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Biofabrication of nanocomposite-based scaffolds containing human bone extracellularmatrix for the differentiation of skeletal stem and progenitor cells

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Bio-Design and Manufacturing 2024年第2期7卷 121-136页

作者： Yang-Hee Kim Janos M.Kanczler Stuart Lanham Andrew Rawlings Marta Roldo gianluca Tozzi Jonathan I.Dawson gianluca cidonio Richard O.c.Oreffo Faculty of Medicine Bone and Joint Research GroupCentre for Human DevelopmentStem Cells and RegenerationInstitute of Developmental SciencesUniversity of SouthamptonSouthampton SO166YDUK School of Pharmacy and Biomedical Science University of PortsmouthPortsmouth PO12DTUK School of Engineering Faculty of Engineering and ScienceUniversity of GreenwichGreenwich ME44TBUK center for Life Nano-and Neuro-Science(cLN2S) Italian Institute of Technology00161 RomeItaly

Autograft or metal implants are routinely used in skeletal repair.However,they fail to provide long-term clinical resolution,necessitating a functional biomimetic tissue engineering alternative.The use of native human bone tissue for synthesizing a biomimeticmaterial inkfor three-dimensional(3D)bioprintingof skeletal tissueis anattractivestrategyfor tissueregeneration.Thus,human bone extracellular matrix(bone-EcM)offers an exciting potential for the development of an appropriate microenvironment for human bone marrow stromal cells(HBMScs)to proliferate and differentiate along the osteogenic lineage.In this study,we engineered a novel material ink(LAB)by blending human bone-EcM(B)with nanoclay(L,Laponite®)and alginate(A)polymers using extrusion-based deposition.The inclusion of the nanoﬁller and polymeric material increased the rheology,printability,and drug retention properties and,critically,the preservation of HBMScs viability upon printing.The composite of human bone-EcM-based 3D constructs containing vascular endothelial growth factor(VEGF)enhanced vascularization after implantation in an ex vivo chick chorioallantoic membrane(cAM)model.The inclusion of bone morphogenetic protein-2(BMP-2)with the HBMScs further enhanced vascularization and mineralization after only seven days.This study demonstrates the synergistic combination of nanoclay with biomimetic materials(alginate and bone-EcM)to support the formation of osteogenic tissue both in vitro and ex vivo and offers a promising novel 3D bioprinting approach to personalized skeletal tissue repair.

关键词： Extracellular matrix Nanoclay Bone 3D bioprinting

Heavy ion induced charge exchange reactions: A preliminary study within the constrained Molecular Dynamics model

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chinese Physics c 2021年第8期45卷 105-109页

作者： gianluca Giuliani School of Nuclear Science and Technology Lanzhou UniversitySouth Tianshui Road222Lanzhou 730000China

We present a preliminary study of charge exchange heavy ion induced reactions based on the constrained molecular dynamics(coMD)model.The purpose is to test the capability of the model in predicting the occurrence of single charge exchange(ScE)and double charge exchange(DcE)exit channels for three different en-trance channels at the same laboratory incident energy.The nuclear reaction dynamics and nuclear interaction within the coMD approach are the only ingredients that have given,at this stage,promising results for ScE and DcE cross section calculations.The obtained results suggest an upgrade and possible future employment of the model for studies relating to the production of exotic nuclei through charge exchange reactions or DcE reactions and their connection with neutrinoless double beta decay.

关键词： nuclear physics nuclear reactions molecular dynamics

Salivary biomarkers: novel noninvasive tools to diagnose chronic inflammation

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International Journal of Oral Science 2023年第2期15卷 229-240页

作者： Paola Dongiovanni Marica Meroni Sara casati Riccardo Goldoni Douglas Vieira Thomaz Nermin Seda Kehr Daniela Galimberti Massimo Del Fabbro gianluca MTartaglia Medicine and Metabolic Diseases Fondazione IRCCS CàGranda Ospedale Maggiore Policlinico Department of Biomedical Surgical and Dental SciencesUniversity of Milan Department of Electronics Information and Bioengineering(DEIB) Istituto di Elettronica e di Ingegneria dell'Informazione e delle Telecomunicazioni CNR Laboratory of Medicinal Pharmaceutical chemistry Faculty of PharmacyFederal University of Goiás Department of chemistry ?zmir Institute of TechnologyGülbah?e Kampüsü Neurology-Neurodegenerative Diseases Fondazione IRCCS CàGrandaOspedale Maggiore Policlinico UOc Maxillo-Facial Surgery and Dentistry Fondazione IRccS càGranda Ospedale Maggiore Policlinico

