The poor surface conditions and osseointegration capacity of 3D printed Ti6Al4V implants(3DPT)significantly influence their performance as orthopedic and dental implants.In this work,we creatively introduce a one-step...The poor surface conditions and osseointegration capacity of 3D printed Ti6Al4V implants(3DPT)significantly influence their performance as orthopedic and dental implants.In this work,we creatively introduce a one-step femtosecond laser treatment to improve the surface conditions and osteointegration.The surface characterization,mechanical properties,corrosion resistance,and biological responses were investigated.These results found that femtosecond laser eliminated defects like embedded powders and superficial cracks while forming the nano cones-like structures surface on 3DPT,leading to enhanced osseointegration,anti-corrosion,and anti-fatigue performance.Molecular dynamics simulations revealed the ablation removal mechanism and the formation of nano cone-like structures.These findings were further supported by the in vivo studies,showing that the FS-treated implants had superior bone-implant contact and osseointegration.Hence,the one-step femtosecond laser method is regarded as a promising surface modification method for improving the functional performance of Ti-based orthopedic implants.展开更多
Although hydrogels have demonstrated great potential as new wound dressing materials,their instability in shape and/or mechanical characteristics due to water loss or freezing remains a shortcoming for wound care appl...Although hydrogels have demonstrated great potential as new wound dressing materials,their instability in shape and/or mechanical characteristics due to water loss or freezing remains a shortcoming for wound care application.Herein,a novel injectable organohydrogel(IOH)of physically crosslinked polyvinyl alco-hol/glycerol that possesses non-drying capability and high stability at low temperature was developed for wound care.IOH has a skin-like stiffness(G’,∼280 Pa),high injectability,self-healing capability,high water-vapor transmission rate,and bacterial inhibitory effect.IOH exhibits high shape and mechanical stabilities after curing at 37°C and 50%relative humidity for 7 days or after curing at-20°C for 1 day.In addition,glycerol in IOH enabled an efficient loading and release of water-insoluble curcumin,a well-known anti-bacterial and anti-inflammation drug.The curcumin-releasing IOH(Cur-IOH)demonstrated significantly enhanced anti-bacterial performance compared to IOH or curcumin-loading polyvinyl alco-hol hydrogel.More importantly,Cur-IOH could accelerate wound healing in a murine full-thickness skin defect wound model,revealing improved wound contraction,collagen deposition,angiogenesis,and epi-dermis formation.This study demonstrates the great potential of organohydrogel for the reparation of severe wounds and Cur-IOH as a new type of injectable wound healing material.展开更多
There is a lack of effective tissue repair and regeneration strategies in current clinical practices.Numerous studies have suggested that smart or responsive biomaterials possessing the ability to respond to endogenou...There is a lack of effective tissue repair and regeneration strategies in current clinical practices.Numerous studies have suggested that smart or responsive biomaterials possessing the ability to respond to endogenous stimuli in vivo may positively mediate the tissue micro-environment towards a tissue repair or regeneration.Mechanical stimuli,which constantly exist in a wide range of biological systems and are involved in almost all the physiological processes,belong to such stimuli to which responsive biomaterials can respond.In recent studies,a new type of smart biomaterials,which can dynamically adapt to the mechanical stimuli in vivo and thus has specific functionality consistently mediated by such mechanical stimuli,has emerged.In contrast to common biomaterials that passively react to the mechanical environment of an implantation site,such mechano-active biomaterials have enabled various active or automatic strategies for tissue repair or regeneration,such as providing precise spatial-temporal controls on delivery of drugs or cells in the organs of the musculoskeletal and the circulatory systems;in situ reconstructing the original or a favorable mechanical environment at a lesion site;and accelerating the tissue remodeling or healing process via a mechanobiological effect.This article elucidates a perspective of perfecting tissue repair or regeneration using mechano-active biomaterials,especially highlighting the rationale behind the concept of mechano-active biomaterials and their potential in the repair or regeneration of musculoskeletal and cardiovascular tissues.Albeit outstanding challenges and unknowns,the emergence of mechano-active biomaterials has become a new avenue for tissue engineering and regenerative medicine.展开更多
Bacterial infection and osteogenic integration are the two main problems that cause severe complications after surgeries. In this study, the antibacterial and osteogenic properties were simultaneously introduced in bi...Bacterial infection and osteogenic integration are the two main problems that cause severe complications after surgeries. In this study, the antibacterial and osteogenic properties were simultaneously introduced in biomaterials, where copper nanoparticles(Cu NPs) were generated by in situ reductions of Cu ions into a mussel-inspired hyperbranched polyglycerol(MI-h PG) coating via a simple dip-coating method.This hyperbranched polyglycerol with 10 % catechol groups’ modification presents excellent antifouling property, which could effectively reduce bacteria adhesion on the surface. In this work, polycaprolactone(PCL) electrospun fiber membrane was selected as the substrate, which is commonly used in biomedical implants in bone regeneration and cardiovascular stents because of its good biocompatibility and easy post-modification. The as-fabricated Cu NPs-incorporated PCL membrane [PCL-(MI-h PG)-Cu NPs]was confirmed with effective antibacterial performance via in vitro antibacterial tests against Staphylococcus aureus(S. aureus), Escherichia coli(E. coli), and multi-resistant E. coli. In addition, the in vitro results demonstrated that osteogenic property of PCL-(MI-h PG)-Cu NPs was realized by upregulating the osteoblast-related gene expressions and protein activity. This study shows that antibacterial and osteogenic properties can be balanced in a surface coating by introducing Cu NPs.展开更多
Repair of severe skin tissue injury remains a great challenge and wound infection is still a formidable problem.In this study,new macroporous and antibacterial gelatin/alginate(SAG)-based hydrogels for wound repair we...Repair of severe skin tissue injury remains a great challenge and wound infection is still a formidable problem.In this study,new macroporous and antibacterial gelatin/alginate(SAG)-based hydrogels for wound repair were designed and developed based on in-situ gas foaming method and ion release strategy as a result of Mg-Cu particles degradation in the hydrogel matrix.The addition of Mg-Cu particles decreased the storage modulus of SAG,maintained its mechanical resilience and enhanced its water-absorbing capability.Moreover,the water vapor transmission rate of SAG added with 2 wt.%Mg-Cu(SAG-2 MC)was 124%of that of medical gauze and 804%of commercial Tegaderm^(TM)film dressing.The bacterial inhibition rates of SAG-2 MC against S.aureus.E.coli and P.aeruginosa reached 99.9%±0.1%,98.7%±1.2%and 98.0%±0.7%,respectively,significantly greater than those of the SAG hydrogel and Mg particle-modified hydrogels.In addition,SAG-2 MC hydrogel was biocompatible and promoted cell migration.In vivo experiment results indicated that SAG-2 MC significantly accelerated the skin wound healing in murine model as demonstrated by higher epidermis thickness,more collagen deposition and enhanced angiogenesis compared with SAG-OMC,SAG-2 M and TegadermTM film.In summary,Mg-Cu particles have great potential to modulate the physiochemical and biological properties of SAG hydrogels.Mg-Cu particle-modified SAG hydrogels reveal significant promise in the treatment of severe skin wound or other soft tissue lesions.展开更多
