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Engineering nanoparticles for targeting rheumatoid arthritis： Past, present, and future trends

Nano Research 2018年第9期11卷 4489-4506页

作者： Isabel Matos oliveira Cristiana Goncalves Rui Lufs Reis joaquim miguel oliveira B's Research Group - Biomatefials Biodegradables and Biomimetics Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine AvePark 4805-017 Barco Guimaraes Portugal ICVS/3B's-PTGovernment Associate Laboratory University of Minho Campus de Gualtar 4710-057 Braga Portugal The Discoveries Centre for Regenerative and Precision Medicine Headquarters at University of Minho Avepark 4805-017 Barco Guimaraes Portugal

Rheumatoid arthritis （RA） is a chronic inflammatory disease characterized by synovial joint inflammation and cartilage and bone tissue destruction. Although there exist some treatment strategies for RA, they are not completely safe and effective. Therefore, it is important to develop and test new drugs for RA that specifically target inflamed/swollen joints and simultaneously attenuate other possible damages to healthy tissues. Nanotechnology can be a good alternative to consider when envisioning predse medication for treating RA. Through the use of nanopartides, it is possible to increase bioavailability and bioactivity of therapeutics and enable selective targeting to damaged joints. Herein, recent studies using nanoparticles for the treatment of RA, namely with liposomes, polymeric nanoparticles, dendrimers, and metallic nanoparticles, have been reviewed. These therapeutic strategies have shown great promise in improving the treatment over that by traditional drugs. The results of these studies confirm that feasibility of the use of nanopartides is mainly due to their biocompatibility, low toxicity, controlled release, and selective drug delivery to inflamed tissues in animal RA models. Therefore, it is possible to claim that nanotechnology will, in the near future, play a crucial role in advanced treatments and patient-specific therapies for human diseases such as RA.

关键词： nanoparticles liposomes dendrimers rheumatoid arthritis

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Current advances in solid free-form techniques for osteochondral tissue engineering

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Bio-Design and Manufacturing 2018年第3期1卷 171-181页

作者： Joao Bebiano Costa Joana Silva-Correia Rui Luis Reis joaquim miguel oliveira B's Research Group I3Bs - Research Institute onBiomaterials Biodegradables and Biomimetics University ofMinho Headquarters of the European Institute of Excellenceon Tissue Engineering and Regenerative Medicine AveParkParque de Ciencia e Tecnologia Zona Industrial da Gandra4805-017 Barco Guimaraes Portugal ICVS/3B's-PT Government Associate Laboratory Braga Guimarfies Portugal The Discoveries Centre for Regenerative and PrecisionMedicine Headquarters at University of MinhoAvepark 4805-017 Barco Guimaraes Portugal

Osteochondral （OC） lesions are characterized by defects in two different zones, the cartilage region and subchondral bone region. These lesions are frequently associated with mechanical instability, as well as osteoarthritic degenerative changes in the knee. The lack of spontaneous healing and the drawbacks of the current treatments have increased the attention from the scientific community to this issue. Different tissue engineering approaches have been attempted using different polymers and different scaffolds＇ processing. However, the current conventional techniques do not allow the full control over scaffold fabrication, and in this type of approaches, the tuning ability is the key to success in tissue regeneration. In this sense, the researchers have placed their efforts in the development of solid free-form （SFF） techniques. These techniques allow tuning different properties at the micro-macro scale, creating scaffolds with appropriate features for OC tissue engineering. In this review, it is discussed the current SFF techniques used in OC tissue engineering and presented their promising results and current challenges.