Several chronic disorders including type 2 diabetes(T2D),obesity,heart disease and cancer are preceded by a state of chronic lowgrade inflammation.Biomarkers for the early assessment of chronic disorders encompass acute phase proteins(APP),cytokines and chemokines,pro-inflammatory enzymes,lipids and oxidative stress mediators.These substances enter saliva through the blood flow and,in some cases。

关键词： inflammation acute chronic

clinical Significance of Apurinic/Apyrimidinic Endodeoxyribonuclease 1 and MicroRNA Axis in Hepatocellular carcinoma

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Journal of clinical and Translational Hepatology 2023年第6期11卷 1291-1307页

作者： Giovanna Mangiapane Devis Pascut Emiliano Dalla Giulia Antoniali Monica Degrassi Lory Saveria crocè Veronica De Sanctis Silvano Piazza Giulia canarutto claudio Tiribelli gianluca Tell Laboratory of Molecular Biology and DNA Repair Department of MedicineUniversity of UdineUdineItaly Fondazione Italiana Fegato-ONLUS Liver Cancer UnitTriesteItaly Department of Medical Sciences University of TriesteTriesteItaly clinica Patologie Fegato Azienda Sanitaria Universitaria Giuliano Isontina(ASUGI)TriesteItaly NGS core Facility Department CIBIOUniversity of TrentoTrentoItaly computational Biology International Centre for Genetic Engineering and BiotechnologyICGEBTriesteItaly

Background and Aims:Identification of prognostic factors for hepatocellular carcinoma(Hcc)opens new perspectives for therapy.circulating and cellular onco-miRNAs are noncoding RNAs which can control the expression of genes involved in oncogenesis through post-transcriptional mechanisms.These microRNAs(miRNAs)are considered novel prognostic and predictive factors in Hcc.The apurinic/apyrimidinic endodeoxyribonuclease 1(APE1)contributes to the quality control and processing of specific onco-miRNAs and is a negative prognostic factor in several tumors.The present work aims to:a)define APE1 prognostic value in Hcc;b)identify miRNAs regulated by APE1 and their relative target genes and c)study their prognostic value.Methods:We used The cancer Genome Atlas(commonly known as TcGA)data analysis to evaluate the expression of APE1 in Hcc.To identify differentially-expressed miRNAs(DEmiRNAs)upon APE1 depletion through specific small interfering RNA,we used NGS and nanostring approaches in the JHH-6 Hcc tumor cell line.Bioinformatics analyses were performed to identify signaling pathways involving APE1-regulated miRNAs.Microarray analysis was performed to identify miRNAs correlating with serum APE1 expression.Results:APE1 is considerably overexpressed in Hcc tissues compared to normal liver,according to the TcGA-liver Hcc(known as LIHc)dataset.Enrichment analyses showed that APE1-regulated miRNAs are implicated in signaling and metabolic pathways linked to cell proliferation,transformation,and angiogenesis,identifying cyclin Dependent Kinase 6 and Lysosomal Associated Membrane Protein 2 as targets.miR-33a-5p,miR-769,and miR-877 are related to lower overall survival in Hcc patients.Through array profiling,we identified eight circulating DE-miRNAs associated with APE1 overexpression.A training phase identified positive association between sAPE1 and miR-3180-3p and miR-769.conclusions:APE1 regulates specific miRNAs having prognostic value in Hcc.

关键词： APE1 miRNAs Prognostic factors Hepatocellular carcinoma

Spinal Motion Segments-Ⅱ:Tuning and Optimisation for Biofidelic Performance

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Journal of Bionic Engineering 2020年第4期17卷 757-766页

作者： constantinos Franceskides Emily Arnold Ian Horsfall gianluca Tozzi Michael cGibson Peter Zioupos Musculoskeletal and Medicolegal Research Group Cranfield Forensic InstituteCranfield UniversityDefence Academy of the UKShrivenhamSN68LAUK centre for Defence Engineering Cranfield UniversityDefence Academy of the UKShrivenhamSN68LAUK School of Engineering University of PortsmouthPortsmouthPO13DJUK centre for Simulation&Analytics Cranfield UniversityDefence Academy of the UKShrivenhamSN68LAUK

Most commercially available spine analogues are not intended for biomechanical testing,and the few that are suitable for using in conjunction with implants and devices to allow a hands-on practice on operative procedures are very expensive and still none of these offers patient-specific analogues that can be accessed within reasonable time and price range.Man-made spine analogues would also avoid the ethical restrictions surrounding the use of biological specimens and complications arising from their inherent biological variability.Here we sought to improve the biofidelity and accuracy of a patient-specific motion segment analogue that we presented recently.These models were made by acrylonitrile butadiene styrene(ABS)in 3D printing of porcine spine segments(T12-L5)from microcT scan data,and were tested in axial loading at 0.6 mm.min-1(strain rate range 6×10^-4 s^-1-10×10^-4 s^-1).In this paper we have sought to improve the biofidelity of these analogue models by concentrating in improving the two most critical aspects of the mechanical behaviour:the material used for the intervertebral disc and the influence of the facet joints.The deformations were followed by use of Digital Image correlation(DIc)and consequently different scanning resolutions and data acquisition techniques were also explored and compared to determine their effect.We found that the selection of an appropriate intervertebral disc simulant(PT Flex 85)achieved a realistic force/displacement response and also that the facet joints play a key role in achieving a biofidelic behaviour for the entire motion segment.We have therefore overall confirmed the feasibility of producing,by rapid and inexpensive 3D-printing methods,high-quality patient-specific spine analogue models suitable for biomechanical testing and practice.

关键词： spine bone analogue micro-cT 3D printing Digital Image correlation(DIc)

Spinal Motion Segments-Ⅰ:concept for a Subject-specific Analogue Model

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Journal of Bionic Engineering 2020年第4期17卷 747-756页

作者： constantinos Franceskides Emily Arnold Ian Horsfall gianluca Tozzi Michael cGibson Peter Zioupos Musculoskeletal and Medicolegal Research Group Cranfield Forensic InstituteCranfield UniversityDefence Academy of the UKShrivenhamSN68LAUK Impact and Armour Group Centre for Defence EngineeringCranfield UniversityDefence Academy of the UKShrivenhamSN68LAUK School of Engineering University of PortsmouthPortsmouthPO13DJUK centre for Simulation&Analytics Cranfield UniversityDefence Academy of the UKShrivenhamSN68LAUK

Most commercial spine analogues are not intended for biomechanical testing,and those developed for this purpose are expensive and yet still fail to replicate the mechanical performance of biological specimens.Patient-specific analogues that address these limitations and avoid the ethical restrictions surrounding the use of human cadavers are therefore required.We present a method for the production and characterisation of biofidelic,patient-specific,Spine Motion Segment(SMS=2 vertebrae and the disk in between)analogues that allow for the biological variability encountered when dealing with real patients.Porcine spine segments(L1-LA)were scanned by computed tomography,and 3D models were printed in acrylonitrile butadiene styrene(ABS).Four biological specimens and four ABS motion segments were tested,three of which were further segmented into two Vertebral Bodies(VBs)with their intervertebral disc(IVD).All segments were loaded axially at 0.6 mm·min-1(strain-rate range 6×10-4 s-1-10×10-4 s-1).The artificial VBs behaved like biological segments within the elastic region,but the best two-part artificial IVD were^15%less stiffthan the biological IVDs.High-speed images recorded during compressive loading allowed full-field strains to be produced.During compression of the spine motion segments,IVDs experienced higher strains than VBs as expected.Our method allows the rapid,inexpensive and reliable production of patient-specific 3D-printed analogues,which morphologically resemble the real ones,and whose mechanical behaviour is comparable to real biological spine motion segments and this is their biggest asset.

关键词： spine bone analogue micro-cT 3D printing Digital Image correlation(DIc)

Ops!... Where is my left main？

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Journal of Geriatric cardiology 2018年第9期15卷 609-610页

作者： gianluca Rigatelli Mario Lupia Marco Zuin cardiovascular Diagnosis and Endoluminal hlterventions Unit Rovigo General Hospital Rovigo Italy Vascular Surgery Padua University School of Medicine. Padua Italy Section of Internal and cardiopuhnonary Medicine Department of Medical Science University of Ferrara Ferrara Italy

coronary artery anomalies can reach easily nowadays elderly age, causing troubles at both diagnostic and therapeutic levels. A 80-year-old hypertensive man underwent coronary artery angiography because of a doubtful ergometric test for atypical thoracic discomfort. The left main was absent in the left coronary sinus (Figure 1A). Selective right coronary artery (RcA) angiography showed a RcA which continued at level of the posterolateral branch with the left circumflex coronary artery (Lcx) and retrogradely ended into a left anterior coronary artery (LAD) (Figure 1B and 1c).

