Immune cells play a crucial regulatory role in inflammatory phase and proliferative phase during skin healing.How to programmatically activate sequential immune responses is the key for scarless skin regeneration.In t...Immune cells play a crucial regulatory role in inflammatory phase and proliferative phase during skin healing.How to programmatically activate sequential immune responses is the key for scarless skin regeneration.In this study,an“Inner-Outer”IL-10-loaded electrospun fiber with cascade release behavior was constructed.During the inflammatory phase,the electrospun fiber released a lower concentration of IL-10 within the wound,inhibiting excessive recruitment of inflammatory cells and polarizing macrophages into anti-inflammatory phenotype“M2c”to suppress excessive inflammation response.During the proliferative phase,a higher concentration of IL-10 released by the fiber and the anti-fibrotic cytokines secreted by polarized“M2c”directly acted on dermal fibroblasts to simultaneously inhibit extracellular matrix overdeposition and promote fibroblast migration.The“Inner-Outer”IL-10-loaded electrospun fiber programmatically activated the sequential immune responses during wound healing and led to scarless skin regeneration,which is a promising immunomodulatory biomaterial with great potential for promoting complete tissue regeneration.展开更多
Tuberculosis(TB),caused by Mycobacterium tuberculosis,continues to pose a significant threat to global health.The resilience of TB is amplified by a myriad of physical,biological,and biopharmaceutical barriers that ch...Tuberculosis(TB),caused by Mycobacterium tuberculosis,continues to pose a significant threat to global health.The resilience of TB is amplified by a myriad of physical,biological,and biopharmaceutical barriers that challenge conventional therapeutic approaches.This review navigates the intricate landscape of TB treatment,from the stealth of latent infections and the strength of granuloma formations to the daunting specters of drug resistance and altered gene expression.Amidst these challenges,traditional therapies often fail,contending with inconsistent bioavailability,prolonged treatment regimens,and socioeconomic burdens.Nanoscale Drug Delivery Systems(NDDSs)emerge as a promising beacon,ready to overcome these barriers,offering better drug targeting and improved patient adherence.Through a critical approach,we evaluate a spectrum of nanosystems and their efficacy against MTB both in vitro and in vivo.This review advocates for the intensification of research in NDDSs,heralding their potential to reshape the contours of global TB treatment strategies.展开更多
Hydrogel microspheres,with their high water content and tunable physicochemical properties,have emerged as a promising class of materials for a myriad of biomedical applications.1 These microscale particles,which can ...Hydrogel microspheres,with their high water content and tunable physicochemical properties,have emerged as a promising class of materials for a myriad of biomedical applications.1 These microscale particles,which can be fabricated from both natural and synthetic polymers,exhibit diverse properties and bear a striking resemblance to the native extracellular matrix.2 This makes them highly suitable as substrates for cell culture,templates for tissue engineering,and vehicles for drug and protein delivery.展开更多
Remarkable progress in phototherapy has been made in recent decades,due to its non-invasiveness and instant therapeutic efficacy.In addition,with the rapid development of nanoscience and nanotechnology,phototherapy sy...Remarkable progress in phototherapy has been made in recent decades,due to its non-invasiveness and instant therapeutic efficacy.In addition,with the rapid development of nanoscience and nanotechnology,phototherapy systems based on nanoparticles or nanocomposites also evolved as an emerging hotspot in nanomedicine research,especially in cancer.In this review,first we briefly introduce the history of phototherapy,and the mechanisms of phototherapy in cancer treatment.Then,we summarize the representative development over the past three to five years in nanoparticle-based phototherapy and highlight the design of the innovative nanoparticles thereof.Finally,we discuss the feasibility and the potential of the nanoparticle-based phototherapy systems in clinical anticancer therapeutic applications,aiming to predict future research directions in this field.Our review is a tutorial work,aiming at providing useful insights to researchers in the field of nanotechnology,nanoscience and cancer.展开更多
