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Enzymatic co-crosslinking of star-shaped poly(ethylene glycol)tyramine and hyaluronic acid tyramine conjugates provides elastic biocompatible and biodegradable hydrogels

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Bioactive Materials 2023年第2期20卷 53-63页

作者： Rong Wang Xiaobin Huang Bram Zoetebier Pieter JDijkstra Marcel Karperien Department of Developmental BioEngineering Faculty of Science and TechnologyTech Med CentreUniversity of TwenteP.O.Box 2177500 AEEnschedethe Netherlands radboudumc Dept.of Dentistry-Regenerative BiomaterialsRadboud University Medical CenterPhilips van Leydenlaan 256525 EX NijmegenThe Netherlands Department of Oral and Maxillofacial Surgery School of Dental MedicineUniversity of Pennsylvania240 South 40th StreetPhiladelphiaPA 19104-6030US

A combination of the viscoelastic properties of hyaluronic acid(HA)and the elastic properties of star shaped 8-arm poly(ethylene glycol)(8-arm PEG)was used to design in-situ forming *** were prepared by the enzymatic crosslinking of a partially tyramine modified 8-arm PEG and a tyramine conjugated HA using horseradish peroxidase in the presence of hydrogen *** of the homopolymer conjugates and mixtures thereof were rapidly formed within seconds under physiological conditions at low polymer and enzyme *** hydrogels with high gel content(≥95%)and high storage moduli(up to 22.4 kPa)were *** in vitro study in the presence of hyaluronidase(100 U/mL)revealed that with increasing PEG content the degradation time of the hybrid hydrogels increased up to several weeks,whereas hydrogels composed of only hyaluronic acid degraded within 2 *** mesenchymal stem cells(hMSCs)incorporated in the hybrid hydrogels remained viable as shown by a PrestoBlue and a live-dead assay,confirming the biocompatibility of the *** production of an extracellular matrix by re-differentiation of encapsulated human chondrocytes was followed over a period of 28 *** expression indicated that these highly elastic hydrogels induced an enhanced production of collagen type *** low PEG-TA/HA-TA ratios a higher expression of SOX 9 and ACAN was *** results indicate that by modulating the ratio of PEG/HA,injectable hydrogels can be prepared applicable as scaffolds for tissue regeneration applications.

关键词： PEG-OH8 HA Enzymatic crosslinking hydrogel Degradation Proliferation&differentiation

Gene expression profiles of human adipose-derived mesenchymal stem cells dynamically seeded on clinically available processed nerve allografts and collagen nerve guides

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Neural Regeneration Research 2021年第8期16卷 1613-1621页

作者： Femke Mathot Nadia Rbia Roman Thaler Allan B.Dietz Andre Jvan Wijnen Allen T.Bishop Alexander Y.Shin Department of Orthopedic Surgery Mayo ClinicRochesterMNUSA Department of Plastic Surgery RadboudumcNijmegenThe Netherlands Department of Dermatology Erasmus Medical CenterRotterdamThe Netherlands Department of Biochemistry and Molecular Biology Mayo ClinicRochesterMNUSA Department of Laboratory Medicine and Pathology Mayo ClinicRochesterMNUSA