The fast development of both biomaterials and regulatory science calls for a convergence,which is addressed in this article via their link through medical products of biomaterials and related safety and efficacy evalu...The fast development of both biomaterials and regulatory science calls for a convergence,which is addressed in this article via their link through medical products of biomaterials and related safety and efficacy evaluation.The updated definition of biomaterials,and concepts of biomaterials-related medical products and so-called medical-grade and implantable materials are firstly introduced.Then a brief overview of the concept and history of regulatory science and its assessment of safety and efficacy of medical products,as well as the currently ongoing biomaterials-related regulatory science programs are presented.Finally,the opportunities provided by regulatory science for biomaterials as well as challenges on how to develop a biomaterials-based regulatory science system are discussed.As the first article in the field to elucidate the relationship between biomaterials and regulatory science,key take-home messages include(1)biomaterials alone are not medical products;(2)regulatory authorities approve/clear final medical products,not biomaterials;(3)there is no definition/regulation on the so-called medical-grade or implantable materials;and(4)safety and efficacy refer to final medical products,not biomaterials alone.展开更多
Despite the considerable potentiality of photodynamic therapy(PDT)in cancer treatment,conventional hydrophobic photosensitizers cause obstacles for in vivo application,while their inert structures are difficult to che...Despite the considerable potentiality of photodynamic therapy(PDT)in cancer treatment,conventional hydrophobic photosensitizers cause obstacles for in vivo application,while their inert structures are difficult to chemically modify.Additionally,undesirable tumor hypoxia resulting from oxygen consumption also discounts the therapeutic efficacy of PDT.Herein,we developed a self-strengthened nanogel with reactive oxygen species(ROS)trigger-explosive property.IR780 was spontaneous assembled within the conical cavity of cyclodextrin(β-CD)using host-vip interactions,while adjacent IR780 molecules on the dextrin backbone with hydrophobic interaction andπconjugation induced nanogel formation.Simultaneously,hydrophilic compound tirapazamine(TPZ)was incorporated into nanogel for synergistic tumor treatment.The inherent high levels of ROS in tumor can break down boronic ester bond linker of nanogel,initiating its disintegration.Furthermore,our findings indicate the ROS level(including H2O2and1O2)can be transiently enhanced during PDT process at the animal level,which accelerates the explosion of nanogel.Notably,the IR780@β-CD module exhibited enhanced ROS generation efficiency during PDT with the continues explosion of nanogel,which further strengthens nanogel disintegration,tumor phototherapy and cargo releasement.Additionally,the released TPZ is activated under hypoxic conditions after PDT treatment,addressing the limitations of PDT and facilitating multi-synergistic tumor treatment.展开更多
In neurosurgery procedures,cerebrospinal fluid leakage is a commonly encountered complication.Re-constructing skull base defects with patch materials can reduce the risk of cerebrospinal fluid leakage which can lead t...In neurosurgery procedures,cerebrospinal fluid leakage is a commonly encountered complication.Re-constructing skull base defects with patch materials can reduce the risk of cerebrospinal fluid leakage which can lead to serious issues such as infection,meningitis,arachnoiditis,and delayed wound healing.An ideal skull base reconstruction material should not only serve as a leak-proof barrier but also pro-mote skull base bone regeneration.To fulfill this challenge,this research designed and fabricated a Janus orthogonal bilayer nanofiber membrane(OPCL/PG-PCPP).The aligned PCL(APCL)nanofibers were con-stituted as the top layer to resist cerebrospinal fluid leakage,while the perpendicular PCL/gelatin(APG)fibers with calcium polyphosphate encapsulated polydopamine nanoparticles(CPP@PDA,labeled as PCPP)were designed as the bottom layer(APG-PCPP)to facilitate osteoblast migration and osteogenic differen-tiation.Among these,APG-1%PCPP nanofibers demonstrated the most effective induction of osteogenic differentiation in bone marrow mesenchymal stem cells(rBMSCs).Subsequent in vivo animal experi-ments revealed that the bone surface area(BS),bone volume fraction(BV/TV),and number of trabec-ulae(Tb.N)in the APG-1%PCPP group were twice as high as those in the control group,which confirmed the good osteogenic potentials.Therefore,due to its unique leak-proof and osteoinductive properties,the OPCL/PG-PCPP membrane holds promise as an applicable skull base reconstruction material in the field of neurosurgery.展开更多
Escherichia coli(E.coli)and Staphylococcus aureus(S.aureus)are the most typical pathogenic bacteria with a significantly high risk of bio-contamination,widely existing in hospital and public places.Recent studies on a...Escherichia coli(E.coli)and Staphylococcus aureus(S.aureus)are the most typical pathogenic bacteria with a significantly high risk of bio-contamination,widely existing in hospital and public places.Recent studies on antibacterial materials and the related mechanisms have attracted more interests of researchers.However,the antibacterial behavior of materials is usually evaluated separately on the single bacterial strain,which is far from the practical condition.Actually,the interaction between the polymicrobial communities can promote the growing profile of bacteria,which may weaken the antibacterial effect of materials.In this work,a 420 copper-bearing martensitic stainless steel(420 CuSS)was studied with respect to its antibacterial activity and the underlying mechanism in a co-culturing infection model using both E.coli and S.au reus.Observed via plating and counting colony forming units(CFU),Cu releasing,and material characterization,420 CuSS was proved to present excellent antibacterial performance against the mixed bacteria with an approximately 99.4%of antibacterial rate.In addition,420 CuSS could effectively inhibit the biofilm formation on its surfaces,resulting from a synergistic antibacterial effect of Cu ions,Fe ions,reactive oxygen species(ROS),and proton consumption of bacteria.展开更多
Bone tissue engineering(BTE)has proven to be a promising strategy for bone defect repair.Due to its excellent biological properties,gelatin methacrylate(GelMA)hydrogels have been used as bioinks for 3D bioprinting in ...Bone tissue engineering(BTE)has proven to be a promising strategy for bone defect repair.Due to its excellent biological properties,gelatin methacrylate(GelMA)hydrogels have been used as bioinks for 3D bioprinting in some BTE studies to produce scaffolds for bone regeneration.However,applications for load-bearing defects are limited by poor mechanical properties and a lack of bioactivity.In this study,3D printing technology was used to create nano-attapulgite(nano-ATP)/GelMA composite hydrogels loaded into mouse bone mesenchymal stem cells(BMSCs)and mouse umbilical vein endothelial cells(MUVECs).The bioprintability,physicochemical properties,and mechanical properties were all thoroughly evaluated.Our findings showed that nano-ATP groups outperform the control group in terms of printability,indicating that nano-ATP is beneficial for printability.Additionally,after incorporation with nano-ATP,the mechanical strength of the composite hydrogels was significantly improved,resulting in adequate mechanical properties for bone regeneration.The presence of nano-ATP in the scaffolds has also been stud-ied for cell-material interactions.The findings show that cells within the scaffold not only have high viability but also a clear proclivity to promote osteogenic differentiation of BMSCs.Besides,the MUVECs-loaded composite hydrogels demonstrated increased angiogenic activity.A cranial defect model was also developed to evaluate the bone repair capability of scaffolds loaded with rat BMSCs.According to histo-logical analysis,cell-laden nano-ATP composite hydrogels can effectively im prove bone regeneration and promote angiogenesis.This study demonstrated the potential of nano-ATP for bone tissue engineering,which should also increase the clinical practicality of nano-ATP.展开更多
