Stem cell therapies have made great progress in the treatment of diabetic wounds during recent decades,while their short in vivo residence,alloimmune reactions,undesired behaviors,and dramatic losses of cell functions...Stem cell therapies have made great progress in the treatment of diabetic wounds during recent decades,while their short in vivo residence,alloimmune reactions,undesired behaviors,and dramatic losses of cell functions still hinder the translation of them into clinic.Here,inspired by the natural components of stem cell niches,we presented novel microfluidic hydrogel microcarriers with extracellular matrix(ECM)-like composition and adipose-derived stem cells(ADSCs)encapsulation for diabetic wound healing.As the hydrogel was synthesized by conjugating hyaluronic acid methacryloyl(HAMA)onto the Fibronectin(FN)molecule chain(FN-HAMA),the laden ADSCs in the microcarriers showed improved bioactivities and pro-regenerative capabilities.Based on these features,we have demonstrated that these ADSCs microcarriers exhibited significant promotion of neovascularization,follicular rejuvenation,and collagen deposition in a mouse diabetic wound model.These results indicated that the stem cell niche-inspired FN-HAMA microcarriers with ADSCs encapsulation have great clinical potential for diabetic wound treatment.展开更多
When organs,especially external organs are injured,pathogens and excessive water loss can threaten the wound healing process and cause local irreversible tissue damage.Here,novel natural κ-Carrageenan microparticles(...When organs,especially external organs are injured,pathogens and excessive water loss can threaten the wound healing process and cause local irreversible tissue damage.Here,novel natural κ-Carrageenan microparticles(MPs)able to deliver bioactive proteins and small molecules to the wound surface for promoted regeneration were developed using microfluidic electrospray.The side chains of κ-Carrageenan were modified with methacrylate pendant groups to make the monomer photonic cross-linkable.By changing the concentration of methacrylated-κ-Carrageenan,different porosities of MPs with controllable drug loading were achieved.The size of the MPs can also be tailored by adjusting the voltage of the applied electric field.Vascular endothelial growth factor(VEGF)and antimicrobial peptides Eumenitin were co-loaded into the microparticles(VEGF-Eumenitin-MPs)and released sustainedly in phosphate-buffered saline.The VEGF-Eumenitin-MPs had high biocompatibility and intensive antibacterial activities for bacteria.Furthermore,the antibacterial and angiogenetic properties of the VEGF-Eumenitin-MPs were demonstrated in a infectious wound model and the chronic wound healing process was significantly enhanced in vivo.Therefore,the developed porous MPs with sustained drug release properties have the potential to serve as a platform to deliver bioactive proteins and small molecules to the wound surface for promoted regeneration.展开更多
Alzheimer’s disease(AD)is a progressive neurodegenerative disease with a complex etiology.The main neu-ropathological feature is the accumulation of amyloid-beta(Aβ),and the dysregulation of the cholinergic system i...Alzheimer’s disease(AD)is a progressive neurodegenerative disease with a complex etiology.The main neu-ropathological feature is the accumulation of amyloid-beta(Aβ),and the dysregulation of the cholinergic system is well associated with its mechanism of occurrence,for which no effective treatment is yet available.Daily oral administration remains the mainstay of treatment with AD,and how to improve the efficacy,prolong adsorp-tion and medication compliance is still the focus of the current solution.We proposed a microcapsule based on microfluidic electrospray to form an intestinal epithelial lining for AD treatment,reducing the frequency of administration.Microfluidic electrospray technology was recruited to overcome the limitations associated with the variability in the microencapsulation production process and to produce functional microcapsules with finely adapted chemical composition,capsule thickness and encapsulant volume ratio.These microcapsules could slowly release drugs after adhering to the intestine,and their effectiveness and safety were further evaluated using cell culture studies and animal model studies.The results from the in vivo and in vitro experiments showed a significant reduction in administration frequency(i.e.,from daily medication to once every five days),superior therapeutic efficacy and sufficient safety of these microcapsules in cell culture and APP/PS1 mice.These features make the microcapsules an excellent drug delivery system and represent great potential for clinical applications in AD.展开更多
Wearable biosensors,which aim at providing continuous,real-time physiological information via monitoring and screening biomarkers in human body,are receiving increasing attention among various fields including dis-eas...Wearable biosensors,which aim at providing continuous,real-time physiological information via monitoring and screening biomarkers in human body,are receiving increasing attention among various fields including dis-ease treatment,diagnosis and self-health management.The ongoing development in this realm starves for the exploration of fully-integrated,non-invasive devices.In this paper,we review the latest achievements with break-through significance on the wearable biosensors.We start with the classification of different types of wearable electronic devices and analyze their characteristics and application values.Subsequently,we introduce a fully-integrated microneedle-based sensor and provide an in-depth look at its structure,subcomponents and in vivo performances.Finally,we put forward critical commentaries and clarify the direction of future researches.展开更多
