Chronic diabetic wounds confront a significant medical challenge because of increasing prevalence and difficult-healing circumstances.It is vital to develop multifunctional hydrogel dressings,with well-designed morpho...Chronic diabetic wounds confront a significant medical challenge because of increasing prevalence and difficult-healing circumstances.It is vital to develop multifunctional hydrogel dressings,with well-designed morphology and structure to enhance flexibility and effectiveness in wound management.To achieve these,we propose a self-healing hydrogel dressing based on structural color microspheres for wound management.The microsphere comprised a photothermal-responsive inverse opal framework,which was constructed by hyaluronic acid methacryloyl,silk fibroin methacryloyl and black phosphorus quantum dots(BPQDs),and was further re-filled with a dynamic hydrogel.The dynamic hydrogel filler was formed by Knoevenagel condensation reaction between cyanoacetate and benzaldehyde-functionalized dextran(DEX-CA and DEX-BA).Notably,the composite microspheres can be applied arbitrarily,and they can adhere together upon near-infrared irradiation by leveraging the BPQDs-mediated photothermal effect and the thermoreversible stiffness change of dynamic hydrogel.Additionally,eumenitin and vascular endothelial growth factor were co-loaded in the microspheres and their release behavior can be regulated by the same mechanism.Moreover,effective monitoring of the drug release process can be achieved through visual color variations.The microsphere system has demonstrated desired capabilities of controllable drug release and efficient wound management.These characteristics suggest broad prospects for the proposed composite microspheres in clinical applications.展开更多
Gene therapy provides a promising approach in treating cancers with high efficacy and selectivity and few adverse effects.Currently,the development of functional vectors with safety and effectiveness is the intense fo...Gene therapy provides a promising approach in treating cancers with high efficacy and selectivity and few adverse effects.Currently,the development of functional vectors with safety and effectiveness is the intense focus for improving the delivery of nucleic acid drugs for gene therapy.For this purpose,stimuli-responsive nanocarriers displayed strong potential in improving the overall efficiencies of gene therapy and reducing adverse effects via effective protection,prolonged blood circulation,specific tumor accumulation,and controlled release profile of nucleic acid drugs.Besides,synergistic therapy could be achieved when combined with other therapeutic regimens.This review summarizes recent advances in various stimuliresponsive nanocarriers for gene delivery.Particularly,the nanocarriers responding to endogenous stimuli including pH,reactive oxygen species,glutathione,and enzyme,etc.,and exogenous stimuli including light,thermo,ultrasound,magnetic field,etc.,are introduced.Finally,the future challenges and prospects of stimuli-responsive gene delivery nanocarriers toward potential clinical translation are well discussed.The major objective of this review is to present the biomedical potential of stimuli-responsive gene delivery nanocarriers for cancer therapy and provide guidance for developing novel nanoplatforms that are clinically applicable.展开更多
Three-dimensional(3D)printing,referring to a type of additive manufacturing,has emerged as a promising fabrication technique in the past decades since it can create 3D objects with desired architecture by precise cont...Three-dimensional(3D)printing,referring to a type of additive manufacturing,has emerged as a promising fabrication technique in the past decades since it can create 3D objects with desired architecture by precise control over the deposition of successive layers of various materials.Benefiting from these advantages,3D printing has been extensively applied in varied areas of science and engineering.展开更多
Bone defects caused by trauma,tumor,or osteoarthritis remain challenging due to the lack of effective treatments in clinic.Stem cell transplantation has emerged as an alternative approach for bone repair and attracted...Bone defects caused by trauma,tumor,or osteoarthritis remain challenging due to the lack of effective treatments in clinic.Stem cell transplantation has emerged as an alternative approach for bone repair and attracted widespread attention owing to its excellent biological activities and therapy effect.The attempts to develop this therapeutic approach focus on the generation of effective cell delivery vehicles,since the shortcomings of direct injection of stem cells into target tissues.Here,we developed a novel core-shell microcapsule with a stem cell-laden core and a biomass shell by using all-aqueous phase microfluidic electrospray technology.The designed core-shell microcapsules showed a high cell viability during the culture procedure.In addition,the animal experiments exhibited that stem cell-laden core-shell microcapsules have good biocompatibility and therapeutic effect for bone defects.This study indicated that the core-shell biomass microcapsules generated by microfluidic electrospray have promising potential in tissue engineering and regenerative medicine.展开更多
Owing to its photonic band gap(PBG)and slow light effects,aniline black(AB)-poly(vinylidene fluoride)(PVDF)inverse opal(IO)photonic crystal(PC)was constructed to promote the utility of light and realize photothermal s...Owing to its photonic band gap(PBG)and slow light effects,aniline black(AB)-poly(vinylidene fluoride)(PVDF)inverse opal(IO)photonic crystal(PC)was constructed to promote the utility of light and realize photothermal synergetic catalysis.As a highly efficient reaction platform with the capability of restricting heat,a microreactor was introduced to further amplify the photothermal effects of near infrared(NIR)radiation.The photocatalytic efficiency of ZnO/0.5AB-PVDF IO(Z0.5A)increases 1.63-fold compared to that of pure ZnO film under a full solar spectrum,indicating the effectiveness of synergetic promotion by slow light and photothermal effects.Moreover,a 5.85-fold increase is achieved by combining Z0.5A with a microreactor compared to the film in a beaker.The photon localization effect of PVDF IO was further exemplified by finite-difference time-domain(FDTD)calculations.In conclusion,photonic crystal-microreactor enhanced photothermal catalysis has immense potential for alleviating the deteriorating water environment.展开更多
