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In vitro angiogenesis in response to biomaterial properties for bone tissue engineering:a review of the state of the art

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Regenerative Biomaterials 2023年第1期10卷 744-783页

作者： Else Ellermann Nima meyer Ruth E.Cameron serena m.best Department of materials Science and metallurgy University of CambridgeCambridge CB30FSUK

Bone tissue engineering(BTE)aims to improve the healing of bone fractures using scaffolds that mimic the native extracellular *** successful bone regeneration,scaffolds should promote simultaneous bone tissue formation and blood vessel growth for nutrient and waste ***,a significant challenge in regenerative medicine remains the development of grafts that can be vascularized *** other things,optimization of physicochemical conditions of scaffolds is key to achieving appropriate angiogenesis in the period immediately following *** phosphates and collagen scaffolds are two of the most widely studied biomaterials for BTE,due to their close resemblance to inorganic and organic components of bone,respectively,and their bioactivity,tunable biodegradability and the ability to produce tailored *** various strategies exist to enhance vascularization of these scaffolds in vivo,further in vitro assessment is crucial to understand the relation between physicochemical properties of a biomaterial and its ability to induce *** mono-culture studies can provide evidence regarding cell-material interaction of a single cell type,a co-culture procedure is crucial for assessing the complex mechanisms involved in angiogenesis.A co-culture more closely resembles the natural tissue both physically and biologically by stimulating natural intercellular interactions and mimicking the organization of the in vivo ***,a co-culture is a complex system requiring optimization of various parameters including cell types,cell ratio,culture medium and seeding *** fundamental knowledge of the mechanism behind the bioactivity of biomaterials and understanding the contribution of surface and architectural features to the vascularization of scaffolds,and the biological response in general,can provide an invaluable basis for future optimization *** review gives an overview of the

关键词： angiogenesis collagen scaffolds hydroxyapatite co-culture architectural features physicochemical properties

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Adjusting the physico-chemical properties of collagen scaffolds to accommodate primary osteoblasts and endothelial cells

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Regenerative Biomaterials 2023年第1期10卷 590-602页

作者： Nima meyer Daniel V.Bax Jochen Beck Ruth E.Cameron serena m.best Department of materials Science and metallurgy University of CambridgeCambridge CB30FSUK Geistlich Pharma AG Product DevelopmentWolhusenSwitzerland

Collagen-based biomaterials are used widely as tissue engineering scaffolds because of their excellent bioactivity and their similarity to the natural *** regeneration of healthy bone tissue requires simultaneous support for both osteoblasts and,where angiogenesis is intended,endothelial *** it is important to tailor carefully the biochemical and structural characteristics of the scaffold to suit the needs of each cell *** work describes for the first time a systematic study to gain insight into the cell type-specific response of primary human osteoblast(hOBs)and human dermal microvascular endothelial cells(HDmECs)to insoluble collagen-based *** behaviour was evaluated on both 2D films and 3D scaffolds,produced using *** collagen was cross-linked at various EDC/NHS concentrations and mono-cultured with hOBs and HDmECs to assess the effect of architectural features and scaffold stabilization on cell *** was observed that 3D scaffolds cross-linked at 30%of the standard conditions in literature offered an optimal combination of mechanical stiffness and cellular response for both cell types,although endothelial cells were more sensitive to the degree of cross-linking than *** features have a time-dependent impact on the cell migration profile,with alignment being the most influential parameter overall.

关键词： angiogenesis collagen scaffolds cell migration EDC/NHS cross-linking

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Avoiding artefacts in microCT imaging of collagen scaffolds:Effect of phosphotungstic acid(PTA)-staining and crosslink density

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Bioactive materials 2022年第2期7卷 210-219页

作者： Kyung-Ah Kwon Daniel V.Bax Jennifer H.Shepherd Ruth E.Cameron serena m.best Cambridge Centre for medical materials Department of Materials Science and MetallurgyUniversity of CambridgeCambridgeUnited Kingdom School of Engineering University of LeicesterLeicesterUnited Kingdom

X-ray micro-computed tomography(μ-CT)can be used to provide both qualitative and quantitative information on the structure of three-dimensional(3D)bioactive *** performed in a dry state,μ-CT accurately reflects the structure of collagen-based scaffolds,but imaging in a wet state offers challenges with *** we have used phosphotungstic acid(PTA)as a contrast agent to visualise fully hydrated collagen scaffolds in a physiologically relevant environment.A systematic investigation was performed to understand the effects of PTA on the results of μ-CT imaging by varying sample processing variables such as crosslinking density,hydration medium and staining *** samples in 0.3% PTA solution overnight completely stained the samples and the treatment provided a successful route forμ-CT analysis of crosslinked ***,significant structural artefacts were observed for samples which were either non-crosslinked or had low levels of crosslinking,which had a heterogeneous interior architecture with collapsed pores at the scaffold *** work highlights the importance of optimising the choice of processing and staining conditions to ensure accurate visualisation for hydrated 3D collagen scaffolds in an aqueous medium.