Several therapeutic drugs including heptamethine cyanine dye(IR-780),doxorubicin(DOX),and others have exhibited positive outcomes in the treatment of multiple myeloma(MM).However,curing MM is still hampered by undesir...Several therapeutic drugs including heptamethine cyanine dye(IR-780),doxorubicin(DOX),and others have exhibited positive outcomes in the treatment of multiple myeloma(MM).However,curing MM is still hampered by undesired off-target effects and uncontrolled release of the therapeutics.Herein,we present novel MMmimicking nanocarriers by integration of DOX,IR-780,and MM cell membrane with zeolitic imidazolate framework-8(ZIF-8)nanoparticles(D/INPs@CM)for MM treatment.The nanocarriers were fabricated by co-loading DOX and IR-780 into ZIF-8 and further coated with the cell membrane.After intravenous injection,the D/INPs@CM can enter the bone marrow and target the tumor cells owing to bone marrow homing and homologous targeting properties of the MM cell membrane.Once accumulating in the tumor site,ZIF-8 decomposed under the acid microenvironment and released the encapsulated DOX and IR-780.As a result,D/INPs@CM showed the best MM tumor eradication performance compared to D/INPs,without displaying noticeable systemic toxicity.All these features suggest that our biomimetic nanocarriers may have great potential for the precise and targeted therapy of MM and related other hematological malignancies.展开更多
基金supported by the National Key Research and Development Program of China(2020YFA0908200)the National Natural Science Foundation of China(81974288,T2225003 and 52073060)+2 种基金the Strategic Priority Research Program of the Chinese Academy of Science(XDA16021103)the Guangdong Basic and Applied Basic Research Foundation(2021B1515120054)the Shenzhen Fundamental Research Program(JCYJ20190813152616459 and JCYJ20210324133214038).
文摘Stem cell therapies have made great progress in the treatment of diabetic wounds during recent decades,while their short in vivo residence,alloimmune reactions,undesired behaviors,and dramatic losses of cell functions still hinder the translation of them into clinic.Here,inspired by the natural components of stem cell niches,we presented novel microfluidic hydrogel microcarriers with extracellular matrix(ECM)-like composition and adipose-derived stem cells(ADSCs)encapsulation for diabetic wound healing.As the hydrogel was synthesized by conjugating hyaluronic acid methacryloyl(HAMA)onto the Fibronectin(FN)molecule chain(FN-HAMA),the laden ADSCs in the microcarriers showed improved bioactivities and pro-regenerative capabilities.Based on these features,we have demonstrated that these ADSCs microcarriers exhibited significant promotion of neovascularization,follicular rejuvenation,and collagen deposition in a mouse diabetic wound model.These results indicated that the stem cell niche-inspired FN-HAMA microcarriers with ADSCs encapsulation have great clinical potential for diabetic wound treatment.
基金supported by the National Key Research and Development Program of China(2020YFA0908200)the National Natural Science Foundation of China(52073060 and 61927805)+1 种基金the Guangdong Basic and Applied Basic Research Foundation(2019A1515011750)the Shenzhen Fundamental Research Program(JCYJ20190813152616459,JCYJ20210324133214038 and JCYJ20190808120405672).
文摘When organs,especially external organs are injured,pathogens and excessive water loss can threaten the wound healing process and cause local irreversible tissue damage.Here,novel natural κ-Carrageenan microparticles(MPs)able to deliver bioactive proteins and small molecules to the wound surface for promoted regeneration were developed using microfluidic electrospray.The side chains of κ-Carrageenan were modified with methacrylate pendant groups to make the monomer photonic cross-linkable.By changing the concentration of methacrylated-κ-Carrageenan,different porosities of MPs with controllable drug loading were achieved.The size of the MPs can also be tailored by adjusting the voltage of the applied electric field.Vascular endothelial growth factor(VEGF)and antimicrobial peptides Eumenitin were co-loaded into the microparticles(VEGF-Eumenitin-MPs)and released sustainedly in phosphate-buffered saline.The VEGF-Eumenitin-MPs had high biocompatibility and intensive antibacterial activities for bacteria.Furthermore,the antibacterial and angiogenetic properties of the VEGF-Eumenitin-MPs were demonstrated in a infectious wound model and the chronic wound healing process was significantly enhanced in vivo.Therefore,the developed porous MPs with sustained drug release properties have the potential to serve as a platform to deliver bioactive proteins and small molecules to the wound surface for promoted regeneration.