Recently,organ-on-chips have become a fast-growing research field with the widespread development of microfluidic chips and synthetic materials in tissue engineering.Due to the existing cardiotoxicity of many cardiova...Recently,organ-on-chips have become a fast-growing research field with the widespread development of microfluidic chips and synthetic materials in tissue engineering.Due to the existing cardiotoxicity of many cardiovascular drugs,heart-onchips which are promising to replace traditional animal models have been extensively researched and developed to mimic human organ functions in vitro.The heart-on-chips mainly focus on cardiac mechanics,which is regarded as the central indicator of in vitro heart models and drug testing.Traditional methods for the detection of myocardial mechanics have been demonstrated complex and inefficient in heart-on-chips.Therefore,photonic crystal materials with unique optical properties have attracted interests and have been introduced into the heart-on-chips,developing a visualized self-reporting system for cardiomyocytes activity monitoring.In this review,photonic crystal-based heart-on-chips for biosensing are introduced,as well as the fabricationmethods and design criteria of them.The characterizations of the photonic crystal materials are classified into optical properties and structural properties,and their applications in cell culture and biosensing are further discussed.Then,several representative examples and developments of the integration of photonic crystal materials into microfluidic chips are described in detail.Finally,potentials and limitations are put forward to promote the development of the photonic crystal-based intelligent heart-on-chips.展开更多
Drug resistance is one of the major obstacles in the drug therapy of cancers.Efforts in this area in pre-clinical research have focused on developing novel platforms to evaluate and decrease drug resistance.In this pa...Drug resistance is one of the major obstacles in the drug therapy of cancers.Efforts in this area in pre-clinical research have focused on developing novel platforms to evaluate and decrease drug resistance.In this paper,inspired by the structure of hives where swarms live and breed,we propose porous hydrogel arrays with a uniform pore structure for the generation of hepatoma cell spheroids and the investigation of drug resistance.The porous hydrogel arrays were fabricated using polyeth-ylene glycol diacrylate(PEGDA)hydrogel to negatively replicate a well-designed template.Benefiting from the elaborate processing of the template,the prepared porous hydrogel arrays possessed a uniform pore structure.Due to their anti-adhesion properties and the excellent biocompatibility of the PEGDA hydrogel,the hepatoma cells could form well-defined and uni-form hepatoma cell spheroids in the porous hydrogel arrays.We found that the resistant hepatoma cell spheroids showed more significant Lenvatinib resistance and a migratory phenotype compared with a two-dimensional(2D)cell culture,which reveals the reason for the failure of most 2D cell-selected drugs for in vivo applications.These features give such porous hydrogel arrays promising application prospects in the investigation of tumor cell spheroid culture and in vitro drug resistance.展开更多
Additive manufacturing plays a vital role in the food,mechanical,pharmaceutical,and medical fields.Within these fields,medical additive manufacturing has led to especially obvious improvements in medical instruments,p...Additive manufacturing plays a vital role in the food,mechanical,pharmaceutical,and medical fields.Within these fields,medical additive manufacturing has led to especially obvious improvements in medical instruments,prostheses,implants,and so forth,based on the advantages of cost-effectiveness,customizability,and quick manufacturing.With the features of precise structural control,high throughput,and good component manipulation,microfluidic techniques present distinctive benefits in medical additive manufacturing and have been applied in the areas of drug discovery,tissue engineering,and organs on chips.Thus,a comprehensive review of microfluidic techniques for medical additive manufacturing is useful for scientists with various backgrounds.Herein,we review recent progress in the development of microfluidic techniques for medical additive manufacturing.We evaluate the distinctive benefits associated with microfluidic technologies for medical additive manufacturing with respect to the fabrication of droplet/fiber templates with different structures.Extensive applications of microfluidic techniques for medical additive manufacturing are emphasized,such as cell guidance,three-dimensional(3D)cell culture,tissue assembly,and cell-based therapy.Finally,we present challenges in and future perspectives on the development of microfluidics for medical additive manufacturing.展开更多
1.Research and development(R&D)and the challenges of raw materials for medical additive manufacturing Raw materials for medical additive manufacturing have a wide range of commonalities that are also seen in many ...1.Research and development(R&D)and the challenges of raw materials for medical additive manufacturing Raw materials for medical additive manufacturing have a wide range of commonalities that are also seen in many other fields,making them an important basis in the field of three-dimensional(3D)printing.Problems and challenges related to material types,powder properties,formability,viscoelasticity,and so forth also share common features.For example,many metal materials are used in the field of aviation,while metals,polymers,and inorganic materials are used in the field of biomedicine.The most widely used materials in biomedicine are biocompatible.Various homogeneous and non-homogeneous composites are also available for 3D printing,and impose an additional challenge in additive manufacturing;the use of heterogeneous composites in 3D printing is particularly challenging.展开更多
Soft biomaterials hold great potential for a plethora of biomedical applications because of their deforma-bility,biodegradability,biocompatibility,high bioactivity,and low antigenicity.Multicomponent soft bio-material...Soft biomaterials hold great potential for a plethora of biomedical applications because of their deforma-bility,biodegradability,biocompatibility,high bioactivity,and low antigenicity.Multicomponent soft bio-materials are particularly attractive as a way of accommodating components made of different materials and generating combinative functions.Microfluidic technology has emerged as an outstanding tool in generating multicomponent materials with elaborate structures and constituents,in that it can manipu-late multiphasic flows precisely on the micron scale.In recent decades,much progress has been achieved in the microfluidic fabrication of multicomponent soft biomaterials with finely defined physicochemical properties capable of controllable therapeutics delivery,three-dimensional(3D)cell culture,flexible devices and wearable electronics,and biosensing for molecules.In the paper,we summarize current pro-gress in multicomponent soft biomaterials derived from microfluidics and emphasize their applications in biomedical fields.We also provide an outlook of the remaining challenges and future trends in this field.展开更多