关键词： microCT crosslinking qualitative

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Targeted protein delivery:carbodiimide crosslinking influences protein release from microparticles incorporated within collagen scaffolds

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Regenerative Biomaterials 2019年第5期6卷 279-287页

作者： Constantin Edi Tanase Omar Qutachi Lisa J.White Kevin m.Shakesheff Andrew W.mcCaskie serena m.best Ruth E.Cameron Department of materials Science and metallurgy University of CambridgeCambridge Centre for Medical MaterialsCambridge27Charles Babbage RoadCB30FSUK Centre for Biomolecular Sciences School of PharmacyUniversity of NottinghamUniversity ParkNottingham NG72RDUK Division of Trauma&Orthopaedic Surgery Department of SurgeryUniversity of CambridgeBox 180Addenbrooke’s HospitalHills RoadCambridge CB20QQUK Present address:School of Pharmacy De Montforte UniversityLeicester LE19BHUK

Tissue engineering response may be tailored via controlled,sustained release of active agents from protein-loaded degradable microparticles incorporated directly within three-dimensional(3D)ice-templated collagen ***,the effects of covalent crosslinking during scaffold preparation on the availability and release of protein from the incorporated microparticles have not been ***,we load 3D ice-templated collagen scaffolds with controlled additions of poly-(DL-lactide-co-glycolide)*** probe the effects of subsequent N-(3-dimethylaminopropyl)-N0-ethylcarbodiimide hydrochloride crosslinking on protein release,using microparticles with different internal protein *** isothiocyanate labelled bovine serum albumin is used as a model protein *** scaffolds display a homogeneous microparticle distribution,and a reduction in pore size and percolation diameter with increased microparticle addition,although these values did not fall below those reported as necessary for cell *** protein distribution within the microparticles,near the surface or more deeply located within the microparticles,was important in determining the release profile and effect of crosslinking,as the surface was affected by the carbodiimide crosslinking reaction applied to the *** of microparticles with a high proportion of protein at the surface caused both a reduction and delay in protein *** located within the bulk of the microparticles,was protected from the crosslinking reaction and no delay in the overall release profile was seen.

关键词： collagen scaffolds PLGA microparticles FITC-BSA EDC crosslinking pore size percolation diameter

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Effect of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide concentrations on the mechanical and biological characteristics of cross-linked collagen fibres for tendon repair

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Regenerative Biomaterials 2015年第2期2卷 77-85页

作者： Zafar Ahmad Jennifer H.Shepherd David V.Shepherd Siddhartha Ghose Simon J.Kew Ruth E.Cameron serena m.best Roger A.Brooks John Wardale Neil Rushton Orthopaedic Research Unit Department of Surgery University of CambridgeAddenbrooke’s HospitalCambridgeCB20QQUK Department of materials Science and metallurgy University of CambridgeCambridgeCB30FSUK Tigenix Ltd CambridgeCB40FYUK

Reconstituted type I collagen fibres have received considerable interest as tendon implant materials due to their chemical and structural similarity to the native *** produced through a semi-continuous extrusion process were cross-linked with different concentrations of the zerolength cross-linker 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide(EDC)in combination with N-hydroxysuccinimide(NHS).Tensile properties of the fibres were considered,along with imaging of both surface structure and fibrillar *** of the fibres to bacterial collagenase was investigated and fibre sections seeded with human tendon cells for biological characterization,including cell adhesion and *** work clearly demonstrated that whilst the concentration of EDC and NHS had no significant effect on the mechanics,a higher concentration was associated with higher collagenase resistance,but also provided a less attractive surface for cell adhesion and proliferation.A lower cross-linking concentration offered a more biocompatible material without reduction in mechanics and with a potentially more optimal degradability.