It was hypothesized that mesenchymal stem cells(MSCs) could provide necessary trophic factors when seeded onto the surfaces of commonly used nerve graft substitutes. We aimed to determine the gene expression of MSCs when influenced by Avance■ Nerve Grafts or Neura Gen■ Nerve Guides. Human adipose-derived MSCs were cultured and dynamically seeded onto 30 Avance■ Nerve Grafts and 30 Neura Gen■ Nerve Guides for 12 hours. At six time points after seeding, quantitative polymerase chain reaction analyses were performed for five samples per group. Neurotrophic [nerve growth factor(NGF), glial cell line-derived neurotrophic factor(GDNF), pleiotrophin(PTN), growth associated protein 43(GAP43) and brain-derived neurotrophic factor(BDNF)], myelination [peripheral myelin protein 22(PMP22) and myelin protein zero(MPZ)], angiogenic [platelet endothelial cell adhesion molecule 1(PECAM1/CD31) and vascular endothelial cell growth factor alpha(VEGFA)], extracellular matrix(ECM) [collagen type alpha I(COL1A1), collagen type alpha III(COL3A1), Fibulin 1(FBLN1) and laminin subunit beta 2(LAMB2)] and cell surface marker cluster of differentiation 96(CD96) gene expression was quantified. Unseeded Avance■ Nerve Grafts and Neura Gen■ Nerve Guides were used to evaluate the baseline gene expression, and unseeded MSCs provided the baseline gene expression of MSCs. The interaction of MSCs with the Avance■ Nerve Grafts led to a short-term upregulation of neurotrophic(NGF, GDNF and BDNF), myelination(PMP22 and MPZ) and angiogenic genes(CD31 and VEGFA) and a long-term upregulation of BDNF, VEGFA and COL1A1. The interaction between MSCs and the Neura Gen■ Nerve Guide led to short term upregulation of neurotrophic(NGF, GDNF and BDNF) myelination(PMP22 and MPZ), angiogenic(CD31 and VEGFA), ECM(COL1A1) and cell surface(CD96) genes and long-term upregulation of neurotrophic(GDNF and BDNF), angiogenic(CD31 and VEGFA), ECM genes(COL1A1, COL3A1, and FBLN1) and cell surface(CD96) genes. Analysis demonstrat

关键词： Avance■Nerve Grafts dynamic seeding mesenchymal stem cell NeuraGen■Nerve Guides peripheral nerve repair qPCR

Bone regeneration using coculture of mesenchymal stem cells and angiogenic cells

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Frontiers of Materials Science 2014年第1期8卷 32-38页

作者： Jin-Ling MA Jeroen J. J. P. van den BEUCKEN Ju-Li PAN Fu-Zhai CUI Su CHEN Department of VIP Service Beijing Stomatological Hospital Capital Medical University Beijing 100050 China Department of Biomaterials Radboudumc Nijmegen the Netherlands Department of Oral and Maxillofacial Surgery Beijing Stomatological Hospital Capital Medical University Beijing 100050 China State Key Laboratory of New Ceramics and Fine Processing School of Materials Science and Engineering Tsinghua University Beijing 100084 China

Cellular strategies remain a crucial component in bone tissue engineering （BTE）. So far, the outcome of cell-based strategies from initial clinical trials is far behind compared to animal studies, which is suggested to be related to insufficient nutrient and oxygen supply inside the Ussue-engineered constructs. Cocultures, by introducing angiogenic cells into osteogenic cell cultures, might provide a solution for improving vascularization and hence increasing bone formation for cell-based constructs. So far, pre-clinical studies demonstrated that cocultures enhance vascularization and bone formation compared to monocultures. However, there has been no report on the application of cocultures in clinics. Therefore, this mini-review aims to provide an overview regarding （i） critical parameters in cocultures and the outcomes of cocultures compared to monocultures in the currently available pre-clinical studies using human mesenchymal stem cells implanted in orthotopic animal models; and （ii） the usage of monocultures in clinical application in BTE.

关键词： mesenchymal stem cell (MSC) endothelial cell (EC) coculture vasculari-zation tissue regeneration

Thiol-ene conjugation of a VEGF peptide to electrospun scaffolds for potential applications in angiogenesis

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Bioactive Materials 2023年第2期20卷 306-317页

作者： Tianyu Yao Honglin Chen Rong Wang Rebeca Rivero Fengyu Wang Lilian Kessels Stijn M.Agten Tilman M.Hackeng Tim G.A.M.Wolfs Daidi Fan Matthew B.Baker Lorenzo Moroni Shaanxi Key Laboratory of Degradable Biomedical Materials and Shaanxi R&D Center of Biomaterials and Fermentation Engineering School of Chemical EngineeringNorthwest UniversityTaibai North Road 229Xi’anShaanxi710069China Complex Tissue Regeneration Department MERLN Institute for Technology Inspired Regenerative MedicineMaastricht UniversityMaastricht6229 ERthe Netherlands Guangdong Provincial People’s Hospital Guangdong Academy of Medical SciencesGuangzhou510080China radboudumc Department of Dentistry-Regenerative BiomaterialsRadboud University Medical CenterPhilips van Leydenlaan 256525 EXNijmegenthe Netherlands School of Medicine South China University of TechnologyGuangzhou510006China Maastricht University Medical Center MUMC+ P.Debyelaan 256229 HXMaastrichtthe Netherlands Research School for Cardiovascular Diseases(CARIM) Maastricht UniversityUniversiteitssingel 506229ER Maastrichtthe Netherlands School for Oncology and Developmental Biology(GROW) Maastricht UniversityUniversiteitssingel 406229ER Maastrichtthe Netherlands