With the advantages of better mimicking the specificity of natural tissues,three-dimensional(3D)cell culture plays a major role in drug development,toxicity testing,and tissue engineering.However,existing scaffolds or...With the advantages of better mimicking the specificity of natural tissues,three-dimensional(3D)cell culture plays a major role in drug development,toxicity testing,and tissue engineering.However,existing scaffolds or microcarriers for 3D cell culture are often limited in size and show suboptimal performance in simulating the vascular complexes of living organisms.Therefore,we present a novel hierarchically inverse opal porous scaffold made via a simple microfluidic approach for promoting 3D cell co-culture techniques.The designed scaffold is constructed using a combined concept involving an emulsion droplet template and inert polymer polymerization.This work demonstrates that the resultant scaffolds ensure a sufficient supply of nutrients during cell culture,so as to achieve large-volume cell culture.In addition,by serially planting different cells in the scaffold,a 3D co-culture system of endothelial-cellencapsulated hepatocytes can be developed for constructing certain functional tissues.It is also demonstrated that the use of the proposed scaffold for a co-culture system helps hepatocytes to maintain specific in vivo functions.These hierarchically inverse opal scaffolds lay the foundation for 3D cell culture and even the construction of biomimetic tissues.展开更多
Stem cell therapy holds immense potential as a viable treatment for a widespread range of intractable disorders.As the safety of stem cell transplantation having been demonstrated in numerous clinical trials,various k...Stem cell therapy holds immense potential as a viable treatment for a widespread range of intractable disorders.As the safety of stem cell transplantation having been demonstrated in numerous clinical trials,various kinds of stem cells are currently utilized in medical applications.Despite the achievements,the therapeutic benefits of stem cells for diseases are limited,and the data of clinical researches are unstable.To optimize tthe effectiveness of stem cells,engineering approaches have been developed to enhance their inherent abilities and impart them with new functionalities,paving the way for the next generation of stem cell therapies.This review offers a detailed analysis of engineered stem cells,including their clinical applications and potential for future development.We begin by briefly introducing the recent advances in the production of stem cells(induced pluripotent stem cells(ipsCs),embryonic stem cells(ESCs),mesenchymal stem cells(MSCs)and hematopoietic stem cells(HSCs).Furthermore,we present the latest developments of engineered strategies in stem cells,including engineered methods in molecular biology and biomaterial fields,and their application in biomedical research.Finally,we summarize the current obstacles and suggest future prospects for engineered stem cells in clinical translations and biomedical applications.展开更多
Natural polymers are complex organic molecules that occur in the natural environment and have not been subjected to artificial synthesis.They are frequently encountered in various creatures,including mammals,plants,an...Natural polymers are complex organic molecules that occur in the natural environment and have not been subjected to artificial synthesis.They are frequently encountered in various creatures,including mammals,plants,and microbes.The aforementioned polymers are commonly derived from renewable sources,possess a notable level of compatibility with living organisms,and have a limited adverse effect on the environment.As a result,they hold considerable significance in the development of sustainable and environmentally friendly goods.In recent times,there has been notable advancement in the investigation of the potential uses of natural polymers in the field of biomedicine,specifically in relation to natural biomaterials that exhibit antibacterial and antioxidant characteristics.This review provides a comprehensive overview of prevalent natural polymers utilized in the biomedical domain throughout the preceding two decades.In this paper,we present a comprehensive examination of the components and typical methods for the preparation of biomaterials based on natural polymers.Furthermore,we summarize the application of natural polymer materials in each stage of skin wound repair.Finally,we present key findings and insights into the limitations of current natural polymers and elucidate the prospects for their future development in this field.展开更多
Macrophages play a pivotal role in systemic lupus erythematosus(SLE)therapy.Efforts have been made to develop multifunctional drug delivery systems capable of directing macrophage polarization.Here,we present a novel ...Macrophages play a pivotal role in systemic lupus erythematosus(SLE)therapy.Efforts have been made to develop multifunctional drug delivery systems capable of directing macrophage polarization.Here,we present a novel hyaluronic acid methacrylate(HAMA)hydrogel microparticle encapsulating multiple cytokines for SLE remission though enhancing macrophage functions.The HAMA microparticles loaded with monocyte chemotactic protein-1(MCP-1)and interleukin-4(IL-4)were fabricated by using a microfluidic technology.The released MCP-1 facilitates the aggregation of inflammatory macrophages,after which IL-4 induces the macrophage phenotype shift from inflammatory M1 to immune-protective M2,thus restoring immune balance.We have demonstrated in MRL/lpr mice that the hydrogel microparticles could improve their efficacy of intraperitoneal drug delivery,modulate immune function,and attenuate the disease symptoms.These results suggest that our proposed microparticles delivery platform has potential clinical value for treating autoimmune diseases.展开更多
Considerable efforts have been devoted to treating gastric ulcers.Attempts in this field tend to develop drug delivery systems with prolonged gastric retention time.Herein,we develop novel Chinese herb pollen-derived ...Considerable efforts have been devoted to treating gastric ulcers.Attempts in this field tend to develop drug delivery systems with prolonged gastric retention time.Herein,we develop novel Chinese herb pollen-derived micromotors as active oral drug delivery system for treating gastric ulcer.Such Chinese herb pollen-derived micromotors are simply produced by asymmetrically sputtering Mg layer onto one side of pollen grains.When exposed to gastric juice,the Mg layer can react with the hydrogen ions,resulting in intensive generation of hydrogen bubbles to propel the micromotors.Benefiting from the autonomous motion and unique spiny structure,our micromotors can move actively in the stomach and adhere to the surrounding tissues.Besides,their special architecture endows the micromotors with salient capacity of drug loading and releasing.Based on these features,we have demonstrated that our Chinese herb pollen-derived micromotors could effective deliver berberine hydrochloride and show desirable curative effect on the gastric ulcer model of mice.Therefore,these Chinese herb pollen-derived micromotors are anticipated to serve as promising oral drug delivery carriers for clinical applications.展开更多
