2022
Treating ‘Septic’ With Enhanced Antibiotics and ‘Arthritis’ by Mitigation of Excessive Inflammation
Kwon HK, Dussik CM, Kim SH, Kyriakides TR, Oh I, Lee FY. Treating ‘Septic’ With Enhanced Antibiotics and ‘Arthritis’ by Mitigation of Excessive Inflammation. Frontiers In Cellular And Infection Microbiology 2022, 12: 897291. PMID: 35755835, PMCID: PMC9218192, DOI: 10.3389/fcimb.2022.897291.Peer-Reviewed Original ResearchConceptsSeptic arthritisBacterial burdenAntibiotic treatmentMurine modelTherapeutic goalsConcurrent antimicrobial therapyDistinct therapeutic goalsGeneration of inflammationMRSA septic arthritisSeptic knee arthritisInflammatory joint conditionsArticular cartilageMitigation of inflammationPost-antibiotic treatmentNovel therapeutic strategiesSeptic arthritis modelArticular cartilage damageEx vivo modelArticular cartilage integrityInflammatory arthritisInhibitors of ERKInflammatory profileMRSA infectionSynovial tissueExcessive inflammation
2021
Dual therapeutic targeting of intra-articular inflammation and intracellular bacteria enhances chondroprotection in septic arthritis
Kwon HK, Lee I, Yu KE, Cahill SV, Alder KD, Lee S, Dussik CM, Back J, Choi J, Song L, Kyriakides TR, Lee FY. Dual therapeutic targeting of intra-articular inflammation and intracellular bacteria enhances chondroprotection in septic arthritis. Science Advances 2021, 7: eabf2665. PMID: 34172438, PMCID: PMC8232912, DOI: 10.1126/sciadv.abf2665.Peer-Reviewed Original ResearchConceptsIntra-articular inflammationSeptic arthritisBacterial infectionsDual therapeutic targetingKnee septic arthritisPromising new therapeutic strategyArticular cartilageChallenging clinical problemNovel treatment modalitiesIntracellular bacteriaNew therapeutic strategiesAdjuvant targetingTreatment modalitiesBacterial eradicationSuccessful treatmentHost inflammationCausative bacteriaMurine modelTherapeutic strategiesArthritisTherapeutic goalsClinical problemTherapeutic targetingInflammationVital organsBiocompatibility of platinum-based bulk metallic glass in orthopedic applications
Loye AM, Kwon HK, Dellal D, Ojeda R, Lee S, Davis R, Nagle N, Doukas PG, Schroers J, Lee FY, Kyriakides TR. Biocompatibility of platinum-based bulk metallic glass in orthopedic applications. Biomedical Materials 2021, 16: 045018. PMID: 33873168, DOI: 10.1088/1748-605x/abf981.Peer-Reviewed Original ResearchConceptsBulk metallic glassPt-BMGPlatinum-based bulk metallic glassMetallic glassesConventional metallic implantsCorrosion resistanceHigh strengthMechanical testingOrthopedic applicationsBone applicationsMetallic implantsMicro-computed tomographyAmorphous metalsTitaniumWearBiocompatibilitySimilar biocompatibilityFurther processingGlassDuctilityNanopatternsNanoscaleApplicationsMesenchymal stem cellsStrengthLoss of endothelial glucocorticoid receptor promotes angiogenesis via upregulation of Wnt/β-catenin pathway
Liu B, Zhou H, Zhang T, Gao X, Tao B, Xing H, Zhuang Z, Dardik A, Kyriakides TR, Goodwin JE. Loss of endothelial glucocorticoid receptor promotes angiogenesis via upregulation of Wnt/β-catenin pathway. Angiogenesis 2021, 24: 631-645. PMID: 33650028, PMCID: PMC8292305, DOI: 10.1007/s10456-021-09773-x.Peer-Reviewed Original ResearchConceptsWnt/β-catenin signalingWnt/β-catenin pathwayΒ-catenin signalingΒ-catenin pathwayAutophagy fluxKey biological processesGlucocorticoid receptorNuclear receptor familyTube formation assaysEndothelial cellsBiological processesCanonical WntP62 degradationReceptor familyFormation assaysAbsence of GRCell viability assaysProcess of angiogenesisWntGR regulationSignalingVivo assaysQuantitative PCRKey receptorPathway