Vascular endothelial growth factor(VEGF)plays a vital role in promoting attachment and proliferation of endothelial cells,and induces *** recent years,much research has been conducted on the functionalization of tissue engineering scaffolds with VEGF or a VEGF-mimetic peptide to promote ***,most chemical reactions are nonspecific and require organic solvents,which can compromise control over functionalization and alter peptide/protein *** attractive alternative is the fabrication of functionalizable electrospun fibers,which can overcome these *** this study,we used thiol-ene chemistry for the conjugation of a VEGF-mimetic peptide to the surface of poly(ε-caprolactone)(PCL)fibrous scaffolds with varying amounts of a functional PCL-diacrylate(PCL-DA)polymer.30%PCL-DA was selected due to homogeneous fiber morphology.A VEGF-mimetic peptide was then immobilized on PCL-DA fibrous scaffolds by a light-initiated thiol-ene reaction.7-Mercapto-4-methylcoumarin,RGD-FITC peptide and VEGF-TAMRA mimetic peptide were used to validate the thiol-ene reaction on the fibrous *** strength and elastic modulus of the 30%PCL-DA fibrous scaffolds were significantly increased after the *** of the 30%PCL-DA fibrous scaffolds with the VEGF peptide increased the surface water wettability of the *** structures could be obtained after using a photomask on the fibrous ***,in vitro studies indicated that scaffolds functionalized with the VEGF-mimetic peptide were able to induce phosphorylation of the VEGF receptor and enhanced HUVECs survival,proliferation and adhesion.A chick chorioallantoic membrane(CAM)assay further indicated that the VEGF peptide functionalized scaffolds were able to promote angiogenesis in *** results show that scaffold functionalization can be controlled via a simple polymer mixing approach,and that the functionalized VEGF peptide-scaffolds have potential for vascular

关键词： Electrospinning Fibrous scaffolds Thiol-ene reaction VEGF peptide

Fungi between extremotolerance and opportunistic pathogenicity on humans

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Fungal Diversity 2018年第6期93卷 195-213页

作者： Cene Gostincar Janja Zajc Metka Lenassi Ana Plemenitas Sybren de Hoog Abdullah M.S.Al-Hatmi Nina Gunde-Cimerman Department of Biology Biotechnical FacultyUniversity of LjubljanaJamnikarjeva 1011000 LjubljanaSlovenia Department of Molecular and Biomedical Sciences Jozˇef Stefan InstituteJamova 391000 LjubljanaSlovenia National Institute of Biology Vecˇna pot 1111000 LjubljanaSlovenia Institute of Biochemistry Faculty of MedicineUniversity of LjubljanaVrazov trg 21000 LjubljanaSlovenia Westerdijk Fungal Biodiversity Institute UtrechtThe Netherlands Center of Expertise in Mycology of radboudumc/Canisius Wilhelmina Ziekenhuis NijmegenThe Netherlands Directorate General of Health Services IbriOman

Numerous agents of infections in humans and other mammals are found among fungi that are able to survive extreme environmental conditions and to quickly adapt to novel ***,the relationship between opportunistic potential and polyextremotolerance was not yet studied systematically in ***,the link between polyextremotolerance and opportunistic pathogenicity is shown in a kingdom-wide phylogenetic analysis as a statistically significant co-occurrence of extremotolerance(*** and psychrotolerance)and opportunism at the level of fungal *** addition to extremotolerance,fungal opportunists share another characteristic—an apparent lack of specialised virulence *** is illustrated by a comparative genomic analysis of 20 dothideomycetous and eurotiomycetous black *** the genomes of specialised fungal plant pathogens were significantly enriched in known virulence-associated genes that encode secreted proteases,carbohydrate active enzyme families,polyketide synthases,and non-ribosomal peptide synthetases,no such signatures were observed in human *** the presented results have several *** infection of human hosts is a side effect of fungal stress tolerance and adaptability,the human body is most likely neither the preferred habitat of such species,nor important for their evolutionary *** defines opportunism as opposed to pathogenicity,where infection is advantageous for the species’*** opportunists are generally incapable of the host-to-host transmission,any host-specific adaptations are likely to be lost with the resolution of the infection,explaining the observed lack of specialised virulence *** this scenario opportunistic infections should be seen as an evolutionary dead end and unlikely to lead to true pathogenicity.