Complete wound healing without scar formation has attracted increasing attention,prompting the development of various strategies to address this challenge.In clinical settings,there is a growing preference for emergin...Complete wound healing without scar formation has attracted increasing attention,prompting the development of various strategies to address this challenge.In clinical settings,there is a growing preference for emerging biomedical technologies that effectively manage fibrosis following skin injury,as they provide high efficacy,cost-effectiveness,and minimal side effects compared to invasive and costly surgical techniques.This review gives an overview of the latest developments in advanced biomedical technologies for scarless wound management.We first introduce the wound healing process and key mechanisms involved in scar formation.Subsequently,we explore common strategies for wound treatment,including their fabrication methods,superior performance and the latest research developments in this field.We then shift our focus to emerging biomedical technologies for scarless wound healing,detailing the mechanism of action,unique properties,and advanced practical applications of various biomedical technology-based therapies,such as cell therapy,drug therapy,biomaterial therapy,and synergistic therapy.Finally,we critically assess the shortcomings and potential applications of these biomedical technologies and therapeutic methods in the realm of scar treatment.展开更多
The management of infected wounds is always of great significance and urgency in clinical and biomedicalfields.Recent efforts in this area are focusing on the development of functional wound patches with effective antib...The management of infected wounds is always of great significance and urgency in clinical and biomedicalfields.Recent efforts in this area are focusing on the development of functional wound patches with effective antibacterial,drug delivery,and sensor properties.Here,we present novel hyaluronic acid(HA)microneedle patches with these features by encapsulating aminobenzeneboronic acid-modified gold nanoclusters(A-GNCs)for infected wound management.The A-GNCs loaded microneedle patches were derived from negative-mold replication and showed high mechanical strength to penetrate the skin.The release of the A-GNCs was realized by the degradation of HA,and the self-monitor of the released actives was based on the dynamic bright orangefluorescence emitted from A-GNCs under ultravio-let radiation.As the A-GNCs could destroy bacteria membranes,the microneedle patches were with excellent in vitro antibiosis ability.Based on these features,we have demonstrated the bacteria inhibition,residual drug self-monitoring,and wound healing promotion abilities of the microneedle patches in Escherichia coli-or Staphylococcus aureus-infected wound management.These results indicated the great potential of such A-GNCs loaded microneedle patches for clinical applications.展开更多
The controllable manipulation and transfer of droplets are fundamental in a wide range of chemical reactions and even life processes. Herein, we present a novel, universal, and straightforward acoustic approach to fab...The controllable manipulation and transfer of droplets are fundamental in a wide range of chemical reactions and even life processes. Herein, we present a novel, universal, and straightforward acoustic approach to fabricating biomimetic surfaces for on-demand droplet manipulations like many natural creatures. Based on the capillary waves induced by surface acoustic waves, various polymer films could be deformed into pre-designed structures, such as parallel grooves and grid-like patterns. These structured and functionalized surfaces exhibit impressive ability in droplet transportation and water collection, respectively. Besides these static surfaces, the tunability of acoustics could also endow polymer surfaces with dynamic controllability for droplet manipulations, including programming wettability, mitigating droplet evaporation, and accelerating chemical reactions. Our approach is capable of achieving universal surface manufacturing and droplet manipulation simultaneously, which simplifies the fabrication process and eliminates the need for additional chemical modifications. Thus, we believe that our acoustic-derived surfaces and technologies could provide a unique perspective for various applications, including microreactor integration, biochemical reaction control, tissue engineering, and so on.展开更多
Biological scaffolds have been widely employed in wound healing applications,while their practical efficiency is compromised by insufficient oxygen delivery to the 3-dimensional constructs and inadequate nutrient supp...Biological scaffolds have been widely employed in wound healing applications,while their practical efficiency is compromised by insufficient oxygen delivery to the 3-dimensional constructs and inadequate nutrient supply for the long-term healing process.Here,we present an innovative living Chinese herbal scaffold to provide a sustainable oxygen and nutrient supply for promoting wound healing.Through a facile microfluidic bioprinting strategy,a traditional Chinese herbal medicine(Panax notoginseng saponins[PNS])and a living autotrophic microorganism(microalgae Chlorella pyrenoidosa[MA])were successfully encapsulated into the scaffolds.The encapsulated PNS could be gradually released from the scaffolds,which promoted cell adhesion,proliferation,migration,and tube formation in vitro.In addition,benefiting from the photosynthetic oxygenation of the alive MA,the obtained scaffolds would produce sustainable oxygen under light illumination,exerting a protective effect against hypoxia-induced cell death.Based on these features,we have demonstrated through in vivo experiments that these living Chinese herbal scaffolds could efficiently alleviate local hypoxia,enhance angiogenesis,and thereby accelerate wound closure in diabetic mice,indicating their great potential in wound healing and other tissue repair applications.展开更多
基金supported by the Ruijin Hospital Guangci Introducing Talent Projectfinancial support from National Natural Science Foundation of China(82372145)+4 种基金the Research Fellow(Grant No.353146)Research Project(347897)Solutions for Health Profile(336355)InFLAMES Flagship(337531)grants from Academy of Finlandthe Finland China Food and Health International Pilot Project funded by the Finnish Ministry of Education and Culture.
文摘Chronic diabetic wounds confront a significant medical challenge because of increasing prevalence and difficult-healing circumstances.It is vital to develop multifunctional hydrogel dressings,with well-designed morphology and structure to enhance flexibility and effectiveness in wound management.To achieve these,we propose a self-healing hydrogel dressing based on structural color microspheres for wound management.The microsphere comprised a photothermal-responsive inverse opal framework,which was constructed by hyaluronic acid methacryloyl,silk fibroin methacryloyl and black phosphorus quantum dots(BPQDs),and was further re-filled with a dynamic hydrogel.The dynamic hydrogel filler was formed by Knoevenagel condensation reaction between cyanoacetate and benzaldehyde-functionalized dextran(DEX-CA and DEX-BA).Notably,the composite microspheres can be applied arbitrarily,and they can adhere together upon near-infrared irradiation by leveraging the BPQDs-mediated photothermal effect and the thermoreversible stiffness change of dynamic hydrogel.Additionally,eumenitin and vascular endothelial growth factor were co-loaded in the microspheres and their release behavior can be regulated by the same mechanism.Moreover,effective monitoring of the drug release process can be achieved through visual color variations.The microsphere system has demonstrated desired capabilities of controllable drug release and efficient wound management.These characteristics suggest broad prospects for the proposed composite microspheres in clinical applications.