关键词： biopolymer scaffolds soft tissue

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Vitamin C as a promoter of γδ T cells

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Cellular & molecular Immunology 2021年第2期18卷 510-512页

作者： serena meraviglia Francesco Dieli Central Laboratory of Advanced Diagnosis and Biomedical Research(CLADIBIOR) University of PalermoPalermoItaly Department of Biomedicine Neurosciences and Advanced DiagnosisUniversity of PalermoPalermoItaly

HumanγδT cells are a small CD3+subset exhibiting features of both innate and adaptive immune cell.1 The majorγδT cell population in peripheral blood expresses the Vγ9 and Vδ2 chains and recognizes phosphoantigens(PAgs)that are overexpressed by tumor cells in the absence of genetic *** and expansion of Vγ9Vδ2 T cells is also achieved by aminobisphosphonates(n-BPs),which promote the intracellular accumulation of *** of their potent cytotoxic and antitumor activity,Vγ9Vδ2 T cells are particularly indicated for use in cancer immunotherapy,even against tumors with low mutational burdens.

关键词： γδT chains absence

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Lesion-symptom mapping with NIHSS sub-scores in ischemic stroke patients

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Stroke & Vascular Neurology 2022年第2期7卷 124-131页

作者： Deepthi Rajashekar matthias Wilms m Ethan macDonald serena Schimert michael D Hill Andrew Demchuk mayank Goyal Sean P Dukelow Nils Daniel Forkert Biomedical Engineering Graduate Program Hotchkiss Brain InstituteUniversity of CalgaryCalgaryAlbertaCanada Department of Radiology Cumming School of MedicineUniversity of CalgaryCalgaryAlbertaCanada Hotchkiss Brain Institute University of CalgaryCalgaryAlbertaCanada Department of Clinical Neurosciences University of CalgaryCalgaryAlbertaCanada Department of Electrical and Computer Engineering University of CalgaryCalgaryAlbertaCanada Department of Community Health Sciences Cumming School of MedicineUniversity of CalgaryCalgaryAlbertaCanada Department of medicine Cumming School of MedicineUniversity of CalgaryCalgaryAlbertaCanada Alberta Children's Hospital Research Institute University of CalgaryCalgaryABCanada

Background Lesion-symptom mapping(LSm)is a statistical technique to investigate the population-specific relationship between structural integrity and post-stroke clinical *** clinical practice,patients are commonly evaluated using the National Institutes of Health Stroke Scale(NIHSS),an 11-domain clinical score to quantitate neurological deficits due to *** far,LSm studies have mostly used the total NIHSS score for analysis,which might not uncover subtle structure–function relationships associated with the specific sub-domains of the NIHSS ***,the aim of this work was to investigate the feasibility to perform LSm analyses with sub-score information to reveal category-specific structure–function relationships that a total score may not *** Employing a multivariate technique,LSm analyses were conducted using a sample of 180 patients with NIHSS assessment at 48-hour post-stroke from the ESCAPE *** NIHSS domains were grouped into six categories using two *** was conducted for each category of the two groupings and the total NIHSS *** Sub-score LSms not only identify most of the brain regions that are identified as critical by the total NIHSS score but also reveal additional brain regions critical to each function category of the NIHSS assessment without requiring extensive,specialised *** These findings show that widely available sub-scores of clinical outcome assessments can be used to investigate more specific structure–function relationships,which may improve predictive modelling of stroke outcomes in the context of modern clinical stroke assessments and neuroimaging.

关键词： patients score category

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High risk of temporomandibular disorder in irritable bowel syndrome: Is there a correlation with greater illness severity?

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World Journal of Gastroenterology 2017年第1期23卷 103-109页

作者： serena Gallotta Vincenzo Bruno Santo Catapano Nicola mobilio Carolina Ciacci Paola Iovino Functional GI Disorders Center at Gastrointestinal Unit AOU S. Giovanni di Dio e Ruggi d’Aragona Department of Medicine and Surgery University of Salerno Dental School University of Ferrara

AImTo investigate the prevalence and the risk of temporomandibular disorders (TmDs) in patients with irritable bowel syndrome (IBS) (including each subtype: constipation, diarrhoea, and mixed) compared to the general *** January 2014 and December 2015 we enrolled consecutively adult patients diagnosed with IBS at the outpatient clinic of the University of Salerno and healthy controls (HC) without IBS. At enrollment, we analyzed all patients for the presence of TmDs according to the Research Diagnostic Criteria for *** enrolled 91 IBS patients (23 IBS-D, 30 IBS-C and 38 IBS-m) and 57 HC in the study. We found a higher risk of having TmD (OR = 3.41, 95%CI: 1.66-7.01) compared to the HC. The risk of having TmD was independent of IBS-subtype. multiple regression analysis showed that facial pain was positively related to abdominal pain and higher level of *** patients had a more than three times greater risk of TmD compared to HC. The risk of having TmD was similar in different IBS subtypes. IBS patients that also fulfilled criteria for TmD seem to share along with chronic facial and abdominal pain a significant co-occurrence with psychiatric disorders and female preponderance.