关键词： Virulence factor Extremotolerance Stress tolerance Mycosis Opportunistic infection Black yeast

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World Journal of Hepatology 2021年第11期13卷 1642-1652页

作者： Romée JALM Snijders Piotr Milkiewicz Christoph Schramm Tom JG Gevers Department of Gastroenterology and Hepatology RadboudumcNijmegen 6525GAThe Netherlands European Reference Network RARE-LIVER HamburgGermany Liver and Internal Medicine Unit Medical University of WarsawWarsaw 02-091Poland Translational Medicine Group Pomeranian Medical UniversitySzczecin 70-204Poland First Department of Medicine University Medical Center Hamburg EppendorfHamburg 20246Germany Martin Zeitz Center for Rare Diseases and Hamburg Center for Translational Immunology(HCTI) University Medical Center Hamburg EppendorfHamburg 20246Germany Division of Gastroenterology and Hepatology Maastricht University Medical CenterMaastricht 6229HXThe Netherlands

Autoimmune hepatitis(AIH)is a severe chronic autoimmune disease and has a significant impact on the patient’s quality of life,in particular regarding psychological problems such as anxiety and *** evidence on which patient-related,disease-related or physician-related factors cause health-related quality of life(HRQoL)impairment in patients with AIH is *** studies on HRQoL in AIH are mainly single-centered,comprising small numbers of patients,and difficult to compare because of the use of different questionnaires,patient populations,and cutoff *** in the pediatric field is sparse,but suggests that children/adolescents with AIH have a lower *** of HRQoL and cohesive factors in AIH are important to improve healthcare for AIH patients,for example by developing an AIH-specific chronic healthcare *** recognizing the importance of quality of life beyond the concept of biochemical and histological remission,clinicians allow us to seek enhancements and possible interventions in the management of AIH,aiming at improved health.

关键词： Autoimmune hepatitis Quality of life Depression Anxiety Corticosteroids

Intraneuronal tau aggregation induces the integrated stress response in astrocytes

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Journal of Molecular Cell Biology 2022年第10期14卷 50-68页

作者： Kevin L.Batenburg Nael N.Kasri Vivi M.Heine Wiep Scheper Department of Functional Genomics Center for Neurogenomics and Cognitive ResearchAmsterdam NeuroscienceVrĳe Universiteit AmsterdamDe Boelelaan 10851081 HV AmsterdamThe Netherlands Department of Human Genetics and Cognitive Neuroscience Donders Institute for BrainCognition and BehaviourRadboudumcGeert Grooteplein 10 Noord6500 HB NĳmegenThe Netherlands Department of Child and Adolescent Psychiatry Amsterdam UMC location Vrĳe UniversiteitAmsterdam NeuroscienceVrĳe Universiteit AmsterdamDe Boelelaan 10851081 HV AmsterdamThe Netherlands Department of Complex Trait Genetics Center for Neurogenomics and Cognitive ResearchAmsterdam NeuroscienceVrĳe Universiteit AmsterdamDe Boelelaan 10851081 HV AmsterdamThe Netherlands Department of Human Genetics Amsterdam UMC location Vrĳe UniversiteitDe Boelelaan 10851081 HV AmsterdamThe Netherlands