基金the financial support from the National Key Research and Development Program of China(2020YFA0908200)the National Natural Science Foundation of China(52103196 and 52073060)+1 种基金Guangdong Basic and Applied Basic Research Foundation(2021B1515120054)the Shenzhen Fundamental Research Program(JCYJ20190813152616459 and JCYJ20210324133214038)。
文摘Gene therapy provides a promising approach in treating cancers with high efficacy and selectivity and few adverse effects.Currently,the development of functional vectors with safety and effectiveness is the intense focus for improving the delivery of nucleic acid drugs for gene therapy.For this purpose,stimuli-responsive nanocarriers displayed strong potential in improving the overall efficiencies of gene therapy and reducing adverse effects via effective protection,prolonged blood circulation,specific tumor accumulation,and controlled release profile of nucleic acid drugs.Besides,synergistic therapy could be achieved when combined with other therapeutic regimens.This review summarizes recent advances in various stimuliresponsive nanocarriers for gene delivery.Particularly,the nanocarriers responding to endogenous stimuli including pH,reactive oxygen species,glutathione,and enzyme,etc.,and exogenous stimuli including light,thermo,ultrasound,magnetic field,etc.,are introduced.Finally,the future challenges and prospects of stimuli-responsive gene delivery nanocarriers toward potential clinical translation are well discussed.The major objective of this review is to present the biomedical potential of stimuli-responsive gene delivery nanocarriers for cancer therapy and provide guidance for developing novel nanoplatforms that are clinically applicable.
基金This work was supported by the National Key Research and Development Program of China(2020YFA0908200)the National Natural Science Foundation of China(82101184 and 21902024)+2 种基金the Shenzhen Fundamental Research Program(JCYJ20210324102809024,JCYJ20190813152616459,and JCYJ20210324133214038)the Shenzhen Ph.D.Start-up Program(RCBS20210609103713045)the Guangdong Basic and Applied Basic Research Foundation(2020A1515110780 and 2021B1515120054).
文摘Three-dimensional(3D)printing,referring to a type of additive manufacturing,has emerged as a promising fabrication technique in the past decades since it can create 3D objects with desired architecture by precise control over the deposition of successive layers of various materials.Benefiting from these advantages,3D printing has been extensively applied in varied areas of science and engineering.
基金supported by the National Key Research and Development Program of China(2020YFA0908200)the National Natural Science Foundation of China(52073060 and 61927805)the Shenzhen Fundamental Research Program(JCYJ20190813152616459).
文摘Bone defects caused by trauma,tumor,or osteoarthritis remain challenging due to the lack of effective treatments in clinic.Stem cell transplantation has emerged as an alternative approach for bone repair and attracted widespread attention owing to its excellent biological activities and therapy effect.The attempts to develop this therapeutic approach focus on the generation of effective cell delivery vehicles,since the shortcomings of direct injection of stem cells into target tissues.Here,we developed a novel core-shell microcapsule with a stem cell-laden core and a biomass shell by using all-aqueous phase microfluidic electrospray technology.The designed core-shell microcapsules showed a high cell viability during the culture procedure.In addition,the animal experiments exhibited that stem cell-laden core-shell microcapsules have good biocompatibility and therapeutic effect for bone defects.This study indicated that the core-shell biomass microcapsules generated by microfluidic electrospray have promising potential in tissue engineering and regenerative medicine.
文摘Owing to its photonic band gap(PBG)and slow light effects,aniline black(AB)-poly(vinylidene fluoride)(PVDF)inverse opal(IO)photonic crystal(PC)was constructed to promote the utility of light and realize photothermal synergetic catalysis.As a highly efficient reaction platform with the capability of restricting heat,a microreactor was introduced to further amplify the photothermal effects of near infrared(NIR)radiation.The photocatalytic efficiency of ZnO/0.5AB-PVDF IO(Z0.5A)increases 1.63-fold compared to that of pure ZnO film under a full solar spectrum,indicating the effectiveness of synergetic promotion by slow light and photothermal effects.Moreover,a 5.85-fold increase is achieved by combining Z0.5A with a microreactor compared to the film in a beaker.The photon localization effect of PVDF IO was further exemplified by finite-difference time-domain(FDTD)calculations.In conclusion,photonic crystal-microreactor enhanced photothermal catalysis has immense potential for alleviating the deteriorating water environment.
基金This work was supported by the National Natural Science Foundation of China(Grants 61927805)the Natural Science Foundation of Jiangsu(Grant No.BE2018707)the Scientific Research Foundation of Nanjing University and Drum Tower Hospital.
文摘Recently,organ-on-chips have become a fast-growing research field with the widespread development of microfluidic chips and synthetic materials in tissue engineering.Due to the existing cardiotoxicity of many cardiovascular drugs,heart-onchips which are promising to replace traditional animal models have been extensively researched and developed to mimic human organ functions in vitro.The heart-on-chips mainly focus on cardiac mechanics,which is regarded as the central indicator of in vitro heart models and drug testing.Traditional methods for the detection of myocardial mechanics have been demonstrated complex and inefficient in heart-on-chips.Therefore,photonic crystal materials with unique optical properties have attracted interests and have been introduced into the heart-on-chips,developing a visualized self-reporting system for cardiomyocytes activity monitoring.In this review,photonic crystal-based heart-on-chips for biosensing are introduced,as well as the fabricationmethods and design criteria of them.The characterizations of the photonic crystal materials are classified into optical properties and structural properties,and their applications in cell culture and biosensing are further discussed.Then,several representative examples and developments of the integration of photonic crystal materials into microfluidic chips are described in detail.Finally,potentials and limitations are put forward to promote the development of the photonic crystal-based intelligent heart-on-chips.
基金supported by the National Key Research and Development Program of China(No.2020YFA0908200)the National Natural Science Foundation of China(Nos.52073060,61927805,81974312,and 81501823)+5 种基金the Natural Science Foundation of Jiangsu Province(No.BE2018707)the Shenzhen Fundamental Research Program(No.JCYJ20190813152616459)the Zhejiang Provincial Natural Science Foundation of China(Nos.LY18H160049 and LQ19H160008)the Medical Scientific Research of Zhejiang Province(No.2017KY459)Wenzhou Municipal Science and Technology Bureau(No.Y20190203)Wenzhou Institute,University of Chinese Academy of Sciences’s startup fund(No.WIUCASQD2019007).
