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.

Magnesium alloys in tumor treatment:Current research status, challenges and future prospects

Cancer is a major threat to human life worldwide. Traditional cancer treatments, such as chemotherapy and surgery, have major limitations and can cause irreversible damage to normal tissues while killing the cancer cells. Magnesium(Mg) alloys are widely reported novel potential biomedical materials with acceptable mechanical properties and good osteogenic and angiogenic properties. In this review, we summarize the Mg alloys for antitumor applications, including pure Mg and Mg alloys(Mg-Ag, Mg-Gd, Mg-Li-Zn, Mg-Ca-Sr-Zn, et al.) fabricated by casting and extruding, selective laser melting methods. Mg alloys can exhibit antitumor effect on bone tumor, breast cancer, and liver tumor,etal. What's more, after tumor tissue is eliminated, Mg alloys prevent tumor recurrence, fill tissue defects and promote tissue regeneration.The antitumor effects of Mg alloys are mainly due to their degradation products. Overall, Mg alloys show great potential in tumor treatments due to the dual function of antitumor and tissue regeneration.

Drug target discovery by magnetic nanoparticles coupled mass spectrometry

Drug target discovery is the basis of drug screening.It elucidates the cause of disease and the mechanism of drug action,which is the essential of drug innovation.Target discovery performed in biological systems is complicated as proteins are in low abundance and endogenous compounds may interfere with drug binding.Therefore,methods to track drug-target interactions in biological matrices are urgently required.In this work,a Fe_(3)O_(4) nanoparticle-based approach was developed for drug-target screening in biofluids.A known ligand-protein complex was selected as a principle-to-proof example to validate the feasibility.After incubation in cell lysates,ligand-modified Fe_(3)O_(4) nanoparticles bound to the target protein and formed complexes that were separated from the lysates by a magnet for further analysis.The large surface-to-volume ratio of the nanoparticles provides more active sites for the modification of chemical drugs.It enhances the opportunity for ligand-protein interactions,which is beneficial for capturing target proteins,especially for those with low abundance.Additionally,a one-step magnetic separation simplifies the pre-processing of ligand-protein complexes,so it effectively reduces the endogenous interference.Therefore,the present nanoparticle-based approach has the potential to be used for drug target screening in biological systems.

Advances in the detec

Human health is threatened by foodborne illness and Staphylococcus aureus is a common foodborne pathogenic bacteria.It can cause food poisoning when we are infected,therefore,it is necessary to detect pathogenic bacteria.The virulence genes and detection methods of S.aureus are summarized from literatures.Traditional detection methods are simple but need bacteria enrichment and to prolong detection time.Immunological technology has high specificity,but false positive results are easy to occur in its detection.In recent years,molecular biology methods have developed rapidly,and various PCR techniques have been applied to detect foodborne pathogens.Real-time fluorescent quantitative PCR is more effective than ordinary PCR,while price is expensive when use it,the scope of use is limited.LAMP is a flexible detection method,biosensor and flow cytometry are fast but the cost of detection is high and the price is relatively expensive.

Surface modification strategies to reinforce the soft tissue seal at transmucosal region of dental implants

Soft tissue seal around the transmucosal region of dental implants is crucial for shielding oral bacterial invasion and guaranteeing the long-term functioning of implants.Compared with the robust periodontal tissue barrier around a natural tooth,the peri-implant mucosa presents a lower bonding efficiency to the transmucosal region of dental implants,due to physiological structural differences.As such,the weaker soft tissue seal around the transmucosal region can be easily broken by oral pathogens,which may stimulate serious inflammatory responses and lead to the development of peri-implant mucositis.Without timely treatment,the curable peri-implant mucositis would evolve into irreversible peri-implantitis,finally causing the failure of implantation.Herein,this review has summarized current surface modification strategies for the transmucosal region of dental implants with improved soft tissue bonding capacities(e.g.,improving surface wettability,fabricating micro/nano topographies,altering the surface chemical composition and constructing bioactive coatings).Furthermore,the surfaces with advanced soft tissue bonding abilities can be incorporated with antibacterial properties to prevent infections,and/or with immunomodulatory designs to facilitate the establishment of soft tissue seal.Finally,we proposed future research orientations for developing multifunctional surfaces,thus establishing a firm soft tissue seal at the transmucosal region and achieving the long-term predictability of dental implants.

Plasma spray of biofunctional(Mg, Sr)-substituted hydroxyapatite coatings for titanium alloy implants

Plasma-sprayed hydroxyapatite (HA) coatings have been widely utilized in load-bearing titanium alloy implants. In this study, Mg, Sr co-substituted HA ((Mg,Sr)-HA) nano-scale powders have been synthesized, which are further used to prepare (Mg,Sr)-HA coatings on Ti-6A1-4V alloys in order to improve the biological functions. The average size of (Mg,Sr)-HA nano particles is ~75nm. The average bonding strength for (Mg,Sr)-HA coating and samples after heat treatment at 500℃ or 600℃ for 3h are 26.17±2.11 MPa, 36.07±4.48 MPa and 37.07 ±2.95 MPa, respectively. There is a significantly increase of bonding strength likely due to low residual stress after heated treatment.MC3T3-E1 cells show a high proliferation rate when cultured with (Mg,Sr)-HA coating extract compared to the normal culture medium, which also exhibit large extension and depositi on of extracellular matrices when adhered on the coating surfaces. Thus, these (Mg,Sr)-HA coatings show high bonding strength and improved biological functions, which offer promising future applications in the fields of orthopedics and dentistry.

Research status of biodegradable metals designed for oral and maxillofacial applications:A review

The oral and maxillofacial regions have complex anatomical structures and different tissue types,which have vital health and aesthetic functions.Biodegradable metals(BMs)is a promising bioactive materials to treat oral and maxillofacial diseases.This review summarizes the research status and future research directions of BMs for oral and maxillofacial applications.Mg-based BMs and Zn-based BMs for bone fracture fixation systems,and guided bone regeneration(GBR)membranes,are discussed in detail.Zn-based BMs with a moderate degradation rate and superior mechanical properties for GBR membranes show great potential for clinical translation.Fe-based BMs have a relatively low degradation rate and insoluble degradation products,which greatly limit their application and clinical translation.Furthermore,we proposed potential future research directions for BMs in the oral and maxillofacial regions,including 3D printed BM bone scaffolds,surface modification for BMs GBR membranes,and BMs containing hydrogels for cartilage regeneration,soft tissue regeneration,and nerve regeneration.Taken together,the progress made in the development of BMs in oral and maxillofacial regions has laid a foundation for further clinical translation.

Biomimetic AgNPs@antimicrobial peptide/silk fibroin coating for infection-trigger antibacterial capability and enhanced osseointegration

Endowing implant surfaces with combined antibacterial and osteogenic properties by drug-loaded coatings has made great strides,but how to achieve the combined excellence of infection-triggered bactericidal and in vivo-proven osteogenic activities without causing bacterial resistance still remains a formidable challenge.Herein,antimicrobial peptides(AMPs)with osteogenic fragments were designed and complexed on the surface of silver nanoparticle(AgNP)through hydrogen bonding,and the collagen structure-bionic silk fibroin(SF)was applied to carry AgNPs@AMPs to achieve infection-triggered antibacterial and osteointegration.As verified by TEM,AMPs contributed to the dispersion and size-regulation of AgNPs,with a particle size of about 20 nm,and a clear protein corona structure was observed on the particle surface.The release curve of silver ion displayed that the SF-based coating owned sensitive pH-responsive properties.In the antibacterial test against S.aureus for up to 21 days,the antibacterial rate had always remained above 99%.Meanwhile,the underlying mechanism was revealed,originating from the destruction of the bacterial cell membranes and ROS generation.The SF-based coating was conducive to the adhesion,diffusion,and proliferation of bone marrow stem cells(BMSCs)on the surface,and promoted the expression of osteogenic genes and collagen secretion.The in vivo implantation results showed that compared with the untreated Ti implants,SF-based coating enhanced osseointegration at week 4 and 8.Overall,the AgNPs@AMPs-loaded SF-based coating presented the ability to synergistically inhibit bacteria and promote osseointegration,possessing tremendous potential application prospects in bone defects and related-infection treatments.

A review on current research status of the surface modification of Zn-based biodegradable metals

Recently,zinc and its alloys have been proposed as promising candidates for biodegradable metals(BMs),owning to their preferable corrosion behavior and acceptable biocompatibility in cardiovascular,bone and gastrointestinal environments,together with Mg-based and Fe-based BMs.However,there is the desire for surface treatment for Zn-based BMs to better control their biodegradation behavior.Firstly,the implantation of some Zn-based BMs in cardiovascular environment exhibited intimal activation with mild inflammation.Secondly,for orthopedic applications,the biodegradation rates of Zn-based BMs are relatively slow,resulting in a long-term retention after fulfilling their mission.Meanwhile,excessive Zn2+release during degradation will cause in vitro cytotoxicity and in vivo delayed osseointegration.In this review,we firstly summarized the current surface modification methods of Zn-based alloys for the industrial applications.Then we comprehensively summarized the recent progress of biomedical bulk Zn-based BMs as well as the corresponding surface modification strategies.Last but not least,the future perspectives towards the design of surface bio-functionalized coatings on Zn-based BMs for orthopedic and cardiovascular applications were also briefly proposed.

In vitro and in vivo investigation on biodegradable Mg-Li-Ca alloys for bone implant application

Magnesium alloys show promise for application in orthopedic implants, owing to their biodegradability and biocompatibility. In the present study, ternary Mg-(3.5,6.5 wt%) Li-(0.2, 0.5, 1.0 wt%) Ca alloys were developed. Their mechanical strength, corrosion behavior and cytocompatibility were studied. These alloys showed improved mechanical strength than pure Mg and exhibited suitable corrosion resistance. Furthermore, Mg-3.5Li-0.5Ca alloys with the best in vitro performance were implanted intramedullary into the femurs of mice for 2 and 8 weeks. In vivo results revealed a significant increase in cortical bone thickness around the Mg-3.5Li-0.5Ca alloy rods, without causing any adverse effects.Western blotting and immunofluorescence staining of β-catenin illustrated that Mg-3.5Li-0.5Ca alloy extracts induced osteogenic differentiation of human bone marrow-derived mesenchymal stem cells(hBMMSCs) through the canonical Wnt/β-catenin pathway. Our studies demonstrate that Mg-3.5Li-0.5Ca alloys hold much promise as candidates for the facilitation of bone implant application.

Additively manufactured pure zinc porous scaffolds for critical-sized bone defects of rabbit femur

Additive manufacturing has received attention for the fabrication of medical implants that have customized and complicated structures.Biodegradable Zn metals are revolutionary materials for orthopedic implants.In this study,pure Zn porous scaffolds with diamond structures were fabricated using customized laser powder bed fusion(L-PBF)technology.First,the mechanical properties,corrosion behavior,and biocompatibility of the pure Zn porous scaffolds were characterized in vitro.The scaffolds were then implanted into the rabbit femur critical-size bone defect model for 24 weeks.The results showed that the pure Zn porous scaffolds had compressive strength and rigidity comparable to those of cancellous bone,as well as relatively suitable degradation rates for bone regeneration.A benign host response was observed using hematoxylin and eosin(HE)staining of the heart,liver,spleen,lungs,and kidneys.Moreover,the pure Zn porous scaffold showed good biocompatibility and osteogenic promotion ability in vivo.This study showed that pure Zn porous scaffolds with customized structures fabricated using L-PBF represent a promising biodegradable solution for treating large bone defects.

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.

Hydrogen selenide,a vital metabolite of sodium selenite,uncouples the sulfilimine bond and promotes the reversal of liver fibrosis

Sodium selenite has alleviating effects on liver fibrosis;however,its therapeutic molecular mechanism remains unclear.Herein,hydrogen selenide,a major metabolite of Na_(2)SeO_(3),was tested to uncouple the sulfilimine bond in collagen IV,the biomarker of liver fibrosis.A mouse model of liver fibrosis was constructed via a CCl_(4)-induced method,followed by the administration of 0.2 mg kg−1 Na_(2)SeO_(3)via gavage three times per week for 4 weeks.Changes in H2Se,NADPH,and H_(2)O_(2)levels were monitored in real time by using NIR-H2Se,DCI-MQ-NADPH,and H_(2)O_(2)probes in vivo,respectively.H_(2)Se continuously accumulated in the liver throughout the Na_(2)SeO_(3)treatment period,but the levels of NADPH and H_(2)O_(2)decreased.The expression of collagen IV was analyzed through Western blot and liquid chromatography-mass spectrometry.Results confirmed that the sulfilimine bond of collagen IV in the fibrotic mouse livers could be broken by H2Se with the Na_(2)SeO_(3)treatment.Therefore,the therapeutic effect of Na_(2)SeO_(3)on liver fibrosis could be mainly attributed to H_(2)Se that uncoupled the sulfilimine bond to induce collagen IV degradation.This study provided a reasonable explanation for the molecular mechanism of the in vivo function of Na_(2)SeO_(3)and the prevention of liver fibrosis by administering inorganic selenium.

Synthesis of few-layer N-doped graphene from expandable graphite with melamine and its application in supercapacitors

In this paper,we introduced a novel method to prepare the few-layer nitrogen-doped graphene(FNG)from expandable graphite with melamine.The super-capacitive properties of FNG were thoroughly characterized by a three-electrode system,and the results showed the FNG electrode achieved a specific capacitance as high as 83.8 mF/cm2 together with excellent cycling stability.This method could be a novel approach to combine the pseudo-capacitors and electric double layer capacitors.

Systematic in vitro and in vivo study on biodegradable binary Zn-0.2 at%Rare Earth alloys(Zn-RE:Sc,Y,La-Nd,Sm-Lu)

Biomedical implants and devices for tissue engineering in clinics,mainly made of polymers and stiff metallic materials,require possibly secondary surgery or life-long medicine.Biodegradable metals for biomedical implants and devices exhibit huge potential to improve the prognosis of patients.In this work,we developed a new type of biodegradable binary zinc(Zn)alloys with 16 rare earth elements(REEs)including Sc,Y,La to Nd,and Sm to Lu,respectively.The effects of REEs on the alloy microstructure,mechanical properties,corrosion behavior and in vitro and in vivo biocompatibility of Zn were systematically investigated using pure Zn as control.All Zn-RE alloys generally exhibited improved mechanical properties,and biocompatibilities compared to pure Zn,especially the tensile strength and ductility of Zn-RE alloys were dramatically enhanced.Among the Zn-RE alloys,different REEs presented enhancement effects at varied extent.Y,Ho and Lu were the three elements displaying greatest improvements in majority of alloys properties,while Eu,Gd and Dy exhibited least improvement.Furthermore,the Zn-RE alloys were comparable with other Zn alloys and also exhibited superior properties to Mg-RE alloys.The in vivo experiment using Zn-La,Zn-Ce,and Zn-Nd alloys as tibia bone implants in rabbit demonstrated the excellent tissue biocompatibility and much more obvious osseointegration than the pure Zn control group.This work presented the significant potential of the developed Zn-RE binary alloys as novel degradable metal for biomedical implants and devices.

Sustained release of magnesium and zinc ions synergistically accelerates wound healing

Skin wounds are a major medical challenge that threaten human health.Functional hydrogel dressings demonstrate great potential to promote wound healing.In this study,magnesium(Mg)and zinc(Zn)are introduced into methacrylate gelatin(GelMA)hydrogel via low-temperature magnetic stirring and photocuring,and their effects on skin wounds and the underlying mechanisms are investigated.Degradation testing confirmed that the GelMA/Mg/Zn hydrogel released magnesium ions(Mg^(2+))and zinc ions(Zn^(2+))in a sustained manner.The Mg^(2+) and Zn^(2+)not only enhanced the migration of human skin fibroblasts(HSFs)and human immortalized keratinocytes(HaCats),but also promoted the transformation of HSFs into myofibroblasts and accelerated the production and remodeling of extracellular matrix.Moreover,the GelMA/Mg/Zn hydrogel enhanced the healing of full-thickness skin defects in rats via accelerated collagen deposition,angiogenesis and skin wound re-epithelialization.We also identified the mechanisms through which GelMA/Mg/Zn hydrogel promoted wound healing:the Mg^(2+) promoted Zn^(2+)entry into HSFs and increased the concentration of Zn^(2+)in HSFs,which effectively induced HSFs to differentiate into myofibroblasts by activating the STAT3 signaling pathway.The synergistic effect of Mg^(2+) and Zn^(2+)promoted wound healing.In conclusion,our study provides a promising strategy for skin wounds regeneration.