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Nanoscale viscoelastic properties and adhesion of polydimethylsiloxane for tissue engineering

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Acta Mechanica Sinica 2014年第1期30卷 2-6页

作者： J.Chen K.E.Wright M.A.Birch School of Mechanical & Systems Engineering Newcastle University arthritis research uk (ARuk) Tissue Engineering centre Institute of Cellular MedicineNewcastle UniversityUK research uk (ARuk) Tissue Engineering centre Institute of Cellular MedicineNewcastle UniversityUK St James’ University Hospital University of Leeds UK

It has shown that altering crosslink density of biopolymers will regulate the morphology of Mesenchymal Stem Cells （MSCs） and the subsequent MSCs differentia- tion. These observations have been found in a wide range of biopolymers. However, a recent work published in Nature Materials has revealed that MSCs morphology and differen- tiation was unaffected by crosslink density of polydimethyl- siloxane （PDMS）, which remains elusive. To understand such unusual behaviour, we use nanoindentation tests and modelling to characterize viscoelastic properties and sur- face adhesion of PDMS with different base：crosslink ratio varied from 50：1 （50D） to 10：1 （10D）. It has shown that lower crosslink density leads to lower elastic moduli. De- spite lower nanoindentation elastic moduli, PDMS with lowest crosslink density has higher local surface adhesion which would affect cell-biomaterials interactions. This work suggests that surface adhesion is likely another important physical cue to regulate cell-biomaterials interactions.

关键词： Bioploymer- Nanoindentation- Viscoelasticity Surface adhesion

Dehydroepiandrosterone:a potential therapeutic agent in the treatment and rehabilitation of the traumatically injured patient

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Burns & Trauma 2019年第1期7卷 248-260页

作者： Conor Bentley Jon Hazeldine Carolyn Greig Janet Lord Mark Foster NIHR Surgical Reconstruction and Microbiology research centre University Hospital BirminghamBirmingham B152WBUK School of Sport Exercise and Rehabilitation SciencesUniversity of BirminghamBirminghamUK MRC-arthritis research uk centre for Musculoskeletal Ageing research Institute of Inflammation and AgeingBirmingham University Medical SchoolBirmingham B152TTUK NIHR Biomedical research centre University Hospital BirminghamBirminghamUK Royal centre for Defence Medicine Birmingham Research ParkBirmingham B152SQUK.

Severe injuries are the major cause of death in those aged under 40,mainly due to road traffic ***,metabolic and immune pathways respond to limit the tissue damage sustained and initiate wound healing,repair and regeneration ***,depending on age and sex,the response to injury and patient prognosis differ *** are catabolic and immunosuppressive and are produced as part of the stress response to injury leading to an intra-adrenal shift in steroid biosynthesis at the expense of the anabolic and immune enhancing steroid hormone dehydroepiandrosterone(DHEA)and its sulphated metabolite dehydroepiandrosterone sulphate(DHEAS).The balance of these steroids after injury appears to influence outcomes in injured humans,with high cortisol:DHEAS ratio associated with increased morbidity and *** models of trauma,sepsis,wound healing,neuroprotection and burns have all shown a reduction in proinflammatory cytokines,improved survival and increased resistance to pathological challenges with DHEA *** supplementation studies,which have focused on post-menopausal females,older adults,or adrenal insufficiency have shown that restoring the cortisol:DHEAS ratio improves wound healing,mood,bone remodelling and psychological ***,there are no DHEA or DHEAS supplementation studies in trauma patients,but we review here the evidence for this potential therapeutic agent in the treatment and rehabilitation of the severely injured patient.

关键词： Dehydroepiandrosterone Dehydroepiandrosterone sulphate Traumatic injury Intensive care Immune Rehabilitation

The minor collagens in articular cartilage

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Protein & Cell 2017年第8期8卷 560-572页

作者： Yunyun Luo DovUe Sinkeviciute Yi He Morten Karsdal Yves Henrotin Ali Mobasheri Patrik Onnerfjord Anne Bay-Jensen Biomarkers & research Nordic Bioscience A/S Herlev Denmark Faculty of Healthy and Medical Sciences University of Copenhagen Copenhagen Denmark Department of Clinical Sciences Medical Faculty Lund University Lund Sweden Bone and Cartilage research Unit Institute of Pathology Level 5 Arthropole Liege University of Liege CHU Sart-Tilman4000 Liege Belgium Faculty of Health and Medical Sciences University of Surrey Guildford Surrey GU2 7XH UK arthritis research uk centre for Sport Exercise and Osteoarthritis Arthritis Research UK Centre for Musculoskeletal AgeingResearch Queen's Medical Centre Nottingham NG7 2UH UK