Hydrogels with tissue adhesiveness have demonstrated great promise for wearable electronics,artificial skin,soft robotics,and tissue repair.Nevertheless,adhesive hydrogels that are capable of sealing and hemostasis of...Hydrogels with tissue adhesiveness have demonstrated great promise for wearable electronics,artificial skin,soft robotics,and tissue repair.Nevertheless,adhesive hydrogels that are capable of sealing and hemostasis of wound with severe hemorrhage still lack.For this purpose,a series of ionically crosslinked starch hydrogels were developed here.The viscoelastic properties and tissue adhesiveness of the starch hydrogels were investigated.It is shown that the starch and cross linkers had significant influence on the viscoelastic properties of the starch hydrogels,which further resulted in varied tissue adhesiveness.Among the starch gels,there was one exhibiting a unique and stable"Gel Point"viscoelastic characteristic and it was named as gel-point adhesive hydrogel(GPAH).GPAH showed electrical conductivity,high tissue adhesiveness,high stretch-ability,self-healing capability,injectability,and degradability.The GPAH also exhibited high cytocompatibility,low hemolysis risk,and strong antibacterial effect.The wound sealing and hemostatic performance of GPAH was further evaluated by a rat femoral artery injury model.The blood loss after the sealing of GPAH(2.4±1.3 g)was significantly decreased compared to the group using gauze for sealing(6.3±1.5 g).Meanwhile,GPAH did not cause pathological changes of the soft tissues surrounding the wound.The above results indicate that GPAH,with high tissue adhesiveness,suitable viscoelastic property,strong antibacterial capacity,as well as electro-conductivity,bears great potential for the applications in smart wound management.展开更多
It has always been a dream to construct tissues and even organs for transplantation to replace those with defects caused by diseases or injuries.Tissue engineering is another milestone in the developmental history of ...It has always been a dream to construct tissues and even organs for transplantation to replace those with defects caused by diseases or injuries.Tissue engineering is another milestone in the developmental history of life science after cellular and molecular bioscience.Nevertheless,despite decades of rapid de-velopment,tissue-engineered biomaterials have not been widely used clinically.Biomaterials constructed by physical and chemical methods have lots of difficulty in precisely mimicking the macroscopic and mi-croscopic structures of human tissues.The ultimate way to build organoid tissue for regeneration is to enable the cells to take the initiative and build suitable functions.Based on the thoughts of tissue engi-neering,organoid technology holds great potential as a research tool for a wide range of fields,including developmental biology,disease pathology,cell biology,precision medicine,and drug toxicity and efficacy testing.This technology also holds tremendous potential for regenerative medicine,as organoids present the possibility for autologous and allogeneic cell therapy through the replacement of damaged or dis-eased tissues with organoid-propagated tissue or stem cell populations.In this review work,we briefly outlook the development history of organoid technology,summarize the current bottlenecks and the un-derlying reasons,and propose the unified term“function-oriented design in tissue engineering”,a new topic that may provide a solution to overcome these bottlenecks.展开更多
Mechanical stimuli are known to play critical roles in mediating tissue repair and regeneration. Recently, thisknowledge has led to a paradigm shift toward proactive programming of biological functionalities of biomat...Mechanical stimuli are known to play critical roles in mediating tissue repair and regeneration. Recently, thisknowledge has led to a paradigm shift toward proactive programming of biological functionalities of biomaterialsby leveraging mechanics–geometry–biofunction relationships, which are beginning to shape the newly emergingfield of mechanobiomaterials. To profile this emerging field, this article aims to elucidate the fundamentalprinciples in modulating biological responses with material–tissue mechanical interactions, illustrate recentfindings on the relationships between material properties and biological responses, discuss the importance ofmathematical/physical models and numerical simulations in optimizing material properties and geometry, andoutline design strategies for mechanobiomaterials and their potential for tissue repair and regeneration. Giventhat the field of mechanobiomaterials is still in its infancy, this article also discusses open questions and challengesthat need to be addressed.展开更多
Healing of chronic diabetic wounds is challenging due to complications of severe inflammatory microenvironment,bacterial infection and poor vascular formation.Herein,a novel injectable polyvinyl alcohol-hyaluronic aci...Healing of chronic diabetic wounds is challenging due to complications of severe inflammatory microenvironment,bacterial infection and poor vascular formation.Herein,a novel injectable polyvinyl alcohol-hyaluronic acid-based composite hydrogel was developed,with tannic acid(TA)and silicate functionalization to fabricate an‘all-in-one’hydrogel PTKH.On one hand,after being locally injected into the wound site,the hydrogel underwent a gradual sol-gel transition in situ,forming an adhesive and protective dressing for the wound.Manipulations of rheological characteristics,mechanical properties and swelling ability of PTKH could be performed via regulating TA and silicate content in hydrogel.On the other hand,PTKH was capable of eliminating reactive oxygen species overexpression,combating infection and generating a cell-favored microenvironment for wound healing acceleration in vitro.Subsequent animal studies demonstrated that PTKH could greatly stimulate angiogenesis and epithelization,accompanied with inflammation and infection risk reduction.Therefore,in consideration of its impressive in vitro and in vivo outcomes,this‘all-in-one’multifunctional hydrogel may hold promise for chronic diabetic wound treatment.展开更多
The bone fracture cases have been increasing yearly,accompanied by the increased number of patients experiencing non-union or delayed union after their bone fracture.Although clinical materials facilitate fracture hea...The bone fracture cases have been increasing yearly,accompanied by the increased number of patients experiencing non-union or delayed union after their bone fracture.Although clinical materials facilitate fracture healing(e.g.,metallic and composite materials),they cannot fulfill the requirements due to the slow degradation rate,limited osteogenic activity,inadequate osseointegration ability,and suboptimal mechanical properties.Since early 2000,nanomaterials successfully mimic the nanoscale features of bones and offer unique properties,receiving extensive attention.This paper reviews the achievements of nanomaterials in treating bone fracture(e.g.,the intrinsic properties of nanomaterials,nanomaterials for bone defect filling,and nanoscale drug delivery systems in treating fracture delayed union).Furthermore,we discuss the perspectives on the challenges and future directions of developing nanomaterials to accelerate fracture healing.展开更多