文摘Drug resistance is one of the major obstacles in the drug therapy of cancers.Efforts in this area in pre-clinical research have focused on developing novel platforms to evaluate and decrease drug resistance.In this paper,inspired by the structure of hives where swarms live and breed,we propose porous hydrogel arrays with a uniform pore structure for the generation of hepatoma cell spheroids and the investigation of drug resistance.The porous hydrogel arrays were fabricated using polyeth-ylene glycol diacrylate(PEGDA)hydrogel to negatively replicate a well-designed template.Benefiting from the elaborate processing of the template,the prepared porous hydrogel arrays possessed a uniform pore structure.Due to their anti-adhesion properties and the excellent biocompatibility of the PEGDA hydrogel,the hepatoma cells could form well-defined and uni-form hepatoma cell spheroids in the porous hydrogel arrays.We found that the resistant hepatoma cell spheroids showed more significant Lenvatinib resistance and a migratory phenotype compared with a two-dimensional(2D)cell culture,which reveals the reason for the failure of most 2D cell-selected drugs for in vivo applications.These features give such porous hydrogel arrays promising application prospects in the investigation of tumor cell spheroid culture and in vitro drug resistance.
基金This work was supported by the National Key Research and Development Program of China(2020YFA0908200)the National Natural Science Foundation of China(22002061,52073060,and 61927805)+1 种基金the Natural Science Foundation of Jiangsu(BE2018707)the Jiangsu Agricultural Science and Technology Innovation Fund(CX(20)3051).
文摘Additive manufacturing plays a vital role in the food,mechanical,pharmaceutical,and medical fields.Within these fields,medical additive manufacturing has led to especially obvious improvements in medical instruments,prostheses,implants,and so forth,based on the advantages of cost-effectiveness,customizability,and quick manufacturing.With the features of precise structural control,high throughput,and good component manipulation,microfluidic techniques present distinctive benefits in medical additive manufacturing and have been applied in the areas of drug discovery,tissue engineering,and organs on chips.Thus,a comprehensive review of microfluidic techniques for medical additive manufacturing is useful for scientists with various backgrounds.Herein,we review recent progress in the development of microfluidic techniques for medical additive manufacturing.We evaluate the distinctive benefits associated with microfluidic technologies for medical additive manufacturing with respect to the fabrication of droplet/fiber templates with different structures.Extensive applications of microfluidic techniques for medical additive manufacturing are emphasized,such as cell guidance,three-dimensional(3D)cell culture,tissue assembly,and cell-based therapy.Finally,we present challenges in and future perspectives on the development of microfluidics for medical additive manufacturing.
文摘1.Research and development(R&D)and the challenges of raw materials for medical additive manufacturing Raw materials for medical additive manufacturing have a wide range of commonalities that are also seen in many other fields,making them an important basis in the field of three-dimensional(3D)printing.Problems and challenges related to material types,powder properties,formability,viscoelasticity,and so forth also share common features.For example,many metal materials are used in the field of aviation,while metals,polymers,and inorganic materials are used in the field of biomedicine.The most widely used materials in biomedicine are biocompatible.Various homogeneous and non-homogeneous composites are also available for 3D printing,and impose an additional challenge in additive manufacturing;the use of heterogeneous composites in 3D printing is particularly challenging.
基金supported by the National Key Research and Development Program of China (2020YFA0908200)the National Natural Science Foundation of China (22002018, 52073060, and61927805)the Shenzhen Fundamental Research Program(JCYJ20190813152616459 and JCYJ20210324133214038)
文摘Soft biomaterials hold great potential for a plethora of biomedical applications because of their deforma-bility,biodegradability,biocompatibility,high bioactivity,and low antigenicity.Multicomponent soft bio-materials are particularly attractive as a way of accommodating components made of different materials and generating combinative functions.Microfluidic technology has emerged as an outstanding tool in generating multicomponent materials with elaborate structures and constituents,in that it can manipu-late multiphasic flows precisely on the micron scale.In recent decades,much progress has been achieved in the microfluidic fabrication of multicomponent soft biomaterials with finely defined physicochemical properties capable of controllable therapeutics delivery,three-dimensional(3D)cell culture,flexible devices and wearable electronics,and biosensing for molecules.In the paper,we summarize current pro-gress in multicomponent soft biomaterials derived from microfluidics and emphasize their applications in biomedical fields.We also provide an outlook of the remaining challenges and future trends in this field.
基金the National Key Research and Development Program of China(2020YFA0908200)the National Natural Science Foundation of China(52073060,32101159,and 61927805)+1 种基金the Shenzhen Fundamental Research Program(JCYJ20190813152616459)the Wenzhou Institute,University of Chinese Academy of Sciences(WIUCAS)’startup fund(WIUCASQD2019007).
文摘With the advantages of better mimicking the specificity of natural tissues,three-dimensional(3D)cell culture plays a major role in drug development,toxicity testing,and tissue engineering.However,existing scaffolds or microcarriers for 3D cell culture are often limited in size and show suboptimal performance in simulating the vascular complexes of living organisms.Therefore,we present a novel hierarchically inverse opal porous scaffold made via a simple microfluidic approach for promoting 3D cell co-culture techniques.The designed scaffold is constructed using a combined concept involving an emulsion droplet template and inert polymer polymerization.This work demonstrates that the resultant scaffolds ensure a sufficient supply of nutrients during cell culture,so as to achieve large-volume cell culture.In addition,by serially planting different cells in the scaffold,a 3D co-culture system of endothelial-cellencapsulated hepatocytes can be developed for constructing certain functional tissues.It is also demonstrated that the use of the proposed scaffold for a co-culture system helps hepatocytes to maintain specific in vivo functions.These hierarchically inverse opal scaffolds lay the foundation for 3D cell culture and even the construction of biomimetic tissues.