Oral insulin delivery could change the life of millions of diabetic patients as an effective,safe,easy-to-use,and affordable alternative to insulin injections,known by an inherently thwarted patient compliance.Here,we...Oral insulin delivery could change the life of millions of diabetic patients as an effective,safe,easy-to-use,and affordable alternative to insulin injections,known by an inherently thwarted patient compliance.Here,we designed a multistage nanoparticle(NP)system capable of circumventing the biological barriers that lead to poor drug absorption and bioavailability after oral administration.The nanosystem consists of an insulin-loaded porous silicon NP encapsulated into a pH-responsive lignin matrix,and surface-functionalized with the Fc fragment of immunoglobulin G,which acts as a targeting ligand for the neonatal Fc receptor(FcRn).The developed NPs presented small size(211±1 nm)and narrow size distribution.The NPs remained intact in stomach and intestinal pH conditions,releasing the drug exclusively at pH 7.4,which mimics blood circulation.This formulation showed to be highly cytocompatible,and surface plasmon resonance studies demonstrated that FcRn-targeted NPs present higher capacity to interact and being internalized by the Caco-2 cells,which express FcRn,as demonstrated by Western blot.Ultimately,in vitro permeability studies showed that Fc-functionalized NPs induced an increase in the amount of insulin that permeated across a Caco-2/HT29-MTX co-culture model,showing apparent permeability coefficients(Papp)of 2.37×106 cm/s,over the 1.66×106 cm/s observed for their non-functionalized counterparts.Overall,these results demonstrate the potential of these NPs for oral delivery of anti-diabetic drugs.展开更多
Thrombosis and infections are the two major complications associated with extracorporeal circuits and indwelling medical devices,leading to significant mortality in clinic.To address this issue,here,we report a biomim...Thrombosis and infections are the two major complications associated with extracorporeal circuits and indwelling medical devices,leading to significant mortality in clinic.To address this issue,here,we report a biomimetic surface engineering strategy by the integration of mussel-inspired adhesive peptide,with bio-orthogonal click chemistry,to tailor the surface functionalities of tubing and catheters.Inspired by mussel adhesive foot protein,a bioclickable peptide mimic(DOPA)4-azidebased structure is designed and grafted on an aminated tubing robustly based on catechol-amine chemistry.Then,the dibenzylcyclooctyne(DBCO)modified nitric oxide generating species of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid(DOTA)chelated copper ions and the DBCO-modified antimicrobial peptide(DBCO-AMP)are clicked onto the grafted surfaces via bio-orthogonal reaction.The combination of the robustly grafted AMP and Cu-DOTA endows the modified tubing with durable antimicrobial properties and ability in long-term catalytically generating NO from endogenous snitrosothiols to resist adhesion/activation of platelets,thus preventing the formation of thrombosis.Overall,this biomimetic surface engineering technology provides a promising solution for multicomponent surface functionalization and the surface bioengineering of biomedical devices with enhanced clinical performance.展开更多
Antioxidant collagen hydrolysates refers to the peptides mixture with antioxidant properties identified from hydrolyzed collagen.Due to its specific structural,biological and physicochemical properties,collagen hydrol...Antioxidant collagen hydrolysates refers to the peptides mixture with antioxidant properties identified from hydrolyzed collagen.Due to its specific structural,biological and physicochemical properties,collagen hydrolysates have been explored as a multifunctional antioxidant in the biomedical field.In this review,we summarize recent advances in antioxidant collagen hydrolysates development.Initially,the preparation process of antioxidant collagen hydrolysates is introduced,including the production and separation methods.Then the effects and the mechanisms of amino acid composition and collagen peptide structure on the antioxidant activity of collagen hydrolysates are reviewed.Finally,the applications of antioxidant collagen hydrolysates in biomedical domains are summarized,with critical discussions about the advantages,current limitations and challenges to be resolved in the future.展开更多