When biomaterials are implanted in the human body,the surfaces of the implants become favorable sites for microbial adhesion and biofilm formation,causing peri-implant infection which frequently results in the failure...When biomaterials are implanted in the human body,the surfaces of the implants become favorable sites for microbial adhesion and biofilm formation,causing peri-implant infection which frequently results in the failure of prosthetics and revision surgery.Ti-Mo alloy is one of the commonly used implant materials for load-bearing bone replacement,and the prevention of infection of Ti-Mo implants is therefore crucial.In this study,bacterial inhibitory copper(Cu)was added to Ti-Mo matrix to develop a novel Ti-Mo-Cu alloy with bacterial inhibitory property.The effects of Cu content on microstructure,tensile properties,cytocompatibility,and bacterial inhibitory ability of Ti-Mo-Cu alloy were systematically investigated.Results revealed that Ti-10Mo-1Cu alloy consisted ofαandβphases,while there were a few Ti2Cu intermetallic compounds existed for Ti-10Mo-3Cu and Ti-10Mo-5Cu alloys,in addition toαandβphases.The tensile strength of Ti-10Mo-xCu alloy increased with Cu content while elongation decreased.Ti-10Mo-3Cu alloy exhibited an optimal tensile strength of 1098.1 MPa and elongation of 5.2%.Cytocompatibility study indicated that none of the Ti-10Mo-xCu alloys had a negative effect on MC3T3-E1 cell proliferation.Bacterial inhibitory rates against S.aureus and E.coli increased with the increase in Cu content of Ti-10Mo-xCu alloy,within the ranges of 20-60%and 15-50%,respectively.Taken together,this study suggests that Ti-10Mo-3Cu alloy with high strength,acceptable elongation,excellent cytocompatibility,and the bacterial inhibitory property is a promising candidate for biomedical implant applications.展开更多
Background:Magnesium ions play crucial roles in maintaining cellular functions.Research has shown that Mg^(2+)can promote angiogenesis,indicating its potential for treating cardiovascular ischemic diseases.However,con...Background:Magnesium ions play crucial roles in maintaining cellular functions.Research has shown that Mg^(2+)can promote angiogenesis,indicating its potential for treating cardiovascular ischemic diseases.However,conventional intravenous or oral administration of Mg^(2+)presents several challenges,including the risk of systemic side effects,diminished bioavailability,and a lack of targeted delivery mechanisms.In this study,we designed an Mg^(2+)-releasing adhesive tissue patch(MgAP)that enables the dural release of Mg^(2+)ions.Methods:A novel MgAP was developed on the basis of ionic crosslinking.Fourier transform infrared spectroscopy confirmed the chemical structure,whereas rheological analysis demonstrated stable mechanical properties and adaptability to dynamic loads.Sustained Mg^(2+)release was quantified over 7 days by inductively coupled plasma-mass spectrometry.In a rat acute myocardial infarction model,we performed echocardiography and strain analysis to assess cardiac function and histological staining to evaluate adverse remodeling.We also verified the proangiogenic effect through in vitro tube formation and in vivo immunofluorescence assays.Furthermore,transcriptomics and Western blotting were performed to explore the underlying mechanism.Additional assessments were also carried out in a rat model of lower limb ischemia.Results:Compared with intravenous administration of magnesium chloride,MgAP application effectively improved cardiac function and reduced adverse remodeling in the myocardial infarction rat model.The left ventricular ejection fraction increased by 20.3±6.6%,and the cardiac radial strain improved by 27.4±4.1%.The cardiac fibrosis area and cell apoptosis rate decreased by 10.9±1.2% and 32.1±5.5%,respectively.RNA sequencing analysis also highlighted the upregulation of genes related to cardiac electrophysiological properties,structural and functional intercellular connections,and revascularization.The increased gap junction protein expression and restored local blood supply could contribute to the cardiac repair process posttreatment.The proangiogenic effect of MgAP was also observed in the rat limb ischemia model.Conclusions:The above results revealed the convincing vascular regeneration effect of an ion therapy-based hydrogel,which enabled the local delivery of Mg^(2+)to the targeted ischemic tissue,aiding in cardiac and lower limb repair.This study presents a novel strategy and highlights its potential for use across various ischemic conditions.展开更多
Severe skin wounds cause great problems and sufferings to patients.In this study,an injectable wound dressing based on strontium ion cross-linked starch hydrogel(SSH)was developed and evaluated.The good inject-ability...Severe skin wounds cause great problems and sufferings to patients.In this study,an injectable wound dressing based on strontium ion cross-linked starch hydrogel(SSH)was developed and evaluated.The good inject-ability of SSH made it easy to be delivered onto the wound surface.The good tissue adhesiveness of SSH ensured a firm protection of the wound.Besides,SSH supported the proliferation of NIH/3T3 fibroblasts and facilitated the migration of human umbilical vein endothelial cells(HUVECs).Importantly,SSH exhibited strong antibacterial effects on Staphylococcus aiireiis(S.ai/rec/s),which could prevent wound infection.These results demonstrate that SSH is a promising wound dressing material for promoting wound healing.展开更多
基金supported by the National Natural Science Foundation of China(No.U21A2055),Natural Science Foundation of Tianjin of China(No.21JCQNJC01280)Tianjin Key R&D Program Beijing-Tianjin-Hebei Collaborative Innovation Project(No.22YFXTHZ00120).
文摘The poor surface conditions and osseointegration capacity of 3D printed Ti6Al4V implants(3DPT)significantly influence their performance as orthopedic and dental implants.In this work,we creatively introduce a one-step femtosecond laser treatment to improve the surface conditions and osteointegration.The surface characterization,mechanical properties,corrosion resistance,and biological responses were investigated.These results found that femtosecond laser eliminated defects like embedded powders and superficial cracks while forming the nano cones-like structures surface on 3DPT,leading to enhanced osseointegration,anti-corrosion,and anti-fatigue performance.Molecular dynamics simulations revealed the ablation removal mechanism and the formation of nano cone-like structures.These findings were further supported by the in vivo studies,showing that the FS-treated implants had superior bone-implant contact and osseointegration.Hence,the one-step femtosecond laser method is regarded as a promising surface modification method for improving the functional performance of Ti-based orthopedic implants.
基金supported by the National Natu-ral Science Foundation of China(Nos.82025025,32171321,and 81622032)the National Key Research and Development Program of China(No.2020YFC1107401)+4 种基金the Suzhou Science and Tech-nology Project(No.SYS2019022)the China Postdoctoral Science Foundation(No.2020T130459)the Full-time Talents Program of Hebei Province of China(No.2020HBQZYC012)the Priority Aca-demic Program Development of Jiangsu High Education Institu-tions(PAPD),Expert Workstation of Yunnan Province of China(202205AF150025)Innovation Fund of National Clinical Re-search Center for Orthopedics,Sports Medicine and Rehabilitation of China(No.2021-NCRC-CXJJ-ZH-17).
文摘Although hydrogels have demonstrated great potential as new wound dressing materials,their instability in shape and/or mechanical characteristics due to water loss or freezing remains a shortcoming for wound care application.Herein,a novel injectable organohydrogel(IOH)of physically crosslinked polyvinyl alco-hol/glycerol that possesses non-drying capability and high stability at low temperature was developed for wound care.IOH has a skin-like stiffness(G’,∼280 Pa),high injectability,self-healing capability,high water-vapor transmission rate,and bacterial inhibitory effect.IOH exhibits high shape and mechanical stabilities after curing at 37°C and 50%relative humidity for 7 days or after curing at-20°C for 1 day.In addition,glycerol in IOH enabled an efficient loading and release of water-insoluble curcumin,a well-known anti-bacterial and anti-inflammation drug.The curcumin-releasing IOH(Cur-IOH)demonstrated significantly enhanced anti-bacterial performance compared to IOH or curcumin-loading polyvinyl alco-hol hydrogel.More importantly,Cur-IOH could accelerate wound healing in a murine full-thickness skin defect wound model,revealing improved wound contraction,collagen deposition,angiogenesis,and epi-dermis formation.This study demonstrates the great potential of organohydrogel for the reparation of severe wounds and Cur-IOH as a new type of injectable wound healing material.