Progressive aggregation of tau protein in neurons is associated with neurodegeneration in *** non-autonomous disease mechanisms in astrocytes may be important drivers of the disease process but remain largely ***,we studied cell type-specific responses to intraneuronal tau aggregation prior to *** this end,we developed a fully human co-culture model of seed-independent intraneuronal tau pathology,which shows no neuron and synapse *** high-content microscopy,we show that intraneuronal tau aggregation induces oxidative stress accompanied by activation of the integrated stress response specifically in *** requires the direct co-culture with neurons and is not related to neurodegeneration or extracellular tau ***-directed antisense therapy reduced intraneuronal tau levels and aggregation and prevented the cell non-autonomous responses in *** data identify the astrocytic integrated stress response as a novel disease mechanism activated by intraneuronal tau *** addition,our data provide the first evidence for the efficacy of tau-directed antisense therapy to target cell autonomous and cell non-autonomous disease pathways in a fully human model of tau pathology.

关键词： tau aggregation astrocytes hiPSC-derived neurons integrated stress response oxidative stress antisense oligonucleotides

Phylogeny,ecology and taxonomy of systemic pathogens and their relatives in Ajellomycetaceae(Onygenales):Blastomyces,Emergomyces,Emmonsia,Emmonsiellopsis

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Fungal Diversity 2018年第3期90卷 245-291页

作者： Yanping Jiang Karolina Dukik Jose F.Munoz Lynne Sigler Ilan S.Schwartz Nelesh P.Govender Chris Kenyon Peiying Feng Bert Gerrits van den Ende J.Benjamin Stielow Alberto M.Stchigel Hongguang Lu Sybren de Hoog Department of Dermatology The Affiliated HospitalGuizhou Medical UniversityGuiyangChina Westerdijk Fungal Biodiversity Institute UtrechtThe Netherlands Center of Expertise in Mycology of radboudumc/Canisius Wilhelmina Hospital NijmegenThe Netherlands Institute of Biodiversity and Ecosystem Dynamics University of AmsterdamAmsterdamThe Netherlands Broad Institute of MIT and Harvard CambridgeMAUSA and Biological Sciences EdmontonABCanada Division of Infectious Diseases Department of MedicineFaculty of Medicine and DentistryUniversity of AlbertaEdmontonABCanada Global Health Institute Faculty of Medicine and Health SciencesUniversity of AntwerpAntwerpBelgium A Division of the National Health Laboratory ServiceJohannesburgSouth Africa Sexually Transmitted Infection Unit Institute of Tropical MedicineAntwerpBelgium Third Affiliated Hospital Sun Yat-Sen UniversityGuangzhouChina Thermo Fisher Scientific LandsmeerThe Netherlands Mycology Unit and IISPV University Rovira i VirgiliReusTarragonaSpain

The family Ajellomycetaceae(Onygenales)includes mammal-associated pathogens within the genera Blastomyces,Emmonsia,Histoplasma and Paracoccidioides,as well as the recently described genera,Emergomyces that causes disease in immunocompromised hosts,and Emmonsiellopsis,known only from *** further assess the phylogenetic relationships among and between members of these genera and several previously undescribed species,we sequenced and analyzed the DNA-directed RNA polymerase II(rPB2),translation elongation factor 3-a(TEF3),b-tubulin(TUB2),28S large subunit rDNA(LSU)and the internal transcribed spacer regions(ITS)in 68 strains,in addition to morphological and physiological *** better understand the thermal dimorphism among these fungi,the dynamic process of transformation from mycelial to yeast-like or adiaspore-like forms was also assessed over a range of temperatures(6–42C).Molecular data resolved the relationships and recognized five major well-supported lineages that correspond largely to the genus ***,typified by Emmonsia parva,is a synonym of Blastomyces that also accommodates Blastomyces helicus(formerly Emmonsia helica).Emmonsia crescens is phylogenetically distinct,and found closely related to a single strain from soil without known *** silverae,Emergomyces canadensis,Emergomyces europaeus and Emmonsia sola are newly *** all of the taxa are associated with human and animal *** crescens,*** and *** are prevalently associated with pulmonary disease in humans or *** helicus,***,Emergomyces africanus,***,***,*** and ***(formerly Emmonsia pasteuriana)are predominantly found in human hosts with immune disorders;no animal hosts are known for these species except ***.