Articular cartilage is a connective tissue consisting of a specialized extracellular matrix （ECM） that dominates the bulk of its wet and dry weight. Type Ⅱ collagen and aggrecan are the main ECM proteins in cartilage. However, little attention has been paid to less abundant molecular components, especially minor collagens, including type Ⅳ, Ⅵ, Ⅸ, Ⅹ, Ⅺ, Ⅻ, ⅩⅢ, and ⅩⅣ, etc. Although accounting for only a small fraction of the mature matrix, these minor collagens not only play essential structural roles in the mechanical properties, organization, and shape of articular cartilage, but also fulfil specific biological functions. Genetic studies of these minor collagens have revealed that they are associated with multiple connective tissue diseases, especially degenerative joint disease. The progressive destruction of cartilage involves the degradation of matrix constituents including these minor collagens. The generation and release of fragmented molecules could generate novel biochemical markers with the capacity to monitor disease progression, facilitate drug development and add to the existing toolbox for in vitro studies, preclinical research and clinical trials.

关键词： collagen biomarker arthritis

Neuropathic pain-like symptoms and pre-surgery radiographic severity contribute to patient satisfaction 4.8 years post-total joint replacement

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World Journal of Orthopedics 2017年第10期8卷 761-769页

作者： Sophie C Warner Helen Richardson Wendy Jenkins Thomas Kurien Michael Doherty Ana M Valdes Academic Rheumatology University of NottinghamClinical Sciences BuildingNottingham City Hospital Department of Cardiovascular Sciences University of Leicester and National Institute for Health Res-earchLeicester Cardiovascular Biomedical Research Unit arthritis research uk pain centre Academic Division of Trauma and Orthopaedics Queens Medical Centre

AIM To investigate a comprehensive range of factors that contribute to long-term patient satisfaction post-total joint replacement(TJR) in people who had undergone knee or hip replacement for *** Participants(n = 1151) were recruited from Nottinghamshire post-total hip or knee replacement. Questionnaire assessment included medication use, the pain-DETECT questionnaire(PDQ) to assess neuropathic pain-like symptoms(NP) and TJR satisfaction measured on average 4.8 years post-TJR. Individual factors were tested for an association with post-TJR satisfaction, before incorporating all factors into a full model. Data reduction was carried out using LASSO and receiveroperator characteristic(ROC) curve analysis was used to quantify the contribution of variables to post-TJR *** After data reduction, the best fitting model for post-TJR satisfaction included various measures of pain, history of revision surgery, smoking, pre-surgical X-ray severity, WOMAC function scores and various comorbidities. ROC analysis of this model gave AUC = 0.83(95%CI: 0.80-0.85). PDQ scores were found to capture much of the variation in post-TJR satisfaction outcomes: AUC = 0.79(0.75-0.82). Pre-surgical radiographic severity was associated with higher post-TJR satisfaction: OR_(satisfied) = 2.06(95%CI: 1.15-3.69), P = *** These results highlight the importance of pre-surgical radiographic severity, post-TJR function, analgesic medication use and NP in terms of post-TJR satisfaction. The PDQ appears to be a useful tool in capturing factors that contribute to post-TJR satisfaction.

关键词： Osteoarthritis Patient satisfaction Total joint arthroplasty Neuropathic pain Surgery outcomes

Adiponectin signalling in bone homeostasis,with age and in disease

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Bone research 2021年第1期9卷 15-25页

作者： Jonathan W.Lewis James R.Edwards Amy J.Naylor Helen M.McGettrick Rheumatology research Group Institute of Inflammation and AgeingUniversity of BirminghamBirmingham B152TTUK Ageing&Regeneration research Group Botnar Research CentreUniversity of OxfordOxford OX37LDUK

Adiponectin is the most abundant circulating adipokine and is primarily involved in glucose metabolism and insulin *** the bone,osteoblasts and osteoclasts express the adiponectin receptors,however,there are conflicting reports on the effects of adiponectin on bone formation and *** studies have shown a pro-osteogenic role for adiponectin in in vivo murine models and in vitro:with increased osteoblast differentiation and activity,alongside lower levels of ***,human studies often demonstrate an inverse relationship between adiponectin concentration and bone ***,the presence of multiple isoforms of adiponectin and multiple receptor subtypes has the potential to lead to more complex signalling and functional *** such,we still do not fully understand the importance of the adiponectin signalling pathway in regulating bone homeostasis and repair in health,with age and in *** this review,we explore our current understanding of adiponectin bioactivity in the bone;the significance of its different isoforms;and how adiponectin biology is altered in ***,furthering our understanding of adiponectin regulation of bone biology is key to developing pharmacological and non-pharmacological(lifestyle)interventions that target adiponectin signalling to boost bone growth and repair in healthy ageing,following injury or in disease.