Background:Transcriptomic and proteomic profiling of human brain tissue is hindered by the availability of fresh samples from living patients.Postmortem samples usually represent the advanced disease stage of the pati...Background:Transcriptomic and proteomic profiling of human brain tissue is hindered by the availability of fresh samples from living patients.Postmortem samples usually represent the advanced disease stage of the patient.Fur-thermore,the postmortem interval can affect the transcriptomic and proteomic profiles.Therefore,fresh brain tissue samples from living patients represent a valuable resource of metabolically intact tissue.Implantation of deep brain stimulation(DBS)electrodes into the human brain is a neurosurgical treatment for,e.g.,movement disorders.Here,we describe an improved approach to collecting brain tissues from surgical instruments used in implantation of DBS device for transcriptomics and proteomics analyses.Methods:Samples were extracted from guide tubes and recording electrodes used in routine DBS implantation procedure to treat patients with Parkinson’s disease,genetic dystonia and tremor.RNA sequencing was performed in tissues extracted from the recording microelectrodes and liquid chromatography-mass spectrometry(LC-MS)per-formed in tissues from guide tubes.To assess the performance of the current approach,the obtained datasets were compared with previously published datasets representing brain tissues.Results:Altogether,32,034 RNA transcripts representing the unique Ensembl gene identifiers were detected from eight samples representing both hemispheres of four patients.By using LC-MS,we identified 734 unique proteins from 31 samples collected from 14 patients.The datasets are available in the BioStudies database(accession number S-BSST667).Our results indicate that surgical instruments used in DBS installation retain brain material sufficient for protein and gene expression studies.Comparison with previously published datasets obtained with similar approach proved the robustness and reproducibility of the protocol.Conclusions:The instruments used during routine DBS surgery are a useful source for obtaining fresh brain tis-sues from living patients.This approach overcomes the issues that arise from using postmortem tissues,such as the effect of postmortem interval on transcriptomic and proteomic landscape of the brain,and can be used for studying molecular aspects of DBS-treatable diseases.展开更多
基金This work was supported by the National Key Research and Development Program of China(2020YFA0908200)National Natural Science Foundation of China(81701907 and 81871472)+7 种基金The in vitro biological experiment was supported by National Natural Science Foundation of China(81772099 and 81801928)Shanghai Sailing Program(18YF1412400)The production and detection of the scaffold were supported by Shanghai Jiao Tong University“Medical and Research”Program(ZH2018ZDA04)Science and Technology Commission of Shanghai Municipality(19440760400)The in vivo biological experiment were supported Pujiang program of SSTC(18PJ1407100)Prof.H.Zhang acknowledges the financial support from Academy of Finland(328933)Sigrid Juselius Foundation(28001830K1)Prof.H.A.Santos acknowledges the financial support from HiLIFE Research Funds and Sigrid Juselius Foundation.
文摘Immune cells play a crucial regulatory role in inflammatory phase and proliferative phase during skin healing.How to programmatically activate sequential immune responses is the key for scarless skin regeneration.In this study,an“Inner-Outer”IL-10-loaded electrospun fiber with cascade release behavior was constructed.During the inflammatory phase,the electrospun fiber released a lower concentration of IL-10 within the wound,inhibiting excessive recruitment of inflammatory cells and polarizing macrophages into anti-inflammatory phenotype“M2c”to suppress excessive inflammation response.During the proliferative phase,a higher concentration of IL-10 released by the fiber and the anti-fibrotic cytokines secreted by polarized“M2c”directly acted on dermal fibroblasts to simultaneously inhibit extracellular matrix overdeposition and promote fibroblast migration.The“Inner-Outer”IL-10-loaded electrospun fiber programmatically activated the sequential immune responses during wound healing and led to scarless skin regeneration,which is a promising immunomodulatory biomaterial with great potential for promoting complete tissue regeneration.
基金support from the S˜ao Paulo Research Foundation(FAPESP,Brazil),Grant numbers#01664-1,#2022/02661-3 and#2020/16573-3,respectivelyNational Council for Scientific and Technological Development(CNPq):Productivity Research Fellows(PQ CNPq):305408/2022-4This study is part of the National Institute of Science and Technology in Pharmaceutical Nanotechnology:a transdisciplinary approach,INCT-NANOFARMA,which is supported by S˜ao Paulo Research Foundation(FAPESP,Brazil)Grant#2014/50928-2,and by“Conselho Nacional de Desenvolvimento Científico e Tecnol′ogico”(CNPq,Brazil)Grant#465687/2014-8.Prof.H.A.Santos acknowledges financial support from the Research Council of Finland(Grant No.331151)and the UMCG Research Funds.