关键词： Ajellomycetaceae Onygenales Phylogeny Ecology Thermal dimorphism Systemic infection Taxonomy

The world’s ten most feared fungi

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Fungal Diversity 2018年第6期93卷 161-194页

作者： Kevin D.Hyde Abdullah M.S.Al-Hatmi Birgitte Andersen Teun Boekhout Walter Buzina Thomas L.Dawson Jr. Dan C.Eastwood E.B.Gareth Jones Sybren de Hoog Yingqian Kang Joyce E.Longcore Eric H.C.McKenzie Jacques F.Meis Laetitia Pinson-Gadais Achala R.Rathnayaka Florence Richard-Forget Marc Stadler Bart Theelen Benjarong Thongbai Clement K.M.Tsui Key Laboratory for Plant Diversity and Biogeography of East Asia Kunming Institute of BotanyChinese Academy of SciencesKunming 650201YunnanPeople’s Republic of China Center of Excellence in Fungal Research Mae Fah Luang UniversityChiang Rai 57100Thailand Ministry of Health Directorate General of Health ServicesIbriOman Department of Biotechnology and Biomedicine Technical University of Denmark2800 Kgs.LyngbyDenmark Institute for Biodiversity and Ecosystem Dynamics(IBED) University of AmsterdamAmsterdamThe Netherlands Westerdijk Fungal Biodiversity Institute UtrechtThe Netherlands R&D Institute for Hygiene Microbiology and Environmental MedicineMedical University GrazNeue Stiftingtalstrasse 68010 GrazAustria Institute for Medical Biology(IMB) Agency for ScienceTechnologyand Research(A_(*)STAR)SingaporeSingapore Departments of Drug Discovery and Biomedical Sciences and Biochemistry and Molecular Biology Center for Cell DeathInjury and RegenerationMedical University of South CarolinaCharlestonSCUSA Department of Bioscience Academic Office102First FloorWallace BuildingSwansea UniversitySingleton CampusSwanseaWalesUK Centre of Expertise in Mycology radboudumc/Canisius Wilhelmina Hospital(CWZ) NijmegenThe Netherlands Portsmouth Hampshire PO53DHUK Department of Microbiology and the Key Laboratory of Proteomics Guizhou Medical UniversityGuiyangChina School of Biology and Ecology University of MaineOronoME 04469USA Manaaki Whenua-Landcare Research Private Bag 92170AucklandNew Zealand Department of Medical Microbiology and Infectious Diseases Canisius Wilhelmina Hospital(CWZ)NijmegenThe Netherlands INRA UR1264 MycSA71 av Edouard Bourlaux2003233882 Villenave D’Ornon CedexFrance Department Microbial Drugs Helmholtz Centre for Infection Researchand German Centre for Infection Research(DZIF)Partner Site Hannover-BraunschweigInhoffenstraße 738124 BraunschweingGermany Department of Pathology Sidra MedicineDohaQatar Department of Pathology and Laboratory Medicine Weill Corne

An account is provided of the world’s ten most feared *** areas of interest,we have organized the entries in the order of *** put four human pathogens first as this is of concern to most *** is followed by fungi producing mycotoxins that are highly harmful for humans;Aspergillus flavus,the main producer of aflatoxins,was used as an *** due to indoor air fungi may also directly affect our health and we use Stachybotrys chartarum as an *** everyone collects and eats edible ***,fatalities caused by mushroom intoxications often make news headlines and therefore we include one of the most poisonous of all mushrooms,Amanita phalloides,as an *** then move on to the fungi that damage our dwellings causing serious anxiety by rotting our timber structures and *** lacrymans,which causes dry rot is an excellent *** next example serves to represent all plant and forest *** we chose Austropuccinia psidii as it is causing devastating effects in Australia and will probably do likewise in New ***,we chose an important amphibian pathogen which is causing serious declines in the numbers of frogs and other amphibians *** we target the top ten most feared fungi,numerous others are causing serious concern to human health,plant production,forestry,other animals and our factories and *** highlighting ten feared fungi as an example,we aim to promote public awareness of the cost and importance of fungi.

关键词： Aflatoxicosis Batrachochytrium Candida auris Frog decline Poisonous fungi Human pathogens Indoor fungi Forest pathogens Wood decay