关键词： homeostasis metabolism consequences

Vitamin D receptor expression in human bone tissue and dose-dependent activation in resorbing osteoclasts

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Bone research 2016年第3期4卷 164-173页

作者： Allahdad Zarei Alireza Morovat Kassim Javaid Cameron P Brown Botnar research centre Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Science University of Oxford Oxford UK Clinical Biochemistry Oxford University Hospitals NHS Trust Oxford UK

The effects of vitamin D on osteoblast mineralization are well documented. Reports of the effects of vitamin D on osteoclasts, however, are conflicting, showing both inhibition and stimulation. Finding that resorbing osteoclasts in human bone express vitamin D receptor （VDR）, we examined their response to different concentrations of 25-hydroxy vitamin D3 [25（OH）D3] （100 or 500 nmol·L^-1） and 1,25-dihydroxy vitamin D3 [1,25（OH）2D3] （0.1 or 0.5 nmol·L^-1） metabolites in cell cultures. Specifically, CD14＋ monocytes were cultured in charcoal-stripped serum in the presence of receptor activator of nuclear factor kappa-B ligand （RANKL） and macrophage colony-stimulating factor （M-CSF）. Tartrate-resistant acid phosphatase （TRAP） histochemical staining assays and dentine resorption analysis were used to identify the size and number of osteoclast cells, number of nuclei per cell and resorption activity. The expression of VDR was detected in human bone tissue （ex vivo） by immunohistochemistry and in vitro cell cultures by western blotting. Quantitative reverse transcription-PCR （qRT-PCR） was used to determine the level of expression of vitamin D-related genes in response to vitamin D metabolites. VDR-related genes during osteoclastogenesis, shown by qRT-PCR, was stimulated in response to 500 nmol·L^-1 of 25（OH）D3 and 0.1-0.5 nmol·L^-1 of 1,25（OH）2D3, upregulating cytochrome P450 family 27 subfamily B member I （CYP27B1） and cytochrome P450 family 24 subfamily A member I （CYP24A1）. Osteoclast fusion transcripts transmembrane 7 subfamily member 4 （tm7sf4） and nuclear factor of activated T-cell cytoplasmic 1 （nfatcl） where downregulated in response to vitamin D metabolites. Osteoclast number and resorption activity were also increased. Both 25（OH）D3 and 1,25（OH）2D3 reduced osteoclast size and number when co-treated with RANKL and M-CSF. The evidence for VDR expression in resorbing osteoclasts in vivo and low-dose effects of 1,25（OH）2D3 on osteoclasts in vitro may therefore provide

关键词： Vitamin D receptor expression in human bone tissue and dose-dependent activation in resorbing osteoclasts bone

Meta-Analysis of Clinical Outcomes of Lumbar Fusion Surgical Interventions for Degenerative Spondylolisthesis

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International Journal of Clinical Medicine 2018年第7期9卷 590-599页

作者： Khaled Aneiba Sabri Garoushi Mohammed Elmajee Mohamed Elsllabi Osama A. Tashani University Hospital of North Tees Stockton-on-Tees UK centre for pain research Leeds Beckett University Leeds UK The Royal Oldham Hospital Oldham UK Barnsley District Hospital Barnsley UK

Introduction: Surgical interventions for degenerative spondylolisthesis are varied with comparable claims of success. Fusion based technique is one of the most commonly used surgical interventions in treating this condition. The aim of this meta-analysis is to compare the effectiveness of the Lumbar Interbody Fusion techniques (specifically Posterolateral Interbody approach—PLIF) versus Posterolateral Instrumented Fusion (PLF). The clinical outcomes investigated were: back pain, leg pain, function, Oswestery Disability Index (ODI), Disability Rating Index (DRI), fusion and revision rates if reported. Methods: Combinations of keywords and MeSH terms, where appropriate, were used to search for studies in Medline via Ovid, Embase, Cochrane Library, and Google scholar. The initial search was conducted on 10 August 2016 and updated on 13 June 2017. Eligibility criteria for the studies to be selected for this meta-analysis were: Randomised Controlled Trials (RCTs), cohort and consecutive cases studies that compared at PLIF versus PLF surgical interventions at the lumbar region. Heterogeneity indicators and Forest plot were computed using RevMan 5. Results: Out of the initial hits of 3021, 5 articles were selected as relevant and assessed for risk of bias and then data was extracted and tabulated. These 5 studies reported data from (900 patients’ records, follow up ranges from 6 months to 5 years) undergone one of 2 interventions (PLIF or PLF). The overall effect for ODI and leg pain showed no advantage of any intervention over the other while there was a greater odd ratio of fusion if the operation applied PLIF techniques (Overall Z = 2.86, p = 0.004). Conclusions: There is a need for more high quality clinical trials to compare these two interventions. However, available data indicate that there are comparable results in the main clinical outcomes between PLIF and PLF. PLIF has superior fusion rate which does not seem to affect post-operative pain ratings.