基金sponsored by the National Natural Science Foundation of China(Nos.81622032,31801585,81930070and 51672184)Suzhou Science and Technology Project(No.SYS2019022)+3 种基金Natural Science Foundation of Jiangsu Province(Nos.BK20180837 and BK20181045)Postdoctoral Science Foundation(No.2018T110546)Natural Science Research of Jiangsu Higher Education Institutions(No.17KJA180011)the Priority Aca-demic Program Development of Jiangsu High Education Institutions(PAPD)。
文摘There is a lack of effective tissue repair and regeneration strategies in current clinical practices.Numerous studies have suggested that smart or responsive biomaterials possessing the ability to respond to endogenous stimuli in vivo may positively mediate the tissue micro-environment towards a tissue repair or regeneration.Mechanical stimuli,which constantly exist in a wide range of biological systems and are involved in almost all the physiological processes,belong to such stimuli to which responsive biomaterials can respond.In recent studies,a new type of smart biomaterials,which can dynamically adapt to the mechanical stimuli in vivo and thus has specific functionality consistently mediated by such mechanical stimuli,has emerged.In contrast to common biomaterials that passively react to the mechanical environment of an implantation site,such mechano-active biomaterials have enabled various active or automatic strategies for tissue repair or regeneration,such as providing precise spatial-temporal controls on delivery of drugs or cells in the organs of the musculoskeletal and the circulatory systems;in situ reconstructing the original or a favorable mechanical environment at a lesion site;and accelerating the tissue remodeling or healing process via a mechanobiological effect.This article elucidates a perspective of perfecting tissue repair or regeneration using mechano-active biomaterials,especially highlighting the rationale behind the concept of mechano-active biomaterials and their potential in the repair or regeneration of musculoskeletal and cardiovascular tissues.Albeit outstanding challenges and unknowns,the emergence of mechano-active biomaterials has become a new avenue for tissue engineering and regenerative medicine.
基金financially supported by SFB 765 and the Focus Area Nanoscale of Freie Universitat Berlinfinancial support from China Scholarship Councilsupported by the DFG and Dr. Pamela Winchester (Freie Universitat Berlin, Germany) for language polishing。
文摘Bacterial infection and osteogenic integration are the two main problems that cause severe complications after surgeries. In this study, the antibacterial and osteogenic properties were simultaneously introduced in biomaterials, where copper nanoparticles(Cu NPs) were generated by in situ reductions of Cu ions into a mussel-inspired hyperbranched polyglycerol(MI-h PG) coating via a simple dip-coating method.This hyperbranched polyglycerol with 10 % catechol groups’ modification presents excellent antifouling property, which could effectively reduce bacteria adhesion on the surface. In this work, polycaprolactone(PCL) electrospun fiber membrane was selected as the substrate, which is commonly used in biomedical implants in bone regeneration and cardiovascular stents because of its good biocompatibility and easy post-modification. The as-fabricated Cu NPs-incorporated PCL membrane [PCL-(MI-h PG)-Cu NPs]was confirmed with effective antibacterial performance via in vitro antibacterial tests against Staphylococcus aureus(S. aureus), Escherichia coli(E. coli), and multi-resistant E. coli. In addition, the in vitro results demonstrated that osteogenic property of PCL-(MI-h PG)-Cu NPs was realized by upregulating the osteoblast-related gene expressions and protein activity. This study shows that antibacterial and osteogenic properties can be balanced in a surface coating by introducing Cu NPs.
基金financial support from the National Natural Science Foundation of China(Nos.82025025,51672184,31801585,81622032,32171321)National Key Research and Development Program of China(No.2020YFC1107401)+2 种基金Suzhou Science and Technology Project(No.SYS2019022)China Postdoctoral Science Foundation(No.2020T130459)the Priority Academic Program Development of Jiangsu High Education Institutions(PAPD)。
文摘Repair of severe skin tissue injury remains a great challenge and wound infection is still a formidable problem.In this study,new macroporous and antibacterial gelatin/alginate(SAG)-based hydrogels for wound repair were designed and developed based on in-situ gas foaming method and ion release strategy as a result of Mg-Cu particles degradation in the hydrogel matrix.The addition of Mg-Cu particles decreased the storage modulus of SAG,maintained its mechanical resilience and enhanced its water-absorbing capability.Moreover,the water vapor transmission rate of SAG added with 2 wt.%Mg-Cu(SAG-2 MC)was 124%of that of medical gauze and 804%of commercial Tegaderm^(TM)film dressing.The bacterial inhibition rates of SAG-2 MC against S.aureus.E.coli and P.aeruginosa reached 99.9%±0.1%,98.7%±1.2%and 98.0%±0.7%,respectively,significantly greater than those of the SAG hydrogel and Mg particle-modified hydrogels.In addition,SAG-2 MC hydrogel was biocompatible and promoted cell migration.In vivo experiment results indicated that SAG-2 MC significantly accelerated the skin wound healing in murine model as demonstrated by higher epidermis thickness,more collagen deposition and enhanced angiogenesis compared with SAG-OMC,SAG-2 M and TegadermTM film.In summary,Mg-Cu particles have great potential to modulate the physiochemical and biological properties of SAG hydrogels.Mg-Cu particle-modified SAG hydrogels reveal significant promise in the treatment of severe skin wound or other soft tissue lesions.
基金financially supported by the Sichuan Science and Technology Program(No.2021YFS0020)the Natural Science Foundation of China(No.32001002)supported by the second batch(“3.1 Investigating technologies of assessing the safety and effectiveness of nano-medical device products”,“5.3 Investigating innovative supervision and assessment technologies of tissue engineered medical device products”,“5.4 Research,development and translation of innovative biomaterials”and“5.5 Research on technical evaluation of recombinant collagens,cartilagerepair materials and antimicrobial orthopedic/dental materials”)of Chinese Drug Regulatory Science Action Plan of National Medical Products Administration。
文摘The fast development of both biomaterials and regulatory science calls for a convergence,which is addressed in this article via their link through medical products of biomaterials and related safety and efficacy evaluation.The updated definition of biomaterials,and concepts of biomaterials-related medical products and so-called medical-grade and implantable materials are firstly introduced.Then a brief overview of the concept and history of regulatory science and its assessment of safety and efficacy of medical products,as well as the currently ongoing biomaterials-related regulatory science programs are presented.Finally,the opportunities provided by regulatory science for biomaterials as well as challenges on how to develop a biomaterials-based regulatory science system are discussed.As the first article in the field to elucidate the relationship between biomaterials and regulatory science,key take-home messages include(1)biomaterials alone are not medical products;(2)regulatory authorities approve/clear final medical products,not biomaterials;(3)there is no definition/regulation on the so-called medical-grade or implantable materials;and(4)safety and efficacy refer to final medical products,not biomaterials alone.