关键词： Ops tic 高血压动脉

comparison of 2D and 4D Flow MRI Measurements for Hemodynamic Evaluation of the Fontan Palliation

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congenital Heart Disease 2023年第6期18卷 627-638页

作者： Elisa Listo Nicola Martini Stefano Salvadori Elisa Valenti Nicola Stagnaro gianluca Trocchio chiara Marrone Alberto clemente Francesca Raimondi Pierluigi Festa Lamia Ait Ali Department of Radiology IRCCS Istituto Giannina GasliniGenovaItaly U.O.c.Bioingegneria Gabriele Monasterio CNR-Tuscany FoundationPisaItaly Institute of clinical Physiology cNR PisaItaly cardiology Unit IRCCS Istituto Giannina GasliniGenovaItaly Pediatric cardiology and GUcH Unit Massa Gabriele Monasterio CNR-Tuscany FoundationMassaItaly Gabriele Monasterio cNR-Tuscany Foundation PisaItaly Department of cardiology Azienda Ospedaliero-Universitaria MeyerFlorenceItaly Institute of clinical Physiology cNR MassaItaly

Background:The assessment of Fontan circuit’sﬂow is traditionally evaluated by multiple through-plane phase-contrast MRI acquisitions(2Dﬂow),while recently,a single volumetric 4D-ﬂow MRI acquisition is emerging as a comprehensive tool for the hemodynamic evaluation in congenital heart diseases.Purpose:To compare 2D and 4D-ﬂow MRI measurements in patients after Fontan palliation and to evaluate parameters affecting potential dis-agreement.Methods:39 patients after Fontan palliation(23 males,age 22±11 years)who underwent cardiac MRI with 2D and 4D-ﬂow MRI acquisition were included in the study.In all patients,bloodﬂow quantiﬁcation in the Fontan circuit and aorta by 2Dﬂow and by 4Dﬂow MRI acquisition blinding to the 2D results was per-formed.The agreement between 2D and 4D-ﬂow MRI was calculated as the intraclass correlation coefﬁcient(Icc).The mean absolute differences between 4D and 2Dﬂows were analyzed using linear regression models.Results:4D-ﬂow MRI acquisition time was slightly lower than 2D(7.6±1.8 min vs.9.4±3.3 min,p=0.03).Flow was slightly predominant in the right pulmonary artery(58%of total pulmonaryﬂow).conduit/tunnel-pul-monary arteriesﬂow accounted for 60%of the Fontan circuit.Agreement between 2D and 4D was overall good-to-excellent from Icc:0.81795%cI:0.637–0.907 to 0.93295%cI:0.866–0.965.There was no signiﬁcant inﬂu-ence of evaluated parameters on the agreement on 4D and 2Dﬂow.conclusions:4D-ﬂow MRI represents a valid tool in Fontan’sﬂow quantiﬁcation.Further larger studies are needed to conﬁrm our results and to evaluate the impact of advanced 4D-ﬂow MRI parameters on the prognostic stratiﬁcation in patients after Fontan palliation.

关键词： Fontan palliation fontanﬂows 4Dﬂow MRI 2Dﬂow MRI cardiac magnetic resonance

Kinetics of defect formation in chemically vapor deposited （cVD） graphene during laser irradiation： The case of Raman investigation

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Nano Research 2015年第12期8卷 3972-3981页

作者： Giampiero Amato gianluca Milano Umberto Vignolo Ettore Vittone Quantum Research Laboratory INRIM Strada delle Cacce 91 Torino Italy Department of Physics NIS Research Center University of Torino via Pietro Giuria 1 10125 Torino Italy

激光照耀在上的效果化学上，蒸汽扔了(cVD ) graphene 被分析在各种各样的照明条件下面获得的拉曼系列的时间的进化学习。系列证明缺点相关的山峰的规范的紧张与暴露时间的方形的根增加并且与激光力量密度几乎线性地变化。而且，到放射... 详细信息

激光照耀在上的效果化学上，蒸汽扔了(cVD ) graphene 被分析在各种各样的照明条件下面获得的拉曼系列的时间的进化学习。系列证明缺点相关的山峰的规范的紧张与暴露时间的方形的根增加并且与激光力量密度几乎线性地变化。而且，到放射损坏的 graphene 的坚硬取决于它的内在的结构的质量。结果建议与普通信仰相反， micro-Raman 光谱学不能为 graphene 的描述被认为一个 noninvasive 工具。试验性的观察与我们在 hydrogenated 从 StaeblerWronski 效果的解释途径导出的一个模型兼容非结晶的硅；这条途径假设 photoexcited 搬运人的再结合导致碎弱 cc 契约。

关键词：缺陷形成激光辐照化学气相沉积石墨动力学显微拉曼光谱激光功率密度氢化非晶硅