2019
Elevated Thrombospondin 2 Contributes to Delayed Wound Healing in Diabetes
Kunkemoeller B, Bancroft T, Xing H, Morris AH, Luciano AK, Wu J, Fernandez-Hernando C, Kyriakides TR. Elevated Thrombospondin 2 Contributes to Delayed Wound Healing in Diabetes. Diabetes 2019, 68: 2016-2023. PMID: 31391172, PMCID: PMC6754242, DOI: 10.2337/db18-1001.Peer-Reviewed Original ResearchConceptsThrombospondin-2TSP2 expressionDiabetic control miceWound healingEffects of hyperglycemiaImpaired wound healingUnderlying pathological mechanismsDelayed Wound HealingMajor cellular sourceBlood vessel maturationGranulation tissue formationMajor complicationsDiabetic miceControl miceTreatment strategiesDiabetesPathological mechanismsDiabetic woundsAccelerated reepithelializationCellular sourceHigh glucoseHyperglycemiaMatricellular proteinExpression contributesHexosamine pathwayThrombospondin-2 regulates extracellular matrix production, LOX levels, and cross-linking via downregulation of miR-29
Calabro NE, Barrett A, Chamorro-Jorganes A, Tam S, Kristofik NJ, Xing H, Loye AM, Sessa WC, Hansen K, Kyriakides TR. Thrombospondin-2 regulates extracellular matrix production, LOX levels, and cross-linking via downregulation of miR-29. Matrix Biology 2019, 82: 71-85. PMID: 30876926, PMCID: PMC6710120, DOI: 10.1016/j.matbio.2019.03.002.Peer-Reviewed Original ResearchConceptsECM protein productionProtein productionLysyl oxidaseThrombospondin-2MiR-29Matricellular proteinQuantitative proteomics approachLevels of LOXExtracellular matrix productionProteomic approachECM proteinsMajor regulatorECM homeostasisExtracellular matrixMatrix productionProteinCollagen fibrillogenesisMiR-29 expressionFibrillar collagenImportant modulatorDependent processesLOX levelsRegulatorProductionHomeostasis
2018
Tunable Hydrogels Derived from Genetically Engineered Extracellular Matrix Accelerate Diabetic Wound Healing
Morris AH, Lee H, Xing H, Stamer DK, Tan M, Kyriakides TR. Tunable Hydrogels Derived from Genetically Engineered Extracellular Matrix Accelerate Diabetic Wound Healing. ACS Applied Materials & Interfaces 2018, 10: 41892-41901. PMID: 30424595, PMCID: PMC9996546, DOI: 10.1021/acsami.8b08920.Peer-Reviewed Original ResearchDecellularized materials derived from TSP2-KO mice promote enhanced neovascularization and integration in diabetic wounds
Morris AH, Stamer DK, Kunkemoeller B, Chang J, Xing H, Kyriakides TR. Decellularized materials derived from TSP2-KO mice promote enhanced neovascularization and integration in diabetic wounds. Biomaterials 2018, 169: 61-71. PMID: 29631168, PMCID: PMC5933884, DOI: 10.1016/j.biomaterials.2018.03.049.Peer-Reviewed Original ResearchConceptsUltimate tensile strengthECM-based materialsTensile strengthMechanical testingDecellularized materialsElastic modulusSynthetic biomaterialsIntact slabsMatrix propertiesExtracellular matrix propertiesCell-derived ECMBiologic scaffoldsElectron microscopyEngineering controlsMaterialsWtEfficient integrationEnhanced vascularizationModulusPromigratory propertiesScaffoldsPropertiesBiomaterialsEnhanced remodelingGreater cell migration