关键词： Solid free-form Osteochondral Tissue engineering Scaffolds

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Properties of Collagen/Sodium Alginate Hydrogels for Bioprinting of Skin Models

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Journal of Bionic Engineering 2023年第1期20卷 105-118页

作者： Tian Jiao Qin Lian Weilong Lian Yonghui Wang Dichen Li Rui L.Reis joaquim miguel oliveira State Key Laboratory for Manufacturing System Engineering Xi’an Jiaotong UniversityXi’an710049China Shaanxi Ketao-AM Technology Co. Ltd.Xi’an710100China B’s Research Group I3Bs—Research Institute on BiomaterialsBiodegradables and BiomimeticsHeadquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineUniversity of MinhoBarco4805-017GuimarãesPortugal ICVS/3B’s–PT Government Associate Laboratory Barco4805-017GuimarãesPortugal

3D printing technology has great potential for the reconstruction of human ***,the reconstructed skin has some differences from natural skin,largely because the hydrogel used does not have the appropriate biological and physical properties to allow healing and *** study examines the swelling,degradability,microstructure and biological properties of Collagen/Sodium Alginate(Col/SA)hydrogels of differing compositions for the purposes of skin *** the content of sodium alginate causes the hydrogel to exhibit stronger mechanical and swelling properties,a faster degradation ratio,smaller pore size,and less favorable biological *** optimal 1%collagen hydrogel was used to print bi-layer skin in which fibroblasts and keratinocytes showed improved spreading and proliferation as compared to other developed *** Col/SA hydrogels presented suitable tunability and properties to be used as a bioink for bioprinting of skin aiming at finding applications as 3D models for wound healing research.

关键词： Bioink Bioprinting-Collagen sodium alginate hydrogel-Skin Wound healing Bionic

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Adaptable hydrogel with reversible linkages for regenerative medicine:Dynamic mechanical microenvironment for cells

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Bioactive Materials 2021年第5期6卷 1375-1387页

作者： Zongrui Tong Lulu Jin joaquim miguel oliveira Rui LReis Qi Zhong Zhengwei Mao Changyou Gao MOE Key Laboratory of Macromolecular Synthesis and Functionalization Department of Polymer Science and EngineeringZhejiang UniversityHangzhou310027China 3B’s Research Group I3Bs-Research Institute on BiomaterialsBiodegradables and BiomimeticsUniversity of MinhoHeadquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineAveParkZona Industrial da Gandra4805-017Barco GMRPortugal ICVS/3B’s-PT Government Associate Laboratory Braga/GuimarãesPortugal The Discoveries Centre for Regenerative and Precision Medicine Headquarters at University of MinhoAvepark4805-017BarcoGuimarãesPortugal Key Laboratory of Advanced Textile Materials&Manufacturing Technology Ministry of EducationNational Base for International Science and Technology Cooperation in Textiles and Consumer-Goods ChemistryZhejiang Sci-Tech University310018HangzhouChina

Hydrogels are three-dimensional platforms that serve as substitutes for native extracellular *** materials are starting to play important roles in regenerative medicine because of their similarities to native matrix in water content and *** would be very advantagoues for researchers to be able to regulate cell behavior and fate with specific hydrogels that have tunable mechanical properties as biophysical *** developments in dynamic chemistry have yielded designs of adaptable hydrogels that mimic dynamic nature of extracellular *** current review provides a comprehensive overview for adaptable hydrogel in regenerative medicine as ***,we outline strategies to design adaptable hydrogel network with reversible linkages according to previous findings in supramolecular chemistry and dynamic covalent ***,we describe the mechanism of dynamic mechanical microenvironment influence cell behaviors and fate,including how stress relaxation influences on cell behavior and how mechanosignals regulate matrix ***,we highlight techniques such as bioprinting which utilize adaptable hydrogel in regenerative *** conclude by discussing the limitations and challenges for adaptable hydrogel,and we present perspectives for future studies.

关键词： Adaptable hydrogel Dynamic mechanical microenvironment Supramolecular chemistry Dynamic covalent chemistry Yes-associated protein

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Preserving cognitive function in patients with Alzheimer's disease:The Alzheimer's disease neuroprotection research initiative(ADNRI)

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Neuroprotection 2023年第2期1卷 84-98页

作者： Jie Liu Heleen van Beusekom Xian-Le Bu Gong Chen Paulo Henrique Rosado de Castro Xiaochun Chen Xiaowei Chen Andrew N.Clarkson Tracy D.Farr Yuhong Fu Jianping Jia Jukka Jolkkonen Woojin Scott Kim Paula Korhonen Shen Li Yajie Liang Guang-Hui Liu Guiyou Liu Yu-Hui Liu Tarja Malm Xiaobo Mao joaquim miguel oliveira