文摘Tuberculosis(TB),caused by Mycobacterium tuberculosis,continues to pose a significant threat to global health.The resilience of TB is amplified by a myriad of physical,biological,and biopharmaceutical barriers that challenge conventional therapeutic approaches.This review navigates the intricate landscape of TB treatment,from the stealth of latent infections and the strength of granuloma formations to the daunting specters of drug resistance and altered gene expression.Amidst these challenges,traditional therapies often fail,contending with inconsistent bioavailability,prolonged treatment regimens,and socioeconomic burdens.Nanoscale Drug Delivery Systems(NDDSs)emerge as a promising beacon,ready to overcome these barriers,offering better drug targeting and improved patient adherence.Through a critical approach,we evaluate a spectrum of nanosystems and their efficacy against MTB both in vitro and in vivo.This review advocates for the intensification of research in NDDSs,heralding their potential to reshape the contours of global TB treatment strategies.
文摘Hydrogel microspheres,with their high water content and tunable physicochemical properties,have emerged as a promising class of materials for a myriad of biomedical applications.1 These microscale particles,which can be fabricated from both natural and synthetic polymers,exhibit diverse properties and bear a striking resemblance to the native extracellular matrix.2 This makes them highly suitable as substrates for cell culture,templates for tissue engineering,and vehicles for drug and protein delivery.
基金The Academy of Finland(Grants Nos.331151 and 331106),the Sigrid Jus´elius Foundation,the China Scholarship Council,and the UMCG Research Funds are acknowledged for financial support.
文摘Remarkable progress in phototherapy has been made in recent decades,due to its non-invasiveness and instant therapeutic efficacy.In addition,with the rapid development of nanoscience and nanotechnology,phototherapy systems based on nanoparticles or nanocomposites also evolved as an emerging hotspot in nanomedicine research,especially in cancer.In this review,first we briefly introduce the history of phototherapy,and the mechanisms of phototherapy in cancer treatment.Then,we summarize the representative development over the past three to five years in nanoparticle-based phototherapy and highlight the design of the innovative nanoparticles thereof.Finally,we discuss the feasibility and the potential of the nanoparticle-based phototherapy systems in clinical anticancer therapeutic applications,aiming to predict future research directions in this field.Our review is a tutorial work,aiming at providing useful insights to researchers in the field of nanotechnology,nanoscience and cancer.
基金Dr.Shiqi Wang acknowledges financial support from Academy of Finland(decision no.331106)Prof.H´elder A.Santos acknowledges financial support from the HiLIFE Research Funds,the Sigrid Jus´elius Foundation(decision no.4704580)+1 种基金the Academy of Finland(grant no.317042 and 331151)The authors acknowledge the following core facilities funded by Biocenter Finland:Electron Microscopy Unity of the University of Helsinki,Finland for providing the facilities for TEM imaging.The authors acknowledge the use of ALD center Finland research infrastructure for EDX measurements.The authors acknowledge Tomas Bauleth-Ramos for technical support with the cell viability assays.
文摘Oral insulin delivery could change the life of millions of diabetic patients as an effective,safe,easy-to-use,and affordable alternative to insulin injections,known by an inherently thwarted patient compliance.Here,we designed a multistage nanoparticle(NP)system capable of circumventing the biological barriers that lead to poor drug absorption and bioavailability after oral administration.The nanosystem consists of an insulin-loaded porous silicon NP encapsulated into a pH-responsive lignin matrix,and surface-functionalized with the Fc fragment of immunoglobulin G,which acts as a targeting ligand for the neonatal Fc receptor(FcRn).The developed NPs presented small size(211±1 nm)and narrow size distribution.The NPs remained intact in stomach and intestinal pH conditions,releasing the drug exclusively at pH 7.4,which mimics blood circulation.This formulation showed to be highly cytocompatible,and surface plasmon resonance studies demonstrated that FcRn-targeted NPs present higher capacity to interact and being internalized by the Caco-2 cells,which express FcRn,as demonstrated by Western blot.Ultimately,in vitro permeability studies showed that Fc-functionalized NPs induced an increase in the amount of insulin that permeated across a Caco-2/HT29-MTX co-culture model,showing apparent permeability coefficients(Papp)of 2.37×106 cm/s,over the 1.66×106 cm/s observed for their non-functionalized counterparts.Overall,these results demonstrate the potential of these NPs for oral delivery of anti-diabetic drugs.
基金the National Natural Science Foundation of China(Project 82072072)(Z.Y)International Cooperation Project by Science and Technology Department of Sichuan Province(2021YFH0056 and 2019YFH0103)(Z.Y)the Fundamental Research Funds for the Central Universities(2682020ZT82 and 2682020ZT76)(Z.Y).
