Our study provides insight into DOP pathogenesis, and our results provide a mechanism-based strategy for clinical DOP treatment.

A multifunctional optoelectronic device based on 2D material with wide bandgap

Low-dimensional materials exhibit unique quantum confinement effects and morphologies as a result of their nanoscale size in one or more dimensions,making them exhibit distinctive physical properties compared to bulk counterparts.Among all low-dimensional materials,due to their atomic level thickness,two-dimensional materials possess extremely large shape anisotropy and consequently are speculated to have large optically anisotropic absorption.In this work,we demonstrate an optoelectronic device based on the combination of two-dimensional material and carbon dot with wide bandgap.High-efficient luminescence of carbon dot and extremely large shape anisotropy(>1500)of two-dimensional material with the wide bandgap of>4 eV cooperatively endow the optoelectronic device with multi-functions of optically anisotropic blue-light emission,visible light modulation,wavelength-dependent ultraviolet-light detection as well as blue fluorescent film assemble.This research opens new avenues for constructing multi-function-integrated optoelectronic devices via the combination of nanomaterials with different dimensions.

A 3D-bioprinted scaffold with doxycycline-controlled BMP2-expressing cells for inducing bone regeneration and inhibiting bacterial infection

Large bone defects face a high risk of pathogen exposure due to open wounds,which leads to high infection rates and delayed bone union.To promote successful repair of infectious bone defects,fabrication of a scaffold with dual functions of osteo-induction and bacterial inhibition is required.This study describes creation of an engineered progenitor cell line(C3H10T1/2)capable of doxycycline(DOX)-mediated release of bone morphogenetic protein-2(BMP2).Three-dimensional bioprinting technology enabled creation of scaffolds,comprising polycaprolactone/mesoporous bioactive glass/DOX and bioink,containing these engineered cells.In vivo and in vitro experiments confirmed that the scaffold could actively secrete BMP2 to significantly promote osteoblast differentiation and induce ectopic bone formation.Additionally,the scaffold exhibited broad-spectrum antibacterial capacity,thereby ensuring the survival of embedded engineered cells when facing high risk of infection.These findings demonstrated the efficacy of this bioprinted scaffold to release BMP2 in a controlled manner and prevent the occurrence of infection;thus,showing its potential for repairing infectious bone defects.

Multi-omics analysis based on 3D-bioprinted models innovates therapeutic target discovery of osteosarcoma

Current in vitro models for osteosarcoma investigation and drug screening,including two-dimensional(2D)cell culture and tumour spheroids(i.e.cancer stem-like cells),lack extracellular matrix(ECM).Therefore,results from traditional models may not reflect real pathological processes in genuine osteosarcoma histological structures.Here,we report a three-dimensional(3D)bioprinted osteosarcoma model(3DBPO)that contains osteosarcoma cells and shrouding ECM analogue in a 3D frame.Photo-crosslinkable bioinks composed of gelatine methacrylamide and hyaluronic acid methacrylate mimicked tumour ECM.We performed multi-omics analysis,including transcriptomics and DNA methylomics,to determine differences between the 3DBPO model and traditional models.Compared with 2D models and tumour spheroids,our 3DBPO model showed significant changes in cell cycle,metabolism,adherens junctions,and other pathways associated with epigenetic regulation.The 3DBPO model was more sensitive to therapies targeted to the autophagy pathway.We showed that simulating ECM yielded different osteosarcoma cell metabolic characteristics and drug sensitivity in the 3DBPO model compared with classical models.We suggest 3D printed osteosarcoma models can be used in osteosarcoma fundamental and translational research,which may contribute to novel therapeutic strategy discovery.

CTCF acetylation at lysine 20 is required for the early cardiac mesoderm differentiation of embryonic stem cells

The CCCTC-binding factor(CTCF)protein and its modified forms regulate gene expression and genome organization.However,information on CTCF acetylation and its biological function is still lacking.Here,we show that CTCF can be acetylated at lysine 20(CTCF-K20)by CREB-binding protein(CBP)and deacetylated by histone deacetylase 6(HDAC6).CTCF-K20 is required for the CTCF interaction with CBP.A CTCF point mutation at lysine 20 had no effect on self-renewal but blocked the mesoderm differentiation of mouse embryonic stem cells(mESCs).The CTCF-K20 mutation reduced CTCF binding to the promoters and enhancers of genes associated with early cardiac mesoderm differentia-tion,resulting in diminished chromatin accessibility and decreased enhancer-promoter interactions,impairing gene expression.In summary,this study reveals the important roles of CTCF-K20 in regulating CTCF genomic functions and mESC differentiation into mesoderm.

Turning gray selenium into a nanoaccelerator of tissue regeneration by PEG modification

Selenium(Se)is an essential trace element involved in nearly all human physiological processes but suffers from a narrow margin between benefit and toxicity.The nanoform of selenium has been proven shown to be more bioavailable and less toxic,yet significant challenges remain regarding the efficient and feasible synthesis of biologically active nanoselenium.In addition,although nanoselenium has shown a variety of biological activities,more interesting nanoselenium features are expected.In this work,hydrosoluble nanoselenium termed Nano-Se in the zero oxidation state was synthesized between gray Se and PEG.A zebrafish screen was carried out in zebrafish larvae cocultured with Nano-Se.Excitingly,Nano-Se promoted the action of the FGFR,Wnt,and VEGF signaling pathways,which play crucial roles in tissue regeneration.As expected,Nano-Se not only achieved the regeneration of zebrafish tail fins and mouse skin but also promoted the repair of skin in diabetic mice while maintaining a profitable safe profile.In brief,the Nano-Se reported here provided an efficient and feasible method for bioactive nanoselenium synthesis and not only expanded the application of nanoselenium to regenerative medicine but also likely reinvigorated efforts for discovering more peculiarunique biofunctions of nanoselenium in a great variety of human diseases.