关键词： Temporomandibular disorders Irritable bowel syndrome Chronic pain Facial pain Abdominal pain Irritable bowel syndrome severity score symptoms Irritable bowel syndrome predominant diarrhea Irritable bowel syndrome predominant constipation Irritable bowel syndrome mixed

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New endoscopy advances to refine adenoma detection rate for colorectal cancer screening:None is the winner

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World Journal of Gastrointestinal Oncology 2017年第10期9卷 402-406页

作者： marcello maida Salvatore Camilleri michele manganaro serena Garufi Giuseppe Scarpulla Section of Gastroenterology S.Elia-M.Raimondi Hospital93100 CaltanissettaItaly

Colorectal cancer(CRC) is the third most common cancer in males and second in females, and globally the fourth cause for cancer death worldwide. Oncological screening of CRC has a major role in the management of the disease and it is mostly performed by colonoscopy. Anyway, effectiveness of endoscopic screening for CRC strictly depends on adequate detection and removal of potentially precancerous lesions, and accuracy of colonoscopy in detection of adenomas is still suboptimal. For this reason, several technological advances have been implemented in order to improve the diagnostic sensitivity of colonoscopy in adenoma detection. Among these:(1) Visual technologies such as chromoendoscopy and narrow band imaging;(2) optical innovation as high definition endoscopy, full-spectrum endoscopy or Third Eye Retroscope; and(3) mechanical advances as Cap assisted colonoscopy, Endocuff, Endoring and G-Eye endoscope. All these technologies advances have been tested over time by clinical studies with mixed results. Which of them is more likely to be successful in the next future?

关键词： Colorectal cancer screening Colonoscopy Adenoma detection rate Diagnostic advances

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Current and future applications of magnetic resonance imaging and spectroscopy of the brain in hepatic encepha-lopathy

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World Journal of Gastroenterology 2006年第19期12卷 2969-2978页

作者： VP Bob Graver m Alex Dresner Daniel m Forton serena Counsell David J Larkman Nayna Patel Howard C Thomas Simon D Taylor-Robinson Hepatology Section Division of medicine A St Mary's CampusFaculty of MedicineImperial College LondonSouth Wharf StreetLondon W2 1NYUnited Kingdom Imaging Sciences DepartmentClinical Sciences DivisionFaculty of MedicineImperial College LondonHammersmith HospitalDu Cane RoadLondon W12 0HSUnited Kingdom Imaging Sciences Department Clinical Sciences Division Faculty of MedicineImperial College LondonHammersmith HospitalDu Cane RoadLondon W12 0HSUnited Kingdom Hepatology Section Division of medicine A St Mary's CampusFaculty of MedicineImperial College LondonSouth Wharf StreetLondon W2 1NYUnited Kingdom

Hepatic encephalopathy （HE） is a common neuropsychiatric abnormality, which complicates the course of patients with liver disease and results from hepatocellular failure and/or portosystemic shunting. The manifestations of HE are widely variable and involve a spectrum from mild subclinical disturbance to deep coma. Research interest has focused on the role of circulating gut-derived toxins, particularly ammonia, the development of brain swelling and changes in cerebral neurotransmitter systems that lead to global CNS depression and disordered function. Until recently the direct investigation of cerebral function has been difficult in man. However, new magnetic resonance imaging （mRI） techniques provide a non-invasive means of assessment of changes in brain volume （coregistered mRI） and impaired brain function （fmRI）, while proton magnetic resonance spectroscopy （^1H mRS） detects changes in brain biochemistry, including direct measurement of cerebral osmolytes, such as myoinositol, glutamate and glutamine which govern processes intrinsic to cellular homeostasis, including the accumulation of intracellular water. The concentrations of these intracellular osmolytes alter with hyperammonaemia. mRS-detected metabolite abnormalities correlate with the severity of neuropsychiatric impairment and since mR spectra return towards normal after treatment, the technique may be of use in objective patient monitoring and in assessing the effectiveness of various treatment regimens.

关键词： Hepatic encephalopathy magnetic resonance imaging magnetic resonance spectroscopy Diffusion weighted imaging Arterial spin labeling Functional mRI

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