2017
Improving in vivo outcomes of decellularized vascular grafts via incorporation of a novel extracellular matrix
Kristofik NJ, Qin L, Calabro NE, Dimitrievska S, Li G, Tellides G, Niklason LE, Kyriakides TR. Improving in vivo outcomes of decellularized vascular grafts via incorporation of a novel extracellular matrix. Biomaterials 2017, 141: 63-73. PMID: 28667900, PMCID: PMC5918415, DOI: 10.1016/j.biomaterials.2017.06.025.Peer-Reviewed Original ResearchConceptsUnmodified graftsVascular graftsCoronary bypass proceduresMechanical propertiesMural cell recruitmentBypass proceduresRat aortaMMP levelsCell recruitmentDecreased failure rateGraftPlatelet studiesGraft mechanical propertiesNative vesselsShelf vascular graftsSmall-diameter vascular graftsTime pointsExtracellular matrixDiameter vascular graftsTensile strengthYoung's modulusWT cellsPresent studySuture retentionFailure rateA hidden structural vulnerability in the thrombospondin-2 deficient aorta increases the propensity to intramural delamination
Bellini C, Kristofik NJ, Bersi MR, Kyriakides TR, Humphrey JD. A hidden structural vulnerability in the thrombospondin-2 deficient aorta increases the propensity to intramural delamination. Journal Of The Mechanical Behavior Of Biomedical Materials 2017, 71: 397-406. PMID: 28412645, PMCID: PMC8344363, DOI: 10.1016/j.jmbbm.2017.01.045.Peer-Reviewed Original Research
2016
Impaired von Willebrand factor adhesion and platelet response in thrombospondin-2 knockout mice
Kristofik N, Calabro NE, Tian W, Meng A, MacLauchlan S, Wang Y, Breuer CK, Tellides G, Niklason LE, Kyriakides TR. Impaired von Willebrand factor adhesion and platelet response in thrombospondin-2 knockout mice. Blood 2016, 128: 1642-1650. PMID: 27471233, PMCID: PMC5034742, DOI: 10.1182/blood-2016-03-702845.Peer-Reviewed Original ResearchNanoparticle delivery of miR-223 to attenuate macrophage fusion
Moore LB, Sawyer AJ, Saucier-Sawyer J, Saltzman WM, Kyriakides TR. Nanoparticle delivery of miR-223 to attenuate macrophage fusion. Biomaterials 2016, 89: 127-135. PMID: 26967647, PMCID: PMC4924476, DOI: 10.1016/j.biomaterials.2016.02.036.Peer-Reviewed Original ResearchConceptsForeign body giant cellsMiR-223 mimicsMiR-223Foreign body responseMacrophage fusionSubsequent cytoskeletal rearrangementMiR microarrayKO miceRole of microRNAsMolecular mediatorsNegative regulatorGiant cellsPrimary macrophagesFusion of macrophagesNovel mediatorPrecise mechanismFusion-competent stateTherapeutic inhibitorsBody responseMacrophagesNanoparticle deliveryImplant modelMediatorsEventual encapsulationPost-transcriptional level
2014
Engineering Cellular Response Using Nanopatterned Bulk Metallic Glass
Padmanabhan J, Kinser ER, Stalter MA, Duncan-Lewis C, Balestrini JL, Sawyer AJ, Schroers J, Kyriakides TR. Engineering Cellular Response Using Nanopatterned Bulk Metallic Glass. ACS Nano 2014, 8: 4366-4375. PMID: 24724817, PMCID: PMC4046793, DOI: 10.1021/nn501874q.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiocompatible MaterialsBiomechanical PhenomenaCell AdhesionCell SurvivalCollagenCytoskeletonFibroblastsFibronectinsForeign-Body ReactionGlassGTP PhosphohydrolasesHuman Umbilical Vein Endothelial CellsHumansMetalsMiceMicroscopy, FluorescenceNanostructuresNanotechnologyNIH 3T3 CellsProtein EngineeringRhoA GTP-Binding ProteinConceptsBulk metallic glassCellular responsesFeature sizeMetallic glassesFocal adhesion densityCell traction forcesCytoskeletal remodelingFIB-SEM techniqueSubstrate stiffnessBiomechanical cuesThermoplastic formingMolecular pathwaysCell typesVersatile fabricationNondimensional analysisSubstrate nanotopographyCellular morphologyCell morphologyBiocompatible materialsCell functionForeign body responseNanoscale precisionCell sizeTissue repairFibroblasts
2011
Inflammasome components Asc and caspase-1 mediate biomaterial-induced inflammation and foreign body response
Malik AF, Hoque R, Ouyang X, Ghani A, Hong E, Khan K, Moore LB, Ng G, Munro F, Flavell RA, Shi Y, Kyriakides TR, Mehal WZ. Inflammasome components Asc and caspase-1 mediate biomaterial-induced inflammation and foreign body response. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 20095-20100. PMID: 22109549, PMCID: PMC3250158, DOI: 10.1073/pnas.1105152108.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAnimalsApoptosis Regulatory ProteinsAspirinBiocompatible MaterialsCalcium-Binding ProteinsCARD Signaling Adaptor ProteinsCarrier ProteinsCaspase 1Cluster AnalysisCytoskeletal ProteinsForeign-Body ReactionGiant CellsInflammasomesInflammationInterleukin-1betaMacrophages, PeritonealMembrane MicrodomainsMiceMice, Inbred C57BLMicrospheresNLR Family, Pyrin Domain-Containing 3 ProteinPolymethyl Methacrylate
2004
The CC Chemokine Ligand, CCL2/MCP1, Participates in Macrophage Fusion and Foreign Body Giant Cell Formation
Kyriakides TR, Foster MJ, Keeney GE, Tsai A, Giachelli CM, Clark-Lewis I, Rollins BJ, Bornstein P. The CC Chemokine Ligand, CCL2/MCP1, Participates in Macrophage Fusion and Foreign Body Giant Cell Formation. American Journal Of Pathology 2004, 165: 2157-2166. PMID: 15579457, PMCID: PMC1618731, DOI: 10.1016/s0002-9440(10)63265-8.Peer-Reviewed Original ResearchConceptsForeign body giant cellsForeign body reactionCC chemokine ligand 2CCL2-null miceChemokine ligand 2CC chemokine ligandBlood-borne monocytesPeripheral blood monocytesWild-type miceCCL2/MCP1Chemokine ligandGiant cell formationMonocyte recruitmentBlood monocytesFBGC formationMacrophage fusionGiant cellsImplantation sitesBody reactionForeign body giant cell formationMiceInhibitory peptidesCCL2 functionMonocytesChemotactic signals
2001
Altered Extracellular Matrix Remodeling and Angiogenesis in Sponge Granulomas of Thrombospondin 2-Null Mice
Kyriakides T, Zhu Y, Yang Z, Huynh G, Bornstein P. Altered Extracellular Matrix Remodeling and Angiogenesis in Sponge Granulomas of Thrombospondin 2-Null Mice. American Journal Of Pathology 2001, 159: 1255-1262. PMID: 11583953, PMCID: PMC1850515, DOI: 10.1016/s0002-9440(10)62512-6.Peer-Reviewed Original ResearchConceptsTSP2-null miceMatrix remodelingWild-type miceMatrix metalloproteinase-2Wild-type animalsExtracellular matrix remodelingModulators of angiogenesisFibrogenic responseImmunohistochemical analysisMetalloproteinase-2Minimal scarringMMP2 levelsSponge granulomaAngiogenesis inhibitorsMice displayVivo evidenceThrombospondin-2MiceGrowth factorImportant modulatorTissue invasionTSP2-nullWound healingAngiogenesisSignificant differencesThrombospondin‐2 plays a protective role in multistep carcinogenesis: a novel host anti‐tumor defense mechanism
Hawighorst T, Velasco P, Streit M, Hong Y, Kyriakides T, Brown L, Bornstein P, Detmar M. Thrombospondin‐2 plays a protective role in multistep carcinogenesis: a novel host anti‐tumor defense mechanism. The EMBO Journal 2001, 20: 2631-2640. PMID: 11387198, PMCID: PMC125494, DOI: 10.1093/emboj/20.11.2631.Peer-Reviewed Original ResearchMeSH Keywords9,10-Dimethyl-1,2-benzanthraceneAnimalsApoptosisCell Adhesion MoleculesCell DivisionDisease SusceptibilityEndothelial Growth FactorsFemaleGene Expression Regulation, NeoplasticLymphokinesMiceMice, Inbred StrainsMice, KnockoutNeovascularization, PathologicOligodeoxyribonucleotides, AntisensePapillomaPrecancerous ConditionsSkinSkin NeoplasmsThrombospondinsTime FactorsTranscription, GeneticVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsConceptsWild-type miceTSP-2 expressionThrombospondin-2Angiogenic switchTumor formationMultistep carcinogenesisVascular endothelial growth factorAnti-angiogenic factorsTSP-2-deficient miceEndothelial growth factorAngiogenesis inhibitor thrombospondin-2Endogenous angiogenesis inhibitorTumor cell apoptosisTumor differentiationMesenchymal stromaMulti-step tumorigenesisDefense mechanismsAngiogenesis inhibitorsProtective roleAngiogenesis factorsTumor angiogenesisTumor cellsGrowth factorCell apoptosisRegulation of Angiogenesis and Matrix Remodeling by Localized, Matrix-Mediated Antisense Gene Delivery
Kyriakides T, Hartzel T, Huynh G, Bornstein P. Regulation of Angiogenesis and Matrix Remodeling by Localized, Matrix-Mediated Antisense Gene Delivery. Molecular Therapy 2001, 3: 842-849. PMID: 11407897, DOI: 10.1006/mthe.2001.0336.Peer-Reviewed Original Research
2000
Thrombospondin 2, a matricellular protein with diverse functions
Bornstein P, Armstrong L, Hankenson K, Kyriakides T, Yang Z. Thrombospondin 2, a matricellular protein with diverse functions. Matrix Biology 2000, 19: 557-568. PMID: 11102746, DOI: 10.1016/s0945-053x(00)00104-9.Peer-Reviewed Original ResearchConceptsMatrix metalloproteinase-2TSP2-null miceThrombospondin-2Matricellular proteinConnective tissueGrowth of tumorsConnective tissue elementsFragility of skinFunctional abnormalitiesTissue injuryMetalloproteinase-2MMP2 activityBleeding defectMiceCell surface receptorsGrowth factorAdult animalsMode of actionBone growthMarked disparityTissue elementsSubdermal tissueAbnormalitiesDermal fibroblastsTissueThrombospondin 2 Modulates Collagen Fibrillogenesis and Angiogenesis
Bornstein P, Kyriakides T, Yang Z, Armstrong L, Birk D. Thrombospondin 2 Modulates Collagen Fibrillogenesis and Angiogenesis. Journal Of Investigative Dermatology Symposium Proceedings 2000, 5: 61-66. PMID: 11147677, DOI: 10.1046/j.1087-0024.2000.00005.x.Peer-Reviewed Original ResearchConceptsVascular densityTSP2-null miceMatrix metalloproteinase-2 productionMetalloproteinase-2 productionConnective tissue abnormalitiesFlexor muscle tendonsExcisional skin woundsPolyvinyl alcohol spongesSilicone rubber discsAbnormal collagen fibrilsMuscle tendonSubcutaneous tissueNull miceTissue abnormalitiesDistinct abnormalitiesEndothelial cellsThrombospondin-2Matricellular proteinAlcohol spongesTHBS2 geneCell functionCell-matrix interactionsMiceSkin woundsMode of action