基金This work was supported partly by grants from the National Natu-ral Science Foundation of China(No.82071186)Clinical Trials from the Affiliated Drum Tower Hospital,Medical School of Nanjing Univer-sity(No.2022-LCYG-MS-05)+1 种基金National Key Research and Development Program of China(No.2022YFA1105300)Jiangsu Province Senior Health Project(No.LKZ2023014).
文摘Alzheimer’s disease(AD)is a progressive neurodegenerative disease with a complex etiology.The main neu-ropathological feature is the accumulation of amyloid-beta(Aβ),and the dysregulation of the cholinergic system is well associated with its mechanism of occurrence,for which no effective treatment is yet available.Daily oral administration remains the mainstay of treatment with AD,and how to improve the efficacy,prolong adsorp-tion and medication compliance is still the focus of the current solution.We proposed a microcapsule based on microfluidic electrospray to form an intestinal epithelial lining for AD treatment,reducing the frequency of administration.Microfluidic electrospray technology was recruited to overcome the limitations associated with the variability in the microencapsulation production process and to produce functional microcapsules with finely adapted chemical composition,capsule thickness and encapsulant volume ratio.These microcapsules could slowly release drugs after adhering to the intestine,and their effectiveness and safety were further evaluated using cell culture studies and animal model studies.The results from the in vivo and in vitro experiments showed a significant reduction in administration frequency(i.e.,from daily medication to once every five days),superior therapeutic efficacy and sufficient safety of these microcapsules in cell culture and APP/PS1 mice.These features make the microcapsules an excellent drug delivery system and represent great potential for clinical applications in AD.
基金supported by the National Natural Science Foun-dation of China(Grant 82102511)the Natural Science Foundation of Jiangsu(Grants BK20210021 and BK20210010)Research Project of Jiangsu Province Health Committee(Grant M2021031).
文摘Wearable biosensors,which aim at providing continuous,real-time physiological information via monitoring and screening biomarkers in human body,are receiving increasing attention among various fields including dis-ease treatment,diagnosis and self-health management.The ongoing development in this realm starves for the exploration of fully-integrated,non-invasive devices.In this paper,we review the latest achievements with break-through significance on the wearable biosensors.We start with the classification of different types of wearable electronic devices and analyze their characteristics and application values.Subsequently,we introduce a fully-integrated microneedle-based sensor and provide an in-depth look at its structure,subcomponents and in vivo performances.Finally,we put forward critical commentaries and clarify the direction of future researches.
基金National Key Research and Development Program of China,Grant/Award Number:2022YFA1105304National Natural Science Foundation of China,Grant/Award Numbers:32201088,82273954+1 种基金Natural Science Foundation of Jiangsu Province,Grant/Award Number:BK20210010Fundings for Clinical Trials from the Affiliated Drum Tower Hospital,Medical School of Nanjing University,Grant/Award Number:2022-LCYJ-MS-16。
文摘Several therapeutic drugs including heptamethine cyanine dye(IR-780),doxorubicin(DOX),and others have exhibited positive outcomes in the treatment of multiple myeloma(MM).However,curing MM is still hampered by undesired off-target effects and uncontrolled release of the therapeutics.Herein,we present novel MMmimicking nanocarriers by integration of DOX,IR-780,and MM cell membrane with zeolitic imidazolate framework-8(ZIF-8)nanoparticles(D/INPs@CM)for MM treatment.The nanocarriers were fabricated by co-loading DOX and IR-780 into ZIF-8 and further coated with the cell membrane.After intravenous injection,the D/INPs@CM can enter the bone marrow and target the tumor cells owing to bone marrow homing and homologous targeting properties of the MM cell membrane.Once accumulating in the tumor site,ZIF-8 decomposed under the acid microenvironment and released the encapsulated DOX and IR-780.As a result,D/INPs@CM showed the best MM tumor eradication performance compared to D/INPs,without displaying noticeable systemic toxicity.All these features suggest that our biomimetic nanocarriers may have great potential for the precise and targeted therapy of MM and related other hematological malignancies.