文摘Thrombosis and infections are the two major complications associated with extracorporeal circuits and indwelling medical devices,leading to significant mortality in clinic.To address this issue,here,we report a biomimetic surface engineering strategy by the integration of mussel-inspired adhesive peptide,with bio-orthogonal click chemistry,to tailor the surface functionalities of tubing and catheters.Inspired by mussel adhesive foot protein,a bioclickable peptide mimic(DOPA)4-azidebased structure is designed and grafted on an aminated tubing robustly based on catechol-amine chemistry.Then,the dibenzylcyclooctyne(DBCO)modified nitric oxide generating species of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid(DOTA)chelated copper ions and the DBCO-modified antimicrobial peptide(DBCO-AMP)are clicked onto the grafted surfaces via bio-orthogonal reaction.The combination of the robustly grafted AMP and Cu-DOTA endows the modified tubing with durable antimicrobial properties and ability in long-term catalytically generating NO from endogenous snitrosothiols to resist adhesion/activation of platelets,thus preventing the formation of thrombosis.Overall,this biomimetic surface engineering technology provides a promising solution for multicomponent surface functionalization and the surface bioengineering of biomedical devices with enhanced clinical performance.
基金supported by grants from the National Natural Science Foundation of China(No.52242208).
文摘Antioxidant collagen hydrolysates refers to the peptides mixture with antioxidant properties identified from hydrolyzed collagen.Due to its specific structural,biological and physicochemical properties,collagen hydrolysates have been explored as a multifunctional antioxidant in the biomedical field.In this review,we summarize recent advances in antioxidant collagen hydrolysates development.Initially,the preparation process of antioxidant collagen hydrolysates is introduced,including the production and separation methods.Then the effects and the mechanisms of amino acid composition and collagen peptide structure on the antioxidant activity of collagen hydrolysates are reviewed.Finally,the applications of antioxidant collagen hydrolysates in biomedical domains are summarized,with critical discussions about the advantages,current limitations and challenges to be resolved in the future.
基金the Academy of Finland(Decision Numbers#311934 R.H.[profiling programme]and#331436 J.U.),Pediatric Research Foundation,Finland(J.U.and R.H.),Biocenter Oulu(J.U.and R.H.),Biocenter Finland,Special State Grants for Health Research,Oulu University Hospital,Finland(J.U.)the Terttu Foundation,Oulu University Hospital,Finland(J.K.).
文摘Background:Transcriptomic and proteomic profiling of human brain tissue is hindered by the availability of fresh samples from living patients.Postmortem samples usually represent the advanced disease stage of the patient.Fur-thermore,the postmortem interval can affect the transcriptomic and proteomic profiles.Therefore,fresh brain tissue samples from living patients represent a valuable resource of metabolically intact tissue.Implantation of deep brain stimulation(DBS)electrodes into the human brain is a neurosurgical treatment for,e.g.,movement disorders.Here,we describe an improved approach to collecting brain tissues from surgical instruments used in implantation of DBS device for transcriptomics and proteomics analyses.Methods:Samples were extracted from guide tubes and recording electrodes used in routine DBS implantation procedure to treat patients with Parkinson’s disease,genetic dystonia and tremor.RNA sequencing was performed in tissues extracted from the recording microelectrodes and liquid chromatography-mass spectrometry(LC-MS)per-formed in tissues from guide tubes.To assess the performance of the current approach,the obtained datasets were compared with previously published datasets representing brain tissues.Results:Altogether,32,034 RNA transcripts representing the unique Ensembl gene identifiers were detected from eight samples representing both hemispheres of four patients.By using LC-MS,we identified 734 unique proteins from 31 samples collected from 14 patients.The datasets are available in the BioStudies database(accession number S-BSST667).Our results indicate that surgical instruments used in DBS installation retain brain material sufficient for protein and gene expression studies.Comparison with previously published datasets obtained with similar approach proved the robustness and reproducibility of the protocol.Conclusions:The instruments used during routine DBS surgery are a useful source for obtaining fresh brain tis-sues from living patients.This approach overcomes the issues that arise from using postmortem tissues,such as the effect of postmortem interval on transcriptomic and proteomic landscape of the brain,and can be used for studying molecular aspects of DBS-treatable diseases.