基金financially supported by the National Natural Science Foundation of China(No.82102908)the Natural Science Foundation of Tianjin of China(No.22JCQNJC01260)+3 种基金Natural Science Foundation of Hebei Province of China(No.H2024202004)National Natural Science Foundation of China(No.U23A6008)National Key Research and Development Program of China(No.2023YFC2412300)Natural Science Foundation of Hebei Province of China(No.H2022202007)。
文摘Despite the considerable potentiality of photodynamic therapy(PDT)in cancer treatment,conventional hydrophobic photosensitizers cause obstacles for in vivo application,while their inert structures are difficult to chemically modify.Additionally,undesirable tumor hypoxia resulting from oxygen consumption also discounts the therapeutic efficacy of PDT.Herein,we developed a self-strengthened nanogel with reactive oxygen species(ROS)trigger-explosive property.IR780 was spontaneous assembled within the conical cavity of cyclodextrin(β-CD)using host-vip interactions,while adjacent IR780 molecules on the dextrin backbone with hydrophobic interaction andπconjugation induced nanogel formation.Simultaneously,hydrophilic compound tirapazamine(TPZ)was incorporated into nanogel for synergistic tumor treatment.The inherent high levels of ROS in tumor can break down boronic ester bond linker of nanogel,initiating its disintegration.Furthermore,our findings indicate the ROS level(including H2O2and1O2)can be transiently enhanced during PDT process at the animal level,which accelerates the explosion of nanogel.Notably,the IR780@β-CD module exhibited enhanced ROS generation efficiency during PDT with the continues explosion of nanogel,which further strengthens nanogel disintegration,tumor phototherapy and cargo releasement.Additionally,the released TPZ is activated under hypoxic conditions after PDT treatment,addressing the limitations of PDT and facilitating multi-synergistic tumor treatment.
基金supported by the National Key Research and Development Program of China(No.2023YFC2412300)the National Natural Science Foundation of China(Nos.82025025,U23A6008,U22A20162,and U21A2055)+3 种基金the Natural Science Foun-dation of Hebei Province of China(No.H2022202007)the Full-time Talents Program of Hebei Province of China(No.2020HBQZYC012)the Natural Science Foundation of Tianjin of China(Nos.21JCYBJC01380 and 21JCZDJC01110)the Scientific Research Project of Tianjin Education Commission(No.2022KJ096).
文摘In neurosurgery procedures,cerebrospinal fluid leakage is a commonly encountered complication.Re-constructing skull base defects with patch materials can reduce the risk of cerebrospinal fluid leakage which can lead to serious issues such as infection,meningitis,arachnoiditis,and delayed wound healing.An ideal skull base reconstruction material should not only serve as a leak-proof barrier but also pro-mote skull base bone regeneration.To fulfill this challenge,this research designed and fabricated a Janus orthogonal bilayer nanofiber membrane(OPCL/PG-PCPP).The aligned PCL(APCL)nanofibers were con-stituted as the top layer to resist cerebrospinal fluid leakage,while the perpendicular PCL/gelatin(APG)fibers with calcium polyphosphate encapsulated polydopamine nanoparticles(CPP@PDA,labeled as PCPP)were designed as the bottom layer(APG-PCPP)to facilitate osteoblast migration and osteogenic differen-tiation.Among these,APG-1%PCPP nanofibers demonstrated the most effective induction of osteogenic differentiation in bone marrow mesenchymal stem cells(rBMSCs).Subsequent in vivo animal experi-ments revealed that the bone surface area(BS),bone volume fraction(BV/TV),and number of trabec-ulae(Tb.N)in the APG-1%PCPP group were twice as high as those in the control group,which confirmed the good osteogenic potentials.Therefore,due to its unique leak-proof and osteoinductive properties,the OPCL/PG-PCPP membrane holds promise as an applicable skull base reconstruction material in the field of neurosurgery.
基金financially supported by the National Natural Science Foundation of China(Nos.51101154,51631009,51672184,and 51371168)the National Basic Research Program of China(No.2012CB619101)National Key R&D Program of China(No.2020YFC1107400)。
文摘Escherichia coli(E.coli)and Staphylococcus aureus(S.aureus)are the most typical pathogenic bacteria with a significantly high risk of bio-contamination,widely existing in hospital and public places.Recent studies on antibacterial materials and the related mechanisms have attracted more interests of researchers.However,the antibacterial behavior of materials is usually evaluated separately on the single bacterial strain,which is far from the practical condition.Actually,the interaction between the polymicrobial communities can promote the growing profile of bacteria,which may weaken the antibacterial effect of materials.In this work,a 420 copper-bearing martensitic stainless steel(420 CuSS)was studied with respect to its antibacterial activity and the underlying mechanism in a co-culturing infection model using both E.coli and S.au reus.Observed via plating and counting colony forming units(CFU),Cu releasing,and material characterization,420 CuSS was proved to present excellent antibacterial performance against the mixed bacteria with an approximately 99.4%of antibacterial rate.In addition,420 CuSS could effectively inhibit the biofilm formation on its surfaces,resulting from a synergistic antibacterial effect of Cu ions,Fe ions,reactive oxygen species(ROS),and proton consumption of bacteria.
基金This research was funded by Jiangsu Province’s Key Project of Science and Technology(Grant No.BE2018644)Changzhou Health Commission’s Young Talents Science and Technology project(Grant No.QN202029).
文摘Bone tissue engineering(BTE)has proven to be a promising strategy for bone defect repair.Due to its excellent biological properties,gelatin methacrylate(GelMA)hydrogels have been used as bioinks for 3D bioprinting in some BTE studies to produce scaffolds for bone regeneration.However,applications for load-bearing defects are limited by poor mechanical properties and a lack of bioactivity.In this study,3D printing technology was used to create nano-attapulgite(nano-ATP)/GelMA composite hydrogels loaded into mouse bone mesenchymal stem cells(BMSCs)and mouse umbilical vein endothelial cells(MUVECs).The bioprintability,physicochemical properties,and mechanical properties were all thoroughly evaluated.Our findings showed that nano-ATP groups outperform the control group in terms of printability,indicating that nano-ATP is beneficial for printability.Additionally,after incorporation with nano-ATP,the mechanical strength of the composite hydrogels was significantly improved,resulting in adequate mechanical properties for bone regeneration.The presence of nano-ATP in the scaffolds has also been stud-ied for cell-material interactions.The findings show that cells within the scaffold not only have high viability but also a clear proclivity to promote osteogenic differentiation of BMSCs.Besides,the MUVECs-loaded composite hydrogels demonstrated increased angiogenic activity.A cranial defect model was also developed to evaluate the bone repair capability of scaffolds loaded with rat BMSCs.According to histo-logical analysis,cell-laden nano-ATP composite hydrogels can effectively im prove bone regeneration and promote angiogenesis.This study demonstrated the potential of nano-ATP for bone tissue engineering,which should also increase the clinical practicality of nano-ATP.