基金supported by the National Key Research and Development Program of China(2022YFA1105300)the National Natural Science Foundation of China(T2225003,82100664,and 82270646)+5 种基金the Jiangsu Provincial Science and Technology Special Fund for Outstanding Young Scholars(BK20230051)the Nanjing Health Science and Technology Development Project for Distinguished Young Scholars(JQX22003)fundings for Clinical Trials from the Affiliated Drum Tower Hospital,Medical School of Nanjing University(2021-LCYJ-PY-46,2022-LCYJ-PY-35)the Nanjing Medical Science and Technique Development Foundation(ZKX21019)Guangdong Basic and Applied Basic Research Foundation(2021B1515120054)the Shenzhen Science and Technology Program(JCYJ20210324133214038 and JCYJ20190813152616459).
文摘Stem cell therapy holds immense potential as a viable treatment for a widespread range of intractable disorders.As the safety of stem cell transplantation having been demonstrated in numerous clinical trials,various kinds of stem cells are currently utilized in medical applications.Despite the achievements,the therapeutic benefits of stem cells for diseases are limited,and the data of clinical researches are unstable.To optimize tthe effectiveness of stem cells,engineering approaches have been developed to enhance their inherent abilities and impart them with new functionalities,paving the way for the next generation of stem cell therapies.This review offers a detailed analysis of engineered stem cells,including their clinical applications and potential for future development.We begin by briefly introducing the recent advances in the production of stem cells(induced pluripotent stem cells(ipsCs),embryonic stem cells(ESCs),mesenchymal stem cells(MSCs)and hematopoietic stem cells(HSCs).Furthermore,we present the latest developments of engineered strategies in stem cells,including engineered methods in molecular biology and biomaterial fields,and their application in biomedical research.Finally,we summarize the current obstacles and suggest future prospects for engineered stem cells in clinical translations and biomedical applications.
基金supported by the National Key Research and Development Program of China(2020YFA0908200)the National Natural Science Foundation of China(T2225003,52073060 and 61927805)+3 种基金the Nanjing Medical Science and Technique Development Foundation(ZKX21019)the Clinical Trials from Nanjing Drum Tower Hospital(2022-LCYJ-ZD-01)Guangdong Basic and Applied Basic Research Foundation(2021B1515120054)the Shenzhen Fundamental Research Program(JCYJ20210324133214038).
文摘Natural polymers are complex organic molecules that occur in the natural environment and have not been subjected to artificial synthesis.They are frequently encountered in various creatures,including mammals,plants,and microbes.The aforementioned polymers are commonly derived from renewable sources,possess a notable level of compatibility with living organisms,and have a limited adverse effect on the environment.As a result,they hold considerable significance in the development of sustainable and environmentally friendly goods.In recent times,there has been notable advancement in the investigation of the potential uses of natural polymers in the field of biomedicine,specifically in relation to natural biomaterials that exhibit antibacterial and antioxidant characteristics.This review provides a comprehensive overview of prevalent natural polymers utilized in the biomedical domain throughout the preceding two decades.In this paper,we present a comprehensive examination of the components and typical methods for the preparation of biomaterials based on natural polymers.Furthermore,we summarize the application of natural polymer materials in each stage of skin wound repair.Finally,we present key findings and insights into the limitations of current natural polymers and elucidate the prospects for their future development in this field.
基金supported by the National Key Research and Development Program of China(No.2020YFA0908200)the Key Program of National Natural Science Foundation of China(Nos.81930043,and 82330055)the National Natural Science Foundation of China(Nos.52073060,and 81720108022).
文摘Macrophages play a pivotal role in systemic lupus erythematosus(SLE)therapy.Efforts have been made to develop multifunctional drug delivery systems capable of directing macrophage polarization.Here,we present a novel hyaluronic acid methacrylate(HAMA)hydrogel microparticle encapsulating multiple cytokines for SLE remission though enhancing macrophage functions.The HAMA microparticles loaded with monocyte chemotactic protein-1(MCP-1)and interleukin-4(IL-4)were fabricated by using a microfluidic technology.The released MCP-1 facilitates the aggregation of inflammatory macrophages,after which IL-4 induces the macrophage phenotype shift from inflammatory M1 to immune-protective M2,thus restoring immune balance.We have demonstrated in MRL/lpr mice that the hydrogel microparticles could improve their efficacy of intraperitoneal drug delivery,modulate immune function,and attenuate the disease symptoms.These results suggest that our proposed microparticles delivery platform has potential clinical value for treating autoimmune diseases.
基金supported by the National Key Research and Development Program of China(2022YFA1105300)the National Natural Science Foundation of China(T2225003,52073060 and 61927805)+3 种基金the Nanjing Medical Science and Technique Development Foundation(ZKX21019)the Clinical Trials from Nanjing Drum Tower Hospital(2022-LCYJ-ZD-01)Guangdong Basic and Applied Basic Research Foundation(2021B1515120054)the Shenzhen Fundamental Research Program(JCYJ20190813152616459 and JCYJ20210324133214038).
文摘Considerable efforts have been devoted to treating gastric ulcers.Attempts in this field tend to develop drug delivery systems with prolonged gastric retention time.Herein,we develop novel Chinese herb pollen-derived micromotors as active oral drug delivery system for treating gastric ulcer.Such Chinese herb pollen-derived micromotors are simply produced by asymmetrically sputtering Mg layer onto one side of pollen grains.When exposed to gastric juice,the Mg layer can react with the hydrogen ions,resulting in intensive generation of hydrogen bubbles to propel the micromotors.Benefiting from the autonomous motion and unique spiny structure,our micromotors can move actively in the stomach and adhere to the surrounding tissues.Besides,their special architecture endows the micromotors with salient capacity of drug loading and releasing.Based on these features,we have demonstrated that our Chinese herb pollen-derived micromotors could effective deliver berberine hydrochloride and show desirable curative effect on the gastric ulcer model of mice.Therefore,these Chinese herb pollen-derived micromotors are anticipated to serve as promising oral drug delivery carriers for clinical applications.