关键词： PLIF PLF Lumbar Spine pain Spondylolisthesis Fusion Techniques Review

Metabolomic and proteomic applications to exercise biomedicine

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Translational Exercise Biomedicine

Translational Exercise Biomedicine 2024年第1期1卷 9-22页

作者： Daniel J.Wilkinson Hannah Crossland Philip J.Atherton centre of Metabolism Ageing&Physiology(CoMAP)Medical Research Council/Versus Arthritis UK Centre of Excellence for Musculoskeletal Ageing Research(CMAR)School of MedicineUniversity of NottinghamRoyal Derby HospitalUttoxeter RoadDerbyDE223DTUK

Objectives:‘OMICs encapsulates study of scaled data acquisition,at the levels of DNA,RNA,protein,and metabolite *** broad objectives of OMICs in biomedical exercise research are multifarious,but commonly relate to biomarker development and understanding features of exercise adaptation in health,ageing and metabolic ***:Thisﬁeld is one of exponential technical(i.e.,depth of feature coverage)and scientiﬁc(i.e.,in health,metabolic conditions and ageing,multi-OMICs)progress adopting targeted and untargeted ***:Keyﬁndings in exercise biomedicine have led to the identiﬁcationofOMIC featureslinking toheritability or adaptive responses to exercise e.g.,the forging of GWAS/proteome/metabolome links to cardiovascularﬁtness and metabolic health *** recent addition of stable isotope tracing to proteomics(‘dynamic proteomics’)and metabolomics(‘ﬂuxomics’)represents the next phase of state-of-the-art in‘***:These methods overcome limitations associated with point-in-time‘OMICs and can be achieved using substrate-speciﬁc tracers or deuterium oxide(D2O),depending on the question;these methods could help identify how individual protein turnover and metaboliteﬂux may explain exercise *** contend application of these methods will shed new light in translational exercise biomedicine.

关键词： OMICs stable isotope tracers exercise muscle

A systematic review of patient reported outcome measures (PROMs) and quality of life reporting in patients undergoing laparoscopic cholecystectomy

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Hepatobiliary Surgery and Nutrition 2019年第3期8卷 228-245页

作者： Prita Daliya Elizabeth H.Gemmill Dileep N.Lobo Simon L.Parsons Gastrointestinal Surgery Nottingham Digestive Diseases Centre and National Institute for Health Research(NIHR)Nottingham Biomedical Research CentreNottingham University Hospitals NHS Trust and University of NottinghamQueen’s Medical CentreNottingham NG72UHUK Department of General Surgery Sherwood Forest Hospitals NHS TrustKing’s Mill HospitalSutton-in-Ashfield NG174JLUK MRC/ARuk centre for Musculoskeletal Ageing research School of Life SciencesUniversity of NottinghamQueen’s Medical CentreNottingham NG72UKUK Trent Oesophago-Gastric Unit City Hospital CampusNottingham University Hospitals NHS TrustNottingham NG51PBUK

Patient reported outcome measures(PROMs)provide a valuable means of measuring outcomes subjectively from a patient's perspective,facilitating the assessment of service quality across healthcare providers,and assisting patients and clinicians in shared decision *** primary aim of this systematic review was to critically appraise all historic studies evaluating patient reported quality of life,in adult patients undergoing laparoscopic cholecystectomy for symptomatic *** secondary aim was to perform a quality assessment of cholecystectomy-specific PROM-validation studies.A literature review was performed in PubMed,Google ScholarTM,the Cochrane Library,Medline,CINAHL,EMBASE and PsychINFO databases up to September *** characteristics,PROM-specific details and a bias assessment were summarised for non-validation studies.A COnsensus-based Standards for the selection of health Measurement INstruments(COSMIN)analysis was performed to assess the methodological quality of identified PROM-validation *** one studies were found to evaluate health-related quality of life(HRQoL)after laparoscopic *** 94.1%of these studies included PROMs as a primary outcome measure,<20%provided level 1 evidence through randomised controlled trials(RCTs).There was significant variation in the selection and reporting of PROMs,with no studies declaring patient involvement in PROM selection,and 88.2%of studies failing to document the management of missing data points,or non-returned surveys(33.3%).In the 6 PROM-validation studies identified,only 5 psychometric properties were evaluated,the findings of which were limited due to the small number of *** systematic review identifies a lack in consistency of study design and PRO reporting in clinical *** an increasing number of studies are being performed to evaluate PROs,a lack of adherence to existing PRO administration and reporting guidelines is continuing to negatively affect st

关键词： Cholecystectomy patient reported outcomes(PROs) patient reported outcome measures(PROMs) quality of life(QoL) COnsensus-based Standards for the selection of health Measurement INstruments(COSMIN)