May-Thurner syndrome(MTS) is the pathologic compression of the left common iliac vein by the right common iliac artery, resulting in left lower extremity pain, swelling, and deep venous thrombosis. Though this syndrom...May-Thurner syndrome(MTS) is the pathologic compression of the left common iliac vein by the right common iliac artery, resulting in left lower extremity pain, swelling, and deep venous thrombosis. Though this syndrome was first described in 1851, there are currently no standardized criteria to establish the diagnosis of MTS. Since MTS is treated by a wide array of specialties, including interventional radiology, vascular surgery, cardiology, and vascular medicine, the need for an established diagnostic criterion is imperative in order to reduce misdiagnosis and inappropriate treatment. Although MTS has historically been diagnosed by the presence of pathologic features, the use of dynamic imaging techniques has led to a more radiologic based diagnosis. Thus, imaging plays an integral part in screening patients for MTS, and the utility of a wide array of imaging modalities has been evaluated. Here, we summarize the historical aspects of the clinical features of this syndrome. We then provide a comprehensive assessment of the literature on the efficacy of imaging tools available to diagnose MTS. Lastly, we provide clinical pearls and recommendations to aid physicians in diagnosing the syndrome through the use of provocative measures.展开更多
Protein exerts a critical influence on the degradation behavior of absorbable magnesium(Mg)-based implants.However,the interaction mechanism between protein and a micro-arc oxidation(MAO)coating on Mg alloys remains u...Protein exerts a critical influence on the degradation behavior of absorbable magnesium(Mg)-based implants.However,the interaction mechanism between protein and a micro-arc oxidation(MAO)coating on Mg alloys remains unclear.Hereby,a MAO coating was fabricated on AZ31 Mg alloy.And its degradation behavior in phosphate buffer saline(PBS)containing bovine serum albumin(BSA)was investigated and compared with that of the uncoated alloy.Surface morphologies and chemical compositions were studied using Field-emission scanning electron microscope(FE-SEM),Fourier transform infrared spectrophotometer(FT-IR)and X-ray diffraction(XRD).The degradation behavior of the bare Mg alloy and its MAO coating was studied through electrochemical and hydrogen evolution tests.Cytotoxicity assay was applied to evaluate the biocompatibility of Mg alloy substrate and MAO coating.Results indicated that the presence of BSA decreased the degradation rate of Mg alloy substrate because BSA(RCH(NH2)COO‾)molecules combined with Mg2+ions to form(RCH(NH2)COO)2Mg and thus inhibited the dissolution of Mg(OH)2 by impeding the attack of Cl‾ions.In the case of MAO coated Mg alloy,the adsorption of BSA on MAO coating and the formation of(RCH(NH2)COO)2Mg exhibited a synergistic effect and enhanced the corrosion resistance of the coated alloy significantly.Furthermore,cell bioactive assay suggested that the MAO coating had good viability for MG63 cells due to its high surface area.展开更多
In recent years,bone tissue engineering has emerged as a promising solution to the limitations of current gold standard treatment options for bone related-disorders such as bone grafts.Bone tissue engineering provides...In recent years,bone tissue engineering has emerged as a promising solution to the limitations of current gold standard treatment options for bone related-disorders such as bone grafts.Bone tissue engineering provides a scaffold design that mimics the extracellular matrix,providing an architecture that guides the natural bone regeneration process.During this period,a new generation of bone tissue engineering scaffolds has been designed and characterized that explores the incorporation of signaling molecules in order to enhance cell recruitment and ingress into the scaffold,as well as osteogenic differentiation and angiogenesis,each of which is crucial to successful bone regeneration.Here,we outline and critically analyze key characteristics of successful bone tissue engineering scaffolds.We also explore candidate materials used to fabricate these scaffolds.Different growth factors involved in the highly coordinated process of bone repair are discussed,and the key requirements of a growth factor delivery system are described.Finally,we concentrate on an analysis of scaffold-based growth factor delivery strategies found in the recent literature.In particular,the incorporation of two-phase systems consisting of growth factor-loaded nanoparticles embedded into scaffolds shows great promise,both by providing sustained release over a therapeutically relevant timeframe and the potential to sequentially deliver multiple growth factors.展开更多
Due to their capability of fabricating geometrically complex structures,additive manufacturing(AM)techniques have provided unprecedented opportunities to produce biodegradable metallic implants—especially using Mg al...Due to their capability of fabricating geometrically complex structures,additive manufacturing(AM)techniques have provided unprecedented opportunities to produce biodegradable metallic implants—especially using Mg alloys,which exhibit appropriate mechanical properties and outstanding biocompatibility.However,many challenges hinder the fabrication of AM-processed biodegradable Mg-based implants,such as the difficulty of Mg powder preparation,powder splash,and crack formation during the AM process.In the present work,the challenges of AM-processed Mg components are analyzed and solutions to these challenges are proposed.A novel Mg-based alloy(Mg-Nd-Zn-Zr alloy,JDBM)powder with a smooth surface and good roundness was first synthesized successfully,and the AM parameters for Mg-based alloys were optimized.Based on the optimized parameters,porous JDBM scaffolds with three different architectures(biomimetic,diamond,and gyroid)were then fabricated by selective laser melting(SLM),and their mechanical properties and degradation behavior were evaluated.Finally,the gyroid scaffolds with the best performance were selected for dicalcium phosphate dihydrate(DCPD)coating treatment,which greatly suppressed the degradation rate and increased the cytocompatibility,indicating a promising prospect for clinical application as bone tissue engineering scaffolds.展开更多
We investigated the feasibility of applying polymethylmethacrylate bone cement composited with biomimetic bone-mineralizsed collagen to percutaneous kyphoplasty(PKP).We performed PKP in 95 patients diagnosed with oste...We investigated the feasibility of applying polymethylmethacrylate bone cement composited with biomimetic bone-mineralizsed collagen to percutaneous kyphoplasty(PKP).We performed PKP in 95 patients diagnosed with osteoporotic vertebral compression fracture.All patients had fractures of a single vertebral body,and they were divided randomly into control(group A,47 patients)and experimental(group B,48 patients)groups.Patients in group A were treated with acrylic cement,and those in group B were treated with acrylic cement composited with the bone graft material.All patients were evaluated by a visual analogue scale(VAS),Oswestry disability index(ODI),Cobb angle and anterior vertebral body height preoperatively,and 3 days and 3 months postoperatively.All patients successfully completed surgery and were followed up thereafter.The VAS score,ODI index,Cobb angle and anterior vertebral body height compression rate in both groups had significant changes(P<0.05)preoperatively,and at 3 days and 3 months postoperatively.There was no significant difference between the two groups at different times(P>0.05).The analgesic effects of bone cement composited with bone-mineralized collagen are similar to those of bone cement only.Mineralized collagen has excellent promotion prospects by inducing new bone formation and reducing the incidence of adverse reactions caused by bone cement.展开更多
Polymeric hydrogels are fascinating platforms as 3D scaffolds for tissue repair and delivery systems of therapeutic molecules and cells.Among others,methacrylated gelatin(GelMA)has become a representative hydrogel for...Polymeric hydrogels are fascinating platforms as 3D scaffolds for tissue repair and delivery systems of therapeutic molecules and cells.Among others,methacrylated gelatin(GelMA)has become a representative hydrogel formulation,finding various biomedical applications.Recent efforts on GelMA-based hydrogels have been devoted to combining them with bioactive and functional nanomaterials,aiming to provide enhanced physicochemical and biological properties to GelMA.The benefits of this approach are multiple:i)reinforcing mechanical properties,ii)modulating viscoelastic property to allow 3D printability of bio-inks,iii)rendering electrical/magnetic property to produce electro-/magneto-active hydrogels for the repair of specific tissues(e.g.,muscle,nerve),iv)providing stimuli-responsiveness to actively deliver therapeutic molecules,and v)endowing therapeutic capacity in tissue repair process(e.g.,antioxidant effects).The nanomaterial-combined GelMA systems have shown significantly enhanced and extraordinary behaviors in various tissues(bone,skin,cardiac,and nerve)that are rarely observable with GelMA.Here we systematically review these recent efforts in nanomaterials-combined GelMA hydrogels that are considered as next-generation multifunctional platforms for tissue therapeutics.The approaches used in GelMA can also apply to other existing polymeric hydrogel systems.展开更多
Stenting is currently the major therapeutic treatment for cardiovascular diseases.However,the nonbiogenic metal stents are inclined to trigger a cascade of cellular and molecular events including inflammatory response...Stenting is currently the major therapeutic treatment for cardiovascular diseases.However,the nonbiogenic metal stents are inclined to trigger a cascade of cellular and molecular events including inflammatory response,thrombogenic reactions,smooth muscle cell hyperproliferation accompanied by the delayed arterial healing,and poor reendothelialization,thus leading to restenosis along with late stent thrombosis.To address prevalence critical problems,we present an endothelium-mimicking coating capable of rapid regeneration of a competently functioning new endothelial layer on stents through a stepwise metal(copper)-catechol-(amine)(MCA)surface chemistry strategy,leading to combinatorial endothelium-like functions with glutathione peroxidase-like catalytic activity and surface heparinization.Apart from the stable nitric oxide(NO)generating rate at the physiological level(2:2×10^(-10) mol/cm^(2)/min lasting for 60 days),this proposed strategy could also generate abundant amine groups for allowing a high heparin conjugation efficacy up to∼1μg/cm^(2),which is considerably higher than most of the conventional heparinized surfaces.The resultant coating could create an ideal microenvironment for bringing in enhanced antithrombogenicity,anti-inflammation,anti-proliferation of smooth muscle cells,re-endothelialization by regulating relevant gene expressions,hence preventing restenosis in vivo.We envision that the stepwise MCA coating strategy would facilitate the surface endothelium-mimicking engineering of vascular stents and be therefore helpful in the clinic to reduce complications associated with stenosis.展开更多
Due to the limitations in autogenous nerve grafting or Schwann cell transplantation,large gap peripheral nerve injuries require a bridging strategy supported by nerve conduit.Cell based therapies provide a novel treat...Due to the limitations in autogenous nerve grafting or Schwann cell transplantation,large gap peripheral nerve injuries require a bridging strategy supported by nerve conduit.Cell based therapies provide a novel treatment for peripheral nerve injuries.In this study,we first experimented an optimal scaffold material synthesis protocol,from where we selected the 10%GFD formula(10%GelMA hydrogel,recombinant human basic fibroblast growth factor and dental pulp stem cells(DPSCs))to fill a cellulose/soy protein isolate composite membrane(CSM)tube to construct a third generation of nerve regeneration conduit,CSM-GFD.Then this CSM-GFD conduit was applied to repair a 15-mm long defect of sciatic nerve in a rat model.After 12 week post implant surgery,at histologic level,we found CSM-GFD conduit could regenerate nerve tissue like neuron and Schwann like nerve cells and myelinated nerve fibers.At physical level,CSM-GFD achieved functional recovery assessed by a sciatic functional index study.In both levels,CSM-GFD performed like what gold standard,the nerve autograft,could do.Further,we unveiled that almost all newly formed nerve tissue at defect site was originated from the direct differentiation of exogeneous DPSCs in CSM-GFD.In conclusion,we claimed that this third-generation nerve regeneration conduit,CSM-GFD,could be a promising tissue engineering approach to replace the conventional nerve autograft to treat the large gap defect in peripheral nerve injuries.展开更多
This review focusses on the application of physiological conditions for the mechanistic understanding of magnesium degradation.Despite the undisputed relevance of simplified laboratory setups for alloy screening purpo...This review focusses on the application of physiological conditions for the mechanistic understanding of magnesium degradation.Despite the undisputed relevance of simplified laboratory setups for alloy screening purposes,realistic and predictive in vitro setups are needed.Due to the complexity of these systems,the review gives an overview about technical measures,defines some caveats and can be used as a guideline for the establishment of harmonized laboratory approaches.展开更多
Canine parvovirus type 2(CPV-2) infection is the most lethal disease of dogs with higher mortality in puppies worldwide.In today’s world,dogs are an integral part of our communities as well as dogs breeding and reari...Canine parvovirus type 2(CPV-2) infection is the most lethal disease of dogs with higher mortality in puppies worldwide.In today’s world,dogs are an integral part of our communities as well as dogs breeding and rearing has become a lucrative business.Therefore,a fast,accurate,portable,and costeffective CPV-2 detection method with the ability for on-site detection is highly desired.In this study,we for the first time proposed a nanosystem for CPV-2 DNA detection with RNA-guided RNA endonuclease Cas13 a,which upon activation results in collateral RNA degradation.We expressed LwCasl3 a in prokaryotic expression system and purified it through nickel column.Activity of Cas13 a was verified by RNA-bound fluorescent group while using a quenched fluorescent probe as signals.Further Cas13 a was combined with Recombinase polymerase amplification(RPA) and T7 transcription to establish molecular detection system termed specific high-sensitivity enzymatic reporter un-locking(SHERLOCK) for sensitive detection of CPV-2 DNA.This nanosystem can detect 100 amol/L CPV-2 DNA within 30 min.The proposed nanosystem exhibited high specificity when tested for CPV-2 and other dog viruses.This CRISPR-Cas13 a mediated sensitive detection approach can be of formidable advantage during CPV-2 outbreaks because it is time-efficient,less laborious and does not involve the use of sophisticated instruments.展开更多
Hydrogels are three-dimensional platforms that serve as substitutes for native extracellular matrix.These materials are starting to play important roles in regenerative medicine because of their similarities to native...Hydrogels are three-dimensional platforms that serve as substitutes for native extracellular matrix.These materials are starting to play important roles in regenerative medicine because of their similarities to native matrix in water content and flexibility.It would be very advantagoues for researchers to be able to regulate cell behavior and fate with specific hydrogels that have tunable mechanical properties as biophysical cues.Recent developments in dynamic chemistry have yielded designs of adaptable hydrogels that mimic dynamic nature of extracellular matrix.The current review provides a comprehensive overview for adaptable hydrogel in regenerative medicine as follows.First,we outline strategies to design adaptable hydrogel network with reversible linkages according to previous findings in supramolecular chemistry and dynamic covalent chemistry.Next,we describe the mechanism of dynamic mechanical microenvironment influence cell behaviors and fate,including how stress relaxation influences on cell behavior and how mechanosignals regulate matrix remodeling.Finally,we highlight techniques such as bioprinting which utilize adaptable hydrogel in regenerative medicine.We conclude by discussing the limitations and challenges for adaptable hydrogel,and we present perspectives for future studies.展开更多
Therapeutic proteins and peptides have revolutionized treatment for a number of diseases, and the expected increase in macromolecule-based therapies brings a new set of challenges for the pharmaceutics field. Due to t...Therapeutic proteins and peptides have revolutionized treatment for a number of diseases, and the expected increase in macromolecule-based therapies brings a new set of challenges for the pharmaceutics field. Due to their poor stability, large molecular weight, and poor transport properties,therapeutic proteins and peptides are predominantly limited to parenteral administration. The short serum half-lives typically require frequent injections to maintain an effective dose, and patient compliance is a growing issue as therapeutic protein treatments become more widely available. A number of studies have underscored the relationship of subcutaneous injections with patient non-adherence, estimating that over half of insulin-dependent adults intentionally skip injections. The development of oral formulations has the potential to address some issues associated with non-adherence including the interference with daily activities, embarrassment, and injection pain. Oral delivery can also help to eliminate the adverse effects and scar tissue buildup associated with repeated injections. However, there are several major challenges associated with oral delivery of proteins and peptides, such as the instability in the gastrointestinal(GI)tract, low permeability, and a narrow absorption window in the intestine. This review provides a detailed overview of the oral delivery route and associated challenges. Recent advances in formulation and drugdelivery technologies to enhance bioavailability are discussed, including the co-administration of compounds to alter conditions in the GI tract, the modification of the macromolecule physicochemical properties, and the use of improved targeted and controlled release carriers.展开更多
Mesenchymal stem cells(MSCs)are self-renewing,multipotent cells that could differentiate into multiple tissues.MSC-based therapy has become an attractive and promising strategy for treating human diseases through immu...Mesenchymal stem cells(MSCs)are self-renewing,multipotent cells that could differentiate into multiple tissues.MSC-based therapy has become an attractive and promising strategy for treating human diseases through immune regulation and tissue repair.However,accumulating data have indicated that MSC-based therapeutic effects are mainly attributed to the properties of the MSC-sourced secretome,especially small extracellular vesicles(sEVs).sEVs are signaling vehicles in intercellular communication in normal or pathological conditions.sEVs contain natural contents,such as proteins,mRNA,and microRNAs,and transfer these functional contents to adjacent cells or distant cells through the circulatory system.MSC-sEVs have drawn much attention as attractive agents for treating multiple diseases.The properties of MSC-sEVs include stability in circulation,good biocompatibility,and low toxicity and immunogenicity.Moreover,emerging evidence has shown that MSC-sEVs have equal or even better treatment efficacies than MSCs in many kinds of disease.This review summarizes the current research efforts on the use of MSC-sEVs in the treatment of human diseases and the existing challenges in their application from lab to clinical practice that need to be considered.展开更多
The potential applications of superparamagnetic iron oxide nanoparticles （SPIONs） in several nanomedical fields have attract- ed intense interest based on the cell-nano interaction. However, the mechanisms underlyin...The potential applications of superparamagnetic iron oxide nanoparticles （SPIONs） in several nanomedical fields have attract- ed intense interest based on the cell-nano interaction. However, the mechanisms underlying cell uptake, the intracellular trail, final fate and the biological effects of SPIONs have not yet been clearly elucidated. Here, we showed that multiple endocytic pathways were involved in the internalization process of SPIONs in the RAW264.7 macrophage. The internalized SPIONs were biocompatible and used three different metabolic pathways： The SPIONs were distributed to daughter cells during mito- sis; they were degraded in the lysosome and free iron was released into the intracellular iron metabolic pool; and, the intact SPIONs were potentially exocytosed out of the cells. The internalized SPIONs did not induce cell damage hut affected iron metabolism, inducing the upregulation of ferritin light chain at both the mRNA and protein levels and ferroportin 1 at the mRNA level. These results may contribute to the development of nanobiology and to the safe use of SPIONs in medicine when administered as a contrast medium or a drug delivery tool.展开更多
The human brain performs computations via a highly interconnected network of neurons.Taking inspiration from the information delivery and processing mechanism of the human brain in central nervous systems,bioinspired ...The human brain performs computations via a highly interconnected network of neurons.Taking inspiration from the information delivery and processing mechanism of the human brain in central nervous systems,bioinspired nanofluidic iontronics has been proposed and gradually engineered to overcome the limitations of the conventional electron-based von Neumann architecture,which shows the promising potential to enable efficient brain-like computing.Anomalous and tunable nanofluidic ion transport behaviors and spatial confinement show promising controllability of charge carriers,and a wide range of structural and chemical modification paves new ways for realizing brain-like functions.Herein,a comprehensive framework of mechanisms and design strategy is summarized to enable the rational design of nanofluidic systems and facilitate the further development of bioinspired nanofluidic iontronics.This review provides recent advances and prospects of the bioinspired nanofluidic iontronics,including ion-based brain computing,comprehension of intrinsic mechanisms,design of artificial nanochannels,and the latest artificial neuromorphic functions devices.Furthermore,the challenges and opportunities of bioinspired nanofluidic iontronics in the pioneering and interdisciplinary research fields are proposed,including brain–computer interfaces and artificial neurons.展开更多
Human beings perceive the world through the senses of sight,hearing,smell,taste,touch,space,and balance.The first five senses are prerequisites for people to live.The sensing organs upload information to the nervous s...Human beings perceive the world through the senses of sight,hearing,smell,taste,touch,space,and balance.The first five senses are prerequisites for people to live.The sensing organs upload information to the nervous systems,including the brain,for interpreting the surrounding environment.Then,the brain sends commands to muscles reflexively to react to stimuli,including light,gas,chemicals,sound,and pressure.MXene,as an emerging two-dimensional material,has been intensively adopted in the applications of various sensors and actuators.In this review,we update the sensors to mimic five primary senses and actuators for stimulating muscles,which employ MXene-based film,membrane,and composite with other functional materials.First,a brief introduction is delivered for the structure,properties,and synthesis methods of MXenes.Then,we feed the readers the recent reports on the MXene-derived image sensors as artificial retinas,gas sensors,chemical biosensors,acoustic devices,and tactile sensors for electronic skin.Besides,the actuators of MXene-based composite are introduced.Eventually,future opportunities are given to MXene research based on the requirements of artificial intelligence and humanoid robot,which may induce prospects in accompanying healthcare and biomedical engineering applications.展开更多
Bone tissue regeneration in critical-size defects is possible after implantation of a 3D scaffold and can be additionally enhanced once the scaffold is enriched with drugs or other factors supporting bone remodelling ...Bone tissue regeneration in critical-size defects is possible after implantation of a 3D scaffold and can be additionally enhanced once the scaffold is enriched with drugs or other factors supporting bone remodelling and healing.Sodium alendronate(Aln),a widely used anti-osteoporosis drug,exhibits strong inhibitory effect on bone resorption performed by osteoclasts.Thus,we propose a new approach for the treatment of bone defects in craniofacial region combining biocompatible titanium dioxide scaffolds and poly(L-lactide-co-glycolide)microparticles(MPs)loaded with Aln.The MPs were effectively attached to the surface of the scaffolds’pore walls by human recombinant collagen.Drug release from the scaffolds was characterized by initial burst(2466% of the drug released within first 24 h)followed by a sustained release phase(on average 5 mg of Aln released per day from Day 3 to Day 18).In vitro tests evidenced that Aln at concentrations of 5 and 2.5 mg/ml was not cytotoxic for MG-63 osteoblast-like cells(viability between 8166% and 9863% of control),but it prevented RANKL-induced formation of osteoclast-like cells from macrophages derived from peripheral blood mononuclear cells,as shown by reduced fusion capability and decreased tartrateresistant acid phosphatase 5b activity(5665% reduction in comparison to control after 8 days of culture).Results show that it is feasible to design the scaffolds providing required doses of Aln inhibiting osteoclastogenesis,reducing osteoclast activity,but not affecting osteoblast functions,which may be beneficial in the treatment of critical-size bone tissue defects.展开更多
Out of the wide range of calcium phosphate(CaP)biomaterials,calcium phosphate bone cements(CPCs)have attracted increased attention since their discovery in the 1980s due to their valuable properties such as bioactivit...Out of the wide range of calcium phosphate(CaP)biomaterials,calcium phosphate bone cements(CPCs)have attracted increased attention since their discovery in the 1980s due to their valuable properties such as bioactivity,osteoconductivity,injectability,hardening ability through a low-temperature setting reaction and moldability.Thereafter numerous researches have been performed to enhance the properties of CPCs.Nonetheless,low mechanical performance of CPCs limits their clinical application in load bearing regions of bone.Also,the in vivo resorption and replacement of CPC with new bone tissue is still controversial,thus further improvements of high clinical importance are required.Bioactive glasses(BGs)are biocompatible and able to bond to bone,stimulating new bone growth while dissolving over time.In the last decades extensive research has been performed analyzing the role of BGs in combination with different CaPs.Thus,the focal point of this review paper is to summarize the available research data on how injectable CPC properties could be improved or affected by the addition of BG as a secondary powder phase.It was found that despite the variances of setting time and compressive strength results,desirable injectable properties of bone cements can be achieved by the inclusion of BGs into CPCs.The published data also revealed that the degradation rate of CPCs is significantly improved by BG addition.Moreover,the presence of BG in CPCs improves the in vitro osteogenic differentiation and cell response as well as the tissue-material interaction in vivo.展开更多
The global trend toward aging populations has resulted in an increase in the occurrence of Alzheimer's disease(AD)and associated socioeconomic burdens.Abnormal metabolism of amyloid-β(Aβ)has been proposed as a s...The global trend toward aging populations has resulted in an increase in the occurrence of Alzheimer's disease(AD)and associated socioeconomic burdens.Abnormal metabolism of amyloid-β(Aβ)has been proposed as a significant pathomechanism in AD,supported by results of recent clinical trials using anti-Aβantibodies.Nonetheless,the cognitive benefits of the current treatments are limited.The etiology of AD is multifactorial,encompassing Aβand tau accumulation,neuroinflammation,demyelination,vascular dysfunction,and comorbidities,which collectively lead to widespread neurodegeneration in the brain and cognitive impairment.Hence,solely removing Aβfrom the brain may be insufficient to combat neurodegeneration and preserve cognition.To attain effective treatment for AD,it is necessary to(1)conduct extensive research on various mechanisms that cause neurodegeneration,including advances in neuroimaging techniques for earlier detection and a more precise characterization of molecular events at scales ranging from cellular to the full system level;(2)identify neuroprotective intervention targets against different neurodegeneration mechanisms;and(3)discover novel and optimal combinations of neuroprotective intervention strategies to maintain cognitive function in AD patients.The Alzheimer's Disease Neuroprotection Research Initiative's objective is to facilitate coordinated,multidisciplinary efforts to develop systemic neuroprotective strategies to combat AD.The aim is to achieve mitigation of the full spectrum of pathological processes underlying AD,with the goal of halting or even reversing cognitive decline.展开更多
Layered double hydroxides(LDHs)are widely studied to enhance corrosion resistance and biocompatibility of Mg alloys,which are promising bone implants.However,the influence of LDH coating on the osteointegration of Mg ...Layered double hydroxides(LDHs)are widely studied to enhance corrosion resistance and biocompatibility of Mg alloys,which are promising bone implants.However,the influence of LDH coating on the osteointegration of Mg implants lacks of a systematic study.In this work,Mg-Al LDH coating was prepared on pure Mg via hydrothermal treatment.The as-prepared Mg-Al LDH coated Mg exhibited better in vitro and in vivo corrosion resistance than bare Mg and Mg(OH)2 coated Mg.In vitro culture of mouse osteoblast cell line(MC3T3-E1)suggested that Mg-Al LDH coated Mg was more favorable for its osteogenic differentiation.In vitro culture of HUVECs revealed that cells cultured in the extract of Mg-Al LDH coated Mg showed superior angiogenic behaviors.More importantly,the immune response of Mg-Al LDH coated Mg was studied by in vitro culturing murine-derived macrophage cell line(RAW264.7).The results verified that Mg-Al LDH coated Mg could induce macrophage polarize to M2 phenotype(anti-inflammatory).Furthermore,the secreted factor in the macrophageconditioned culture medium of Mg-Al LDH group was more suitable for the bone differentiation of rat bone marrow stem cells(rBMSCs)and the angiogenic behavior of human umbilical vein endothelial cells(HUVECs).Finally,the result of femoral implantation suggested that Mg-Al LDH coated Mg exhibited better osteointegration than bare Mg and Mg(OH)2 coated Mg.With favorable in vitro and in vivo performances,Mg-Al LDH is promising as protective coating on Mg for orthopedic applications.展开更多
文摘May-Thurner syndrome(MTS) is the pathologic compression of the left common iliac vein by the right common iliac artery, resulting in left lower extremity pain, swelling, and deep venous thrombosis. Though this syndrome was first described in 1851, there are currently no standardized criteria to establish the diagnosis of MTS. Since MTS is treated by a wide array of specialties, including interventional radiology, vascular surgery, cardiology, and vascular medicine, the need for an established diagnostic criterion is imperative in order to reduce misdiagnosis and inappropriate treatment. Although MTS has historically been diagnosed by the presence of pathologic features, the use of dynamic imaging techniques has led to a more radiologic based diagnosis. Thus, imaging plays an integral part in screening patients for MTS, and the utility of a wide array of imaging modalities has been evaluated. Here, we summarize the historical aspects of the clinical features of this syndrome. We then provide a comprehensive assessment of the literature on the efficacy of imaging tools available to diagnose MTS. Lastly, we provide clinical pearls and recommendations to aid physicians in diagnosing the syndrome through the use of provocative measures.
基金supported by the National Natural Science Foundation of China(51571134)the SDUST Research Fund(2014TDJH104).
文摘Protein exerts a critical influence on the degradation behavior of absorbable magnesium(Mg)-based implants.However,the interaction mechanism between protein and a micro-arc oxidation(MAO)coating on Mg alloys remains unclear.Hereby,a MAO coating was fabricated on AZ31 Mg alloy.And its degradation behavior in phosphate buffer saline(PBS)containing bovine serum albumin(BSA)was investigated and compared with that of the uncoated alloy.Surface morphologies and chemical compositions were studied using Field-emission scanning electron microscope(FE-SEM),Fourier transform infrared spectrophotometer(FT-IR)and X-ray diffraction(XRD).The degradation behavior of the bare Mg alloy and its MAO coating was studied through electrochemical and hydrogen evolution tests.Cytotoxicity assay was applied to evaluate the biocompatibility of Mg alloy substrate and MAO coating.Results indicated that the presence of BSA decreased the degradation rate of Mg alloy substrate because BSA(RCH(NH2)COO‾)molecules combined with Mg2+ions to form(RCH(NH2)COO)2Mg and thus inhibited the dissolution of Mg(OH)2 by impeding the attack of Cl‾ions.In the case of MAO coated Mg alloy,the adsorption of BSA on MAO coating and the formation of(RCH(NH2)COO)2Mg exhibited a synergistic effect and enhanced the corrosion resistance of the coated alloy significantly.Furthermore,cell bioactive assay suggested that the MAO coating had good viability for MG63 cells due to its high surface area.
基金This work was supported by the National Institutes of Health Grant R01-EB022025the UT-Portugal Collaborative Research program(CoLAB)Intelligent scaffolds for molecular recognition of advanced applications in regenerative medicine.
文摘In recent years,bone tissue engineering has emerged as a promising solution to the limitations of current gold standard treatment options for bone related-disorders such as bone grafts.Bone tissue engineering provides a scaffold design that mimics the extracellular matrix,providing an architecture that guides the natural bone regeneration process.During this period,a new generation of bone tissue engineering scaffolds has been designed and characterized that explores the incorporation of signaling molecules in order to enhance cell recruitment and ingress into the scaffold,as well as osteogenic differentiation and angiogenesis,each of which is crucial to successful bone regeneration.Here,we outline and critically analyze key characteristics of successful bone tissue engineering scaffolds.We also explore candidate materials used to fabricate these scaffolds.Different growth factors involved in the highly coordinated process of bone repair are discussed,and the key requirements of a growth factor delivery system are described.Finally,we concentrate on an analysis of scaffold-based growth factor delivery strategies found in the recent literature.In particular,the incorporation of two-phase systems consisting of growth factor-loaded nanoparticles embedded into scaffolds shows great promise,both by providing sustained release over a therapeutically relevant timeframe and the potential to sequentially deliver multiple growth factors.
基金This work was supported by the National Natural Science Foundation of China(51571143)the National Key Research and Development Program of China(2016YFC1102103)+1 种基金the Science and Technology Commission of Shanghai Municipality(19441906300,18441908000,and 17440730700)San-Ming Project of Medicine in Shenzhen(SZSM201612092).
文摘Due to their capability of fabricating geometrically complex structures,additive manufacturing(AM)techniques have provided unprecedented opportunities to produce biodegradable metallic implants—especially using Mg alloys,which exhibit appropriate mechanical properties and outstanding biocompatibility.However,many challenges hinder the fabrication of AM-processed biodegradable Mg-based implants,such as the difficulty of Mg powder preparation,powder splash,and crack formation during the AM process.In the present work,the challenges of AM-processed Mg components are analyzed and solutions to these challenges are proposed.A novel Mg-based alloy(Mg-Nd-Zn-Zr alloy,JDBM)powder with a smooth surface and good roundness was first synthesized successfully,and the AM parameters for Mg-based alloys were optimized.Based on the optimized parameters,porous JDBM scaffolds with three different architectures(biomimetic,diamond,and gyroid)were then fabricated by selective laser melting(SLM),and their mechanical properties and degradation behavior were evaluated.Finally,the gyroid scaffolds with the best performance were selected for dicalcium phosphate dihydrate(DCPD)coating treatment,which greatly suppressed the degradation rate and increased the cytocompatibility,indicating a promising prospect for clinical application as bone tissue engineering scaffolds.
基金This work is in part supported by NSFC No.51402176the Inner Mongolia autonomous region natural science fund No.20070501.
文摘We investigated the feasibility of applying polymethylmethacrylate bone cement composited with biomimetic bone-mineralizsed collagen to percutaneous kyphoplasty(PKP).We performed PKP in 95 patients diagnosed with osteoporotic vertebral compression fracture.All patients had fractures of a single vertebral body,and they were divided randomly into control(group A,47 patients)and experimental(group B,48 patients)groups.Patients in group A were treated with acrylic cement,and those in group B were treated with acrylic cement composited with the bone graft material.All patients were evaluated by a visual analogue scale(VAS),Oswestry disability index(ODI),Cobb angle and anterior vertebral body height preoperatively,and 3 days and 3 months postoperatively.All patients successfully completed surgery and were followed up thereafter.The VAS score,ODI index,Cobb angle and anterior vertebral body height compression rate in both groups had significant changes(P<0.05)preoperatively,and at 3 days and 3 months postoperatively.There was no significant difference between the two groups at different times(P>0.05).The analgesic effects of bone cement composited with bone-mineralized collagen are similar to those of bone cement only.Mineralized collagen has excellent promotion prospects by inducing new bone formation and reducing the incidence of adverse reactions caused by bone cement.
基金supported by the grants(2015K1A1A2032163,2020R1I1A1A01071828,2018K1A4A3A01064257,2021R1A5A2022318,2018R1D1A1B07048020),National Research Foundation(NRF),Republic of Korea.
文摘Polymeric hydrogels are fascinating platforms as 3D scaffolds for tissue repair and delivery systems of therapeutic molecules and cells.Among others,methacrylated gelatin(GelMA)has become a representative hydrogel formulation,finding various biomedical applications.Recent efforts on GelMA-based hydrogels have been devoted to combining them with bioactive and functional nanomaterials,aiming to provide enhanced physicochemical and biological properties to GelMA.The benefits of this approach are multiple:i)reinforcing mechanical properties,ii)modulating viscoelastic property to allow 3D printability of bio-inks,iii)rendering electrical/magnetic property to produce electro-/magneto-active hydrogels for the repair of specific tissues(e.g.,muscle,nerve),iv)providing stimuli-responsiveness to actively deliver therapeutic molecules,and v)endowing therapeutic capacity in tissue repair process(e.g.,antioxidant effects).The nanomaterial-combined GelMA systems have shown significantly enhanced and extraordinary behaviors in various tissues(bone,skin,cardiac,and nerve)that are rarely observable with GelMA.Here we systematically review these recent efforts in nanomaterials-combined GelMA hydrogels that are considered as next-generation multifunctional platforms for tissue therapeutics.The approaches used in GelMA can also apply to other existing polymeric hydrogel systems.
基金This work was supported by the National Natural Science Foundation of China(31570957)International Cooperation Project by the Science and Technology Department of Sichuan Province(2019YFH0103)+1 种基金Early Career Researcher Development Scheme 2017 of Institute of Health and Biomedical Innovation,Queensland University of Technology and International Team for Implantology Research Grant(1260_2017)Applied Basic Research Project funded by Sichuan Provincial Science and Technology Department(2017JY0296).
文摘Stenting is currently the major therapeutic treatment for cardiovascular diseases.However,the nonbiogenic metal stents are inclined to trigger a cascade of cellular and molecular events including inflammatory response,thrombogenic reactions,smooth muscle cell hyperproliferation accompanied by the delayed arterial healing,and poor reendothelialization,thus leading to restenosis along with late stent thrombosis.To address prevalence critical problems,we present an endothelium-mimicking coating capable of rapid regeneration of a competently functioning new endothelial layer on stents through a stepwise metal(copper)-catechol-(amine)(MCA)surface chemistry strategy,leading to combinatorial endothelium-like functions with glutathione peroxidase-like catalytic activity and surface heparinization.Apart from the stable nitric oxide(NO)generating rate at the physiological level(2:2×10^(-10) mol/cm^(2)/min lasting for 60 days),this proposed strategy could also generate abundant amine groups for allowing a high heparin conjugation efficacy up to∼1μg/cm^(2),which is considerably higher than most of the conventional heparinized surfaces.The resultant coating could create an ideal microenvironment for bringing in enhanced antithrombogenicity,anti-inflammation,anti-proliferation of smooth muscle cells,re-endothelialization by regulating relevant gene expressions,hence preventing restenosis in vivo.We envision that the stepwise MCA coating strategy would facilitate the surface endothelium-mimicking engineering of vascular stents and be therefore helpful in the clinic to reduce complications associated with stenosis.
基金supported by the National Natural Science Funding of China(81701032,81871503)the Wenzhou Science and Technology Association Project,the Wenzhou Major Scientific and Technological Innovation Key Medical and Health Project(ZY2019010)+4 种基金the Wenzhou Medical University grant(QTJ16026)Wenzhou Science and Technology Association Project,Wenzhou Basic Research Project(Y20180131)Zhejiang Province Program of the Medical and Health Science and Technology(2018KY537)Zhejiang Natural Science Foundation(LGF18C100002)Zhejiang Xinmiao Talents Program(2018R413186).
文摘Due to the limitations in autogenous nerve grafting or Schwann cell transplantation,large gap peripheral nerve injuries require a bridging strategy supported by nerve conduit.Cell based therapies provide a novel treatment for peripheral nerve injuries.In this study,we first experimented an optimal scaffold material synthesis protocol,from where we selected the 10%GFD formula(10%GelMA hydrogel,recombinant human basic fibroblast growth factor and dental pulp stem cells(DPSCs))to fill a cellulose/soy protein isolate composite membrane(CSM)tube to construct a third generation of nerve regeneration conduit,CSM-GFD.Then this CSM-GFD conduit was applied to repair a 15-mm long defect of sciatic nerve in a rat model.After 12 week post implant surgery,at histologic level,we found CSM-GFD conduit could regenerate nerve tissue like neuron and Schwann like nerve cells and myelinated nerve fibers.At physical level,CSM-GFD achieved functional recovery assessed by a sciatic functional index study.In both levels,CSM-GFD performed like what gold standard,the nerve autograft,could do.Further,we unveiled that almost all newly formed nerve tissue at defect site was originated from the direct differentiation of exogeneous DPSCs in CSM-GFD.In conclusion,we claimed that this third-generation nerve regeneration conduit,CSM-GFD,could be a promising tissue engineering approach to replace the conventional nerve autograft to treat the large gap defect in peripheral nerve injuries.
基金We would like to thank the China Scholarship Council(CSC)for a scholarship to RQHThe research leading to these results has received funding from the Helmholtz Virtual Institute“In vivo studies of biodegradable magnesium based implant materials(MetBioMat)”under grant agreement no VH-VI-523.
文摘This review focusses on the application of physiological conditions for the mechanistic understanding of magnesium degradation.Despite the undisputed relevance of simplified laboratory setups for alloy screening purposes,realistic and predictive in vitro setups are needed.Due to the complexity of these systems,the review gives an overview about technical measures,defines some caveats and can be used as a guideline for the establishment of harmonized laboratory approaches.
基金supported by the National Key Research and Development Program of China (No.2017YFA0205301)National Natural Science Foundation of China (Nos.81902153,61527806 and 81430055)+2 种基金Key Research and Development Project of Jiangsu Province (No.BE2019761)Programs for Changjiang Scholars and Innovative Research Team in University (No.IRT_15R13)open Funding of State Key Laboratory of Oral Diseases (No.SKLOD20190F03)
文摘Canine parvovirus type 2(CPV-2) infection is the most lethal disease of dogs with higher mortality in puppies worldwide.In today’s world,dogs are an integral part of our communities as well as dogs breeding and rearing has become a lucrative business.Therefore,a fast,accurate,portable,and costeffective CPV-2 detection method with the ability for on-site detection is highly desired.In this study,we for the first time proposed a nanosystem for CPV-2 DNA detection with RNA-guided RNA endonuclease Cas13 a,which upon activation results in collateral RNA degradation.We expressed LwCasl3 a in prokaryotic expression system and purified it through nickel column.Activity of Cas13 a was verified by RNA-bound fluorescent group while using a quenched fluorescent probe as signals.Further Cas13 a was combined with Recombinase polymerase amplification(RPA) and T7 transcription to establish molecular detection system termed specific high-sensitivity enzymatic reporter un-locking(SHERLOCK) for sensitive detection of CPV-2 DNA.This nanosystem can detect 100 amol/L CPV-2 DNA within 30 min.The proposed nanosystem exhibited high specificity when tested for CPV-2 and other dog viruses.This CRISPR-Cas13 a mediated sensitive detection approach can be of formidable advantage during CPV-2 outbreaks because it is time-efficient,less laborious and does not involve the use of sophisticated instruments.
基金support of the National Key Research and Development Program of China(2016YFE0132700)National Natural Science Foundation of China(51822306,51673171)+1 种基金Science Technology Department of Zhejiang Province(2020C03042)the Fundamental Research Funds for the Central Universities of China.
文摘Hydrogels are three-dimensional platforms that serve as substitutes for native extracellular matrix.These materials are starting to play important roles in regenerative medicine because of their similarities to native matrix in water content and flexibility.It would be very advantagoues for researchers to be able to regulate cell behavior and fate with specific hydrogels that have tunable mechanical properties as biophysical cues.Recent developments in dynamic chemistry have yielded designs of adaptable hydrogels that mimic dynamic nature of extracellular matrix.The current review provides a comprehensive overview for adaptable hydrogel in regenerative medicine as follows.First,we outline strategies to design adaptable hydrogel network with reversible linkages according to previous findings in supramolecular chemistry and dynamic covalent chemistry.Next,we describe the mechanism of dynamic mechanical microenvironment influence cell behaviors and fate,including how stress relaxation influences on cell behavior and how mechanosignals regulate matrix remodeling.Finally,we highlight techniques such as bioprinting which utilize adaptable hydrogel in regenerative medicine.We conclude by discussing the limitations and challenges for adaptable hydrogel,and we present perspectives for future studies.
基金supported in part by a grant from the National Institutes of Health (R01-EB-00246020)the Cockrell Family Regents Chair. Angela M.Wagner was supported by a National Science Foundation Graduate Research Fellowship (DGE-1610403)+1 种基金the S.E.S.H.A. Endowed Graduate Fellowship in Engineeringthe Philanthropic Educational Organization Scholar Award
文摘Therapeutic proteins and peptides have revolutionized treatment for a number of diseases, and the expected increase in macromolecule-based therapies brings a new set of challenges for the pharmaceutics field. Due to their poor stability, large molecular weight, and poor transport properties,therapeutic proteins and peptides are predominantly limited to parenteral administration. The short serum half-lives typically require frequent injections to maintain an effective dose, and patient compliance is a growing issue as therapeutic protein treatments become more widely available. A number of studies have underscored the relationship of subcutaneous injections with patient non-adherence, estimating that over half of insulin-dependent adults intentionally skip injections. The development of oral formulations has the potential to address some issues associated with non-adherence including the interference with daily activities, embarrassment, and injection pain. Oral delivery can also help to eliminate the adverse effects and scar tissue buildup associated with repeated injections. However, there are several major challenges associated with oral delivery of proteins and peptides, such as the instability in the gastrointestinal(GI)tract, low permeability, and a narrow absorption window in the intestine. This review provides a detailed overview of the oral delivery route and associated challenges. Recent advances in formulation and drugdelivery technologies to enhance bioavailability are discussed, including the co-administration of compounds to alter conditions in the GI tract, the modification of the macromolecule physicochemical properties, and the use of improved targeted and controlled release carriers.
基金Supported by National Natural Science Foundation of China,No.81971878Opening Project of Military Logistics,No.BLB19J006and Tianjin University Independent Innovation Fund,No.2020XRG-0027,No.2020XYF-0041,and No.2020XZY-0086.
文摘Mesenchymal stem cells(MSCs)are self-renewing,multipotent cells that could differentiate into multiple tissues.MSC-based therapy has become an attractive and promising strategy for treating human diseases through immune regulation and tissue repair.However,accumulating data have indicated that MSC-based therapeutic effects are mainly attributed to the properties of the MSC-sourced secretome,especially small extracellular vesicles(sEVs).sEVs are signaling vehicles in intercellular communication in normal or pathological conditions.sEVs contain natural contents,such as proteins,mRNA,and microRNAs,and transfer these functional contents to adjacent cells or distant cells through the circulatory system.MSC-sEVs have drawn much attention as attractive agents for treating multiple diseases.The properties of MSC-sEVs include stability in circulation,good biocompatibility,and low toxicity and immunogenicity.Moreover,emerging evidence has shown that MSC-sEVs have equal or even better treatment efficacies than MSCs in many kinds of disease.This review summarizes the current research efforts on the use of MSC-sEVs in the treatment of human diseases and the existing challenges in their application from lab to clinical practice that need to be considered.
基金supported by the National Basic Research Program of China,Ministry of Science and Technology of China (Grant Nos. 2006CB933202 and 2011CB933504) the National High Technology Research and Development Program of China (Grant No. 2008AA02Z425)a grant from the National Natural Science Foundation of China (Grant No.81071072)
文摘The potential applications of superparamagnetic iron oxide nanoparticles （SPIONs） in several nanomedical fields have attract- ed intense interest based on the cell-nano interaction. However, the mechanisms underlying cell uptake, the intracellular trail, final fate and the biological effects of SPIONs have not yet been clearly elucidated. Here, we showed that multiple endocytic pathways were involved in the internalization process of SPIONs in the RAW264.7 macrophage. The internalized SPIONs were biocompatible and used three different metabolic pathways： The SPIONs were distributed to daughter cells during mito- sis; they were degraded in the lysosome and free iron was released into the intracellular iron metabolic pool; and, the intact SPIONs were potentially exocytosed out of the cells. The internalized SPIONs did not induce cell damage hut affected iron metabolism, inducing the upregulation of ferritin light chain at both the mRNA and protein levels and ferroportin 1 at the mRNA level. These results may contribute to the development of nanobiology and to the safe use of SPIONs in medicine when administered as a contrast medium or a drug delivery tool.
基金supported by the National Natural Science Foundation of China(Nos.21975209,52273305,22205185,52025132,T2241022,21621091,22021001,and 22121001)the 111 Project(Nos.B17027 and B16029)+2 种基金the National Science Foundation of Fujian Province of China(No.2022J02059)the Science and Technology Projects of Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province(No.RD2022070601)the Tencent Foundation(The XPLORER PRIZE).
文摘The human brain performs computations via a highly interconnected network of neurons.Taking inspiration from the information delivery and processing mechanism of the human brain in central nervous systems,bioinspired nanofluidic iontronics has been proposed and gradually engineered to overcome the limitations of the conventional electron-based von Neumann architecture,which shows the promising potential to enable efficient brain-like computing.Anomalous and tunable nanofluidic ion transport behaviors and spatial confinement show promising controllability of charge carriers,and a wide range of structural and chemical modification paves new ways for realizing brain-like functions.Herein,a comprehensive framework of mechanisms and design strategy is summarized to enable the rational design of nanofluidic systems and facilitate the further development of bioinspired nanofluidic iontronics.This review provides recent advances and prospects of the bioinspired nanofluidic iontronics,including ion-based brain computing,comprehension of intrinsic mechanisms,design of artificial nanochannels,and the latest artificial neuromorphic functions devices.Furthermore,the challenges and opportunities of bioinspired nanofluidic iontronics in the pioneering and interdisciplinary research fields are proposed,including brain–computer interfaces and artificial neurons.
基金the National Natural Science Foundation of China(No.51802116)the Natural Science Foundation of Shandong Province for the Natural Science Fund for Excellent Young Scholars of Shandong Province(No.ZR202112010179)+9 种基金the Doctoral Fund(No.ZR2019BEM040)H.L.acknowledges the“20 Items of University”Project of Jinan(No.2018GXRC031)W.Z.thanks the Major Scientific and Technological Innovation Project of Shandong Province(No.2021CXGC010603)the National Natural Science Foundation of China(No.52022037)Taishan Scholars Project Special Funds(No.TSQN201812083)supported by the Foundation(No.GZKF202107)of State Key Laboratory of Biobased Material and Green Papermaking,Qilu University of Technology,Shandong Academy of Sciencesthe National Natural Science Foundation of China(No.22003074)the National Natural Science Foundation of China(No.52071225)the National Science Center and the Czech Republic under the European Regional Development Fund(ERDF)program“Institute of Environmental Technology-Excellent Research”(No.CZ.02.1.01/0.0/0.0/16_019/0000853)the Sino-German Research Institute for support(No.GZ 1400).
文摘Human beings perceive the world through the senses of sight,hearing,smell,taste,touch,space,and balance.The first five senses are prerequisites for people to live.The sensing organs upload information to the nervous systems,including the brain,for interpreting the surrounding environment.Then,the brain sends commands to muscles reflexively to react to stimuli,including light,gas,chemicals,sound,and pressure.MXene,as an emerging two-dimensional material,has been intensively adopted in the applications of various sensors and actuators.In this review,we update the sensors to mimic five primary senses and actuators for stimulating muscles,which employ MXene-based film,membrane,and composite with other functional materials.First,a brief introduction is delivered for the structure,properties,and synthesis methods of MXenes.Then,we feed the readers the recent reports on the MXene-derived image sensors as artificial retinas,gas sensors,chemical biosensors,acoustic devices,and tactile sensors for electronic skin.Besides,the actuators of MXene-based composite are introduced.Eventually,future opportunities are given to MXene research based on the requirements of artificial intelligence and humanoid robot,which may induce prospects in accompanying healthcare and biomedical engineering applications.
基金supported by National Science Centre,Poland(2013/09/N/ST8/00309)Norwegian Research Council(228415)BMBF,Germany(GoBone German-Polish bilateral project 01DS16010A).
文摘Bone tissue regeneration in critical-size defects is possible after implantation of a 3D scaffold and can be additionally enhanced once the scaffold is enriched with drugs or other factors supporting bone remodelling and healing.Sodium alendronate(Aln),a widely used anti-osteoporosis drug,exhibits strong inhibitory effect on bone resorption performed by osteoclasts.Thus,we propose a new approach for the treatment of bone defects in craniofacial region combining biocompatible titanium dioxide scaffolds and poly(L-lactide-co-glycolide)microparticles(MPs)loaded with Aln.The MPs were effectively attached to the surface of the scaffolds’pore walls by human recombinant collagen.Drug release from the scaffolds was characterized by initial burst(2466% of the drug released within first 24 h)followed by a sustained release phase(on average 5 mg of Aln released per day from Day 3 to Day 18).In vitro tests evidenced that Aln at concentrations of 5 and 2.5 mg/ml was not cytotoxic for MG-63 osteoblast-like cells(viability between 8166% and 9863% of control),but it prevented RANKL-induced formation of osteoclast-like cells from macrophages derived from peripheral blood mononuclear cells,as shown by reduced fusion capability and decreased tartrateresistant acid phosphatase 5b activity(5665% reduction in comparison to control after 8 days of culture).Results show that it is feasible to design the scaffolds providing required doses of Aln inhibiting osteoclastogenesis,reducing osteoclast activity,but not affecting osteoblast functions,which may be beneficial in the treatment of critical-size bone tissue defects.
基金financial support from the European Union’s Horizon 2020 research and innovation programme under the grant agreement No 857287(BBCE).
文摘Out of the wide range of calcium phosphate(CaP)biomaterials,calcium phosphate bone cements(CPCs)have attracted increased attention since their discovery in the 1980s due to their valuable properties such as bioactivity,osteoconductivity,injectability,hardening ability through a low-temperature setting reaction and moldability.Thereafter numerous researches have been performed to enhance the properties of CPCs.Nonetheless,low mechanical performance of CPCs limits their clinical application in load bearing regions of bone.Also,the in vivo resorption and replacement of CPC with new bone tissue is still controversial,thus further improvements of high clinical importance are required.Bioactive glasses(BGs)are biocompatible and able to bond to bone,stimulating new bone growth while dissolving over time.In the last decades extensive research has been performed analyzing the role of BGs in combination with different CaPs.Thus,the focal point of this review paper is to summarize the available research data on how injectable CPC properties could be improved or affected by the addition of BG as a secondary powder phase.It was found that despite the variances of setting time and compressive strength results,desirable injectable properties of bone cements can be achieved by the inclusion of BGs into CPCs.The published data also revealed that the degradation rate of CPCs is significantly improved by BG addition.Moreover,the presence of BG in CPCs improves the in vitro osteogenic differentiation and cell response as well as the tissue-material interaction in vivo.
基金National Natural Science Foundation of China,Grant/Award Numbers:92249305,82120108010,81930028,31921003Academy of Medical Sciences(Newton Advanced Fellowship),Grant/Award Number:NAF/R11/1010National Institutes of Health,Grant/Award Number:R01DA056739。
文摘The global trend toward aging populations has resulted in an increase in the occurrence of Alzheimer's disease(AD)and associated socioeconomic burdens.Abnormal metabolism of amyloid-β(Aβ)has been proposed as a significant pathomechanism in AD,supported by results of recent clinical trials using anti-Aβantibodies.Nonetheless,the cognitive benefits of the current treatments are limited.The etiology of AD is multifactorial,encompassing Aβand tau accumulation,neuroinflammation,demyelination,vascular dysfunction,and comorbidities,which collectively lead to widespread neurodegeneration in the brain and cognitive impairment.Hence,solely removing Aβfrom the brain may be insufficient to combat neurodegeneration and preserve cognition.To attain effective treatment for AD,it is necessary to(1)conduct extensive research on various mechanisms that cause neurodegeneration,including advances in neuroimaging techniques for earlier detection and a more precise characterization of molecular events at scales ranging from cellular to the full system level;(2)identify neuroprotective intervention targets against different neurodegeneration mechanisms;and(3)discover novel and optimal combinations of neuroprotective intervention strategies to maintain cognitive function in AD patients.The Alzheimer's Disease Neuroprotection Research Initiative's objective is to facilitate coordinated,multidisciplinary efforts to develop systemic neuroprotective strategies to combat AD.The aim is to achieve mitigation of the full spectrum of pathological processes underlying AD,with the goal of halting or even reversing cognitive decline.
基金the China Postdoctoral Science Foundation(2019M662830)National Natural Science Foundation of China(31771044)+2 种基金Shanghai Committee of Science and Technology,China(18410760600)International Partnership Program of Chinese Academy of Sciences Grant No.GJHZ1850,Natural Science Foundation of Guangdong Province,China(Grant No.2020A1515011447)Scientific and Technological Projects of Guangzhou,China(Grant No.202002030283).
文摘Layered double hydroxides(LDHs)are widely studied to enhance corrosion resistance and biocompatibility of Mg alloys,which are promising bone implants.However,the influence of LDH coating on the osteointegration of Mg implants lacks of a systematic study.In this work,Mg-Al LDH coating was prepared on pure Mg via hydrothermal treatment.The as-prepared Mg-Al LDH coated Mg exhibited better in vitro and in vivo corrosion resistance than bare Mg and Mg(OH)2 coated Mg.In vitro culture of mouse osteoblast cell line(MC3T3-E1)suggested that Mg-Al LDH coated Mg was more favorable for its osteogenic differentiation.In vitro culture of HUVECs revealed that cells cultured in the extract of Mg-Al LDH coated Mg showed superior angiogenic behaviors.More importantly,the immune response of Mg-Al LDH coated Mg was studied by in vitro culturing murine-derived macrophage cell line(RAW264.7).The results verified that Mg-Al LDH coated Mg could induce macrophage polarize to M2 phenotype(anti-inflammatory).Furthermore,the secreted factor in the macrophageconditioned culture medium of Mg-Al LDH group was more suitable for the bone differentiation of rat bone marrow stem cells(rBMSCs)and the angiogenic behavior of human umbilical vein endothelial cells(HUVECs).Finally,the result of femoral implantation suggested that Mg-Al LDH coated Mg exhibited better osteointegration than bare Mg and Mg(OH)2 coated Mg.With favorable in vitro and in vivo performances,Mg-Al LDH is promising as protective coating on Mg for orthopedic applications.