基金sponsored by the National Natural Science Foundation of China(No.81622032 and 51672184)Suzhou Science and Technology Project(No.SYS2019022)+2 种基金Natural Science Research of Jiangsu Higher Education Institutions(No.17KJA180011)Natural Science Foundation of Jiangsu Province(No.BK20181045)Jiangsu Innovation and Entrepreneurship Program and the Priority Academic Program Development of Jiangsu High Education Institutions(PAPD)。
文摘Hydrogels with tissue adhesiveness have demonstrated great promise for wearable electronics,artificial skin,soft robotics,and tissue repair.Nevertheless,adhesive hydrogels that are capable of sealing and hemostasis of wound with severe hemorrhage still lack.For this purpose,a series of ionically crosslinked starch hydrogels were developed here.The viscoelastic properties and tissue adhesiveness of the starch hydrogels were investigated.It is shown that the starch and cross linkers had significant influence on the viscoelastic properties of the starch hydrogels,which further resulted in varied tissue adhesiveness.Among the starch gels,there was one exhibiting a unique and stable"Gel Point"viscoelastic characteristic and it was named as gel-point adhesive hydrogel(GPAH).GPAH showed electrical conductivity,high tissue adhesiveness,high stretch-ability,self-healing capability,injectability,and degradability.The GPAH also exhibited high cytocompatibility,low hemolysis risk,and strong antibacterial effect.The wound sealing and hemostatic performance of GPAH was further evaluated by a rat femoral artery injury model.The blood loss after the sealing of GPAH(2.4±1.3 g)was significantly decreased compared to the group using gauze for sealing(6.3±1.5 g).Meanwhile,GPAH did not cause pathological changes of the soft tissues surrounding the wound.The above results indicate that GPAH,with high tissue adhesiveness,suitable viscoelastic property,strong antibacterial capacity,as well as electro-conductivity,bears great potential for the applications in smart wound management.
基金This work was financially supported by the National Natural Science Foundation of China(Nos.U22A20162,31900583,32071351,81772400,82102604,and 81960395)the Natural Science Foundation of Guangzhou City(No.201807010031)+5 种基金the Foundation of Shenzhen Committee for Science and Technology Innovation(Nos.JCYJ20190809142211354,and GJHZ20180929160004704)the Sanming Project of Medicine in Shenzhen(No.SZSM201911002)the Beijing Municipal Health Commission(Nos.BMHC-2021-6,BMHC-2019-9,BMHC-2018-4,and PXM2020_026275_000002)the AOCMF Translational approaches for bone constructs(No.AOCMF-21-04S)the Sun Yatsen University Clinical Research 5010 Program(No.2019009)the Academic Affairs Office of Sun Yat-sen University(Nos.202211583,and 202211589).
文摘It has always been a dream to construct tissues and even organs for transplantation to replace those with defects caused by diseases or injuries.Tissue engineering is another milestone in the developmental history of life science after cellular and molecular bioscience.Nevertheless,despite decades of rapid de-velopment,tissue-engineered biomaterials have not been widely used clinically.Biomaterials constructed by physical and chemical methods have lots of difficulty in precisely mimicking the macroscopic and mi-croscopic structures of human tissues.The ultimate way to build organoid tissue for regeneration is to enable the cells to take the initiative and build suitable functions.Based on the thoughts of tissue engi-neering,organoid technology holds great potential as a research tool for a wide range of fields,including developmental biology,disease pathology,cell biology,precision medicine,and drug toxicity and efficacy testing.This technology also holds tremendous potential for regenerative medicine,as organoids present the possibility for autologous and allogeneic cell therapy through the replacement of damaged or dis-eased tissues with organoid-propagated tissue or stem cell populations.In this review work,we briefly outlook the development history of organoid technology,summarize the current bottlenecks and the un-derlying reasons,and propose the unified term“function-oriented design in tissue engineering”,a new topic that may provide a solution to overcome these bottlenecks.
基金supported by the National Natural Science Foundation of China(grant numbers 82025025,U23A6008,32171321,32371385,81802155,51672184 and 81622032)National Key Research and Development Project of China(grant number 2023YFC2412300)+7 种基金Natural Science Foundation of Hebei Province of China(grant number H2022202007)Full-time Talents Program of Hebei Province of China(grant number 2020HBQZYC012)Natural Science Foundation of Tianjin of China(grant number 21JCZDJC01110,21JCYBJC01030)Academician Expert Workstation of Yunnan Province of China(202205AF150025)Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)Key Laboratory of Orthopaedics of Suzhou(SZS2022017)Scientific Research Project of Tianjin Education Commission(2022KJ096)Science and Technology Innovation Project of Foshan City(1920001000025).
文摘Mechanical stimuli are known to play critical roles in mediating tissue repair and regeneration. Recently, thisknowledge has led to a paradigm shift toward proactive programming of biological functionalities of biomaterialsby leveraging mechanics–geometry–biofunction relationships, which are beginning to shape the newly emergingfield of mechanobiomaterials. To profile this emerging field, this article aims to elucidate the fundamentalprinciples in modulating biological responses with material–tissue mechanical interactions, illustrate recentfindings on the relationships between material properties and biological responses, discuss the importance ofmathematical/physical models and numerical simulations in optimizing material properties and geometry, andoutline design strategies for mechanobiomaterials and their potential for tissue repair and regeneration. Giventhat the field of mechanobiomaterials is still in its infancy, this article also discusses open questions and challengesthat need to be addressed.
基金supported by the National Natural Science Foundation of China(82025025)Natural Science Foundation of Hebei Province of China(H2022202007)+3 种基金Full-time Talents Program of Hebei Province of China(2020HBQZYC012)Natural Science Foundation of Tianjin of China(21JCYBJC01030,21JCZDJC01110)The Scientific Research Project of Tianjin Education Commission(2022KJ096)Academician Expert Workstation of Yunnan Province of China(202205AF150025).
文摘Healing of chronic diabetic wounds is challenging due to complications of severe inflammatory microenvironment,bacterial infection and poor vascular formation.Herein,a novel injectable polyvinyl alcohol-hyaluronic acid-based composite hydrogel was developed,with tannic acid(TA)and silicate functionalization to fabricate an‘all-in-one’hydrogel PTKH.On one hand,after being locally injected into the wound site,the hydrogel underwent a gradual sol-gel transition in situ,forming an adhesive and protective dressing for the wound.Manipulations of rheological characteristics,mechanical properties and swelling ability of PTKH could be performed via regulating TA and silicate content in hydrogel.On the other hand,PTKH was capable of eliminating reactive oxygen species overexpression,combating infection and generating a cell-favored microenvironment for wound healing acceleration in vitro.Subsequent animal studies demonstrated that PTKH could greatly stimulate angiogenesis and epithelization,accompanied with inflammation and infection risk reduction.Therefore,in consideration of its impressive in vitro and in vivo outcomes,this‘all-in-one’multifunctional hydrogel may hold promise for chronic diabetic wound treatment.
基金the financial support from the Postdoctoral Fund of Hebei Medical University,Key Supported Projects of the Joint Fund of the National Natural Science Foundation of China(Grant No.U22A20357)National Key R&D Program of China(Grant No.2020YFC1107601)+1 种基金Chunyu Project Outstanding Youth Fund of Hebei Medical University(No.CYYQ2023004)the China Postdoctoral Science Foundation(No.2023M730914 and 2023TQ0103).
文摘The bone fracture cases have been increasing yearly,accompanied by the increased number of patients experiencing non-union or delayed union after their bone fracture.Although clinical materials facilitate fracture healing(e.g.,metallic and composite materials),they cannot fulfill the requirements due to the slow degradation rate,limited osteogenic activity,inadequate osseointegration ability,and suboptimal mechanical properties.Since early 2000,nanomaterials successfully mimic the nanoscale features of bones and offer unique properties,receiving extensive attention.This paper reviews the achievements of nanomaterials in treating bone fracture(e.g.,the intrinsic properties of nanomaterials,nanomaterials for bone defect filling,and nanoscale drug delivery systems in treating fracture delayed union).Furthermore,we discuss the perspectives on the challenges and future directions of developing nanomaterials to accelerate fracture healing.
基金supported by the National Natural Science Foundation of China(51922004,51874037,51672184)State Key Lab of Advanced Metals and Materials,University of Science and Technology Beijing(2019-Z14)+4 种基金Fundamental Research Funds for the Central Universities(FRF-TP-19005C1Z)the support from the European Commission via the H2020 MSCA RISE BAMOS programme(734156)Bo Su would like to thank financial support from the MRC(MR/S010343/1)the EU H2020 MSCA RISE Bio-TUNE programmethe support from the China Scholarship Council(CSC)for a CSC Ph.D.scholarship(201906460106).
文摘When biomaterials are implanted in the human body,the surfaces of the implants become favorable sites for microbial adhesion and biofilm formation,causing peri-implant infection which frequently results in the failure of prosthetics and revision surgery.Ti-Mo alloy is one of the commonly used implant materials for load-bearing bone replacement,and the prevention of infection of Ti-Mo implants is therefore crucial.In this study,bacterial inhibitory copper(Cu)was added to Ti-Mo matrix to develop a novel Ti-Mo-Cu alloy with bacterial inhibitory property.The effects of Cu content on microstructure,tensile properties,cytocompatibility,and bacterial inhibitory ability of Ti-Mo-Cu alloy were systematically investigated.Results revealed that Ti-10Mo-1Cu alloy consisted ofαandβphases,while there were a few Ti2Cu intermetallic compounds existed for Ti-10Mo-3Cu and Ti-10Mo-5Cu alloys,in addition toαandβphases.The tensile strength of Ti-10Mo-xCu alloy increased with Cu content while elongation decreased.Ti-10Mo-3Cu alloy exhibited an optimal tensile strength of 1098.1 MPa and elongation of 5.2%.Cytocompatibility study indicated that none of the Ti-10Mo-xCu alloys had a negative effect on MC3T3-E1 cell proliferation.Bacterial inhibitory rates against S.aureus and E.coli increased with the increase in Cu content of Ti-10Mo-xCu alloy,within the ranges of 20-60%and 15-50%,respectively.Taken together,this study suggests that Ti-10Mo-3Cu alloy with high strength,acceptable elongation,excellent cytocompatibility,and the bacterial inhibitory property is a promising candidate for biomedical implant applications.
基金supported by the National Natural Science Foundation of China(No.82161138023,82025025,32171321,32371385)Innovative research team of high-level local universities in Shanghai and a key laboratory program of the Education Commission of Shanghai Municipality(ZDSYS14005)+6 种基金Natural Science Foundation of Jiangsu Province(BK20240019)Natural Science Foundation of Hebei Province of China(grant number H2022202007)Full-time Talents Program of Hebei Province of China(grant number 2020HBQZYC012)Natural Science Foundation of Tianjin of China(grant number 21JCZDJC01110)Academician Expert Workstation of Yunnan Province of China(202205AF150025)Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)Key Laboratory of Orthopaedics of Suzhou(SZS2022017).
文摘Background:Magnesium ions play crucial roles in maintaining cellular functions.Research has shown that Mg^(2+)can promote angiogenesis,indicating its potential for treating cardiovascular ischemic diseases.However,conventional intravenous or oral administration of Mg^(2+)presents several challenges,including the risk of systemic side effects,diminished bioavailability,and a lack of targeted delivery mechanisms.In this study,we designed an Mg^(2+)-releasing adhesive tissue patch(MgAP)that enables the dural release of Mg^(2+)ions.Methods:A novel MgAP was developed on the basis of ionic crosslinking.Fourier transform infrared spectroscopy confirmed the chemical structure,whereas rheological analysis demonstrated stable mechanical properties and adaptability to dynamic loads.Sustained Mg^(2+)release was quantified over 7 days by inductively coupled plasma-mass spectrometry.In a rat acute myocardial infarction model,we performed echocardiography and strain analysis to assess cardiac function and histological staining to evaluate adverse remodeling.We also verified the proangiogenic effect through in vitro tube formation and in vivo immunofluorescence assays.Furthermore,transcriptomics and Western blotting were performed to explore the underlying mechanism.Additional assessments were also carried out in a rat model of lower limb ischemia.Results:Compared with intravenous administration of magnesium chloride,MgAP application effectively improved cardiac function and reduced adverse remodeling in the myocardial infarction rat model.The left ventricular ejection fraction increased by 20.3±6.6%,and the cardiac radial strain improved by 27.4±4.1%.The cardiac fibrosis area and cell apoptosis rate decreased by 10.9±1.2% and 32.1±5.5%,respectively.RNA sequencing analysis also highlighted the upregulation of genes related to cardiac electrophysiological properties,structural and functional intercellular connections,and revascularization.The increased gap junction protein expression and restored local blood supply could contribute to the cardiac repair process posttreatment.The proangiogenic effect of MgAP was also observed in the rat limb ischemia model.Conclusions:The above results revealed the convincing vascular regeneration effect of an ion therapy-based hydrogel,which enabled the local delivery of Mg^(2+)to the targeted ischemic tissue,aiding in cardiac and lower limb repair.This study presents a novel strategy and highlights its potential for use across various ischemic conditions.
基金sponsored by the National Natural Science Foundation of China(Grant Nos.51672184,81930070,81622032 and 81501858)the Natural Science Research of Jiangsu Higher Education Institutions(No.17KJA180011)the Jiangsu Innovation and Entrepreneur-ship Program,and the Priority Academice Program Development of Jiangsu High Education Institutions(PAPD).
文摘Severe skin wounds cause great problems and sufferings to patients.In this study,an injectable wound dressing based on strontium ion cross-linked starch hydrogel(SSH)was developed and evaluated.The good inject-ability of SSH made it easy to be delivered onto the wound surface.The good tissue adhesiveness of SSH ensured a firm protection of the wound.Besides,SSH supported the proliferation of NIH/3T3 fibroblasts and facilitated the migration of human umbilical vein endothelial cells(HUVECs).Importantly,SSH exhibited strong antibacterial effects on Staphylococcus aiireiis(S.ai/rec/s),which could prevent wound infection.These results demonstrate that SSH is a promising wound dressing material for promoting wound healing.