基金supported by the National Key Research and Development Program of China(2022YFB4700100)the National Natural Science Foundation of China(T2225003,52073060 and 61927805)+3 种基金the Nanjing Medical Science and Technique Development Foundation(ZKX21019)the Clinical Trials from Nanjing Drum Tower Hospital(2022-LCYJ-ZD-01)Guangdong Basic and Applied Basic Research Foundation(2021B1515120054)the Shenzhen Science and Technology Program(JCYJ20210324133214038).
文摘Complete wound healing without scar formation has attracted increasing attention,prompting the development of various strategies to address this challenge.In clinical settings,there is a growing preference for emerging biomedical technologies that effectively manage fibrosis following skin injury,as they provide high efficacy,cost-effectiveness,and minimal side effects compared to invasive and costly surgical techniques.This review gives an overview of the latest developments in advanced biomedical technologies for scarless wound management.We first introduce the wound healing process and key mechanisms involved in scar formation.Subsequently,we explore common strategies for wound treatment,including their fabrication methods,superior performance and the latest research developments in this field.We then shift our focus to emerging biomedical technologies for scarless wound healing,detailing the mechanism of action,unique properties,and advanced practical applications of various biomedical technology-based therapies,such as cell therapy,drug therapy,biomaterial therapy,and synergistic therapy.Finally,we critically assess the shortcomings and potential applications of these biomedical technologies and therapeutic methods in the realm of scar treatment.
基金National Key Research and Development Program of China,Grant/Award Number:2020YFA0908200National Natural Science Foundation of China,Grant/Award Numbers:52073060,61927805+1 种基金Guangdong Basic and Applied Basic Research Foundation,Grant/Award Number:2021B1515120054Shenzhen Fundamental Research Program,Grant/Award Number:JCYJ20210324133214038。
文摘The management of infected wounds is always of great significance and urgency in clinical and biomedicalfields.Recent efforts in this area are focusing on the development of functional wound patches with effective antibacterial,drug delivery,and sensor properties.Here,we present novel hyaluronic acid(HA)microneedle patches with these features by encapsulating aminobenzeneboronic acid-modified gold nanoclusters(A-GNCs)for infected wound management.The A-GNCs loaded microneedle patches were derived from negative-mold replication and showed high mechanical strength to penetrate the skin.The release of the A-GNCs was realized by the degradation of HA,and the self-monitor of the released actives was based on the dynamic bright orangefluorescence emitted from A-GNCs under ultravio-let radiation.As the A-GNCs could destroy bacteria membranes,the microneedle patches were with excellent in vitro antibiosis ability.Based on these features,we have demonstrated the bacteria inhibition,residual drug self-monitoring,and wound healing promotion abilities of the microneedle patches in Escherichia coli-or Staphylococcus aureus-infected wound management.These results indicated the great potential of such A-GNCs loaded microneedle patches for clinical applications.
基金the National Key Research and Development Program of China (2020YFA0908200)the National Natural Science Foundation of China (T2225003, 52073060, and 81720108022)+3 种基金the Nanjing Medical Science and Technique Development Foundation (ZKX21019)the Clinical Trials from Nanjing Drum Tower Hospital (2022-LCYJ-ZD-01)the Guangdong Basic and Applied Basic Research Foundation (2021B1515120054)the Shenzhen Fundamental Research Program (JCYJ20190813152616459 and JCYJ20210324133214038).
文摘The controllable manipulation and transfer of droplets are fundamental in a wide range of chemical reactions and even life processes. Herein, we present a novel, universal, and straightforward acoustic approach to fabricating biomimetic surfaces for on-demand droplet manipulations like many natural creatures. Based on the capillary waves induced by surface acoustic waves, various polymer films could be deformed into pre-designed structures, such as parallel grooves and grid-like patterns. These structured and functionalized surfaces exhibit impressive ability in droplet transportation and water collection, respectively. Besides these static surfaces, the tunability of acoustics could also endow polymer surfaces with dynamic controllability for droplet manipulations, including programming wettability, mitigating droplet evaporation, and accelerating chemical reactions. Our approach is capable of achieving universal surface manufacturing and droplet manipulation simultaneously, which simplifies the fabrication process and eliminates the need for additional chemical modifications. Thus, we believe that our acoustic-derived surfaces and technologies could provide a unique perspective for various applications, including microreactor integration, biochemical reaction control, tissue engineering, and so on.
基金the National Key Research and Development Program of China(2020YFA0908200)the National Natural Science Foundation of China(32201117 and 52073060)+2 种基金the Guangdong Basic and Applied Basic Research Foundation(2021B1515120054)the Shenzhen Fundamental Research Program(JCYJ20190813152616459)the fellowship of China Postdoctoral Science Foundation(2021M700141)。
文摘Biological scaffolds have been widely employed in wound healing applications,while their practical efficiency is compromised by insufficient oxygen delivery to the 3-dimensional constructs and inadequate nutrient supply for the long-term healing process.Here,we present an innovative living Chinese herbal scaffold to provide a sustainable oxygen and nutrient supply for promoting wound healing.Through a facile microfluidic bioprinting strategy,a traditional Chinese herbal medicine(Panax notoginseng saponins[PNS])and a living autotrophic microorganism(microalgae Chlorella pyrenoidosa[MA])were successfully encapsulated into the scaffolds.The encapsulated PNS could be gradually released from the scaffolds,which promoted cell adhesion,proliferation,migration,and tube formation in vitro.In addition,benefiting from the photosynthetic oxygenation of the alive MA,the obtained scaffolds would produce sustainable oxygen under light illumination,exerting a protective effect against hypoxia-induced cell death.Based on these features,we have demonstrated through in vivo experiments that these living Chinese herbal scaffolds could efficiently alleviate local hypoxia,enhance angiogenesis,and thereby accelerate wound closure in diabetic mice,indicating their great potential in wound healing and other tissue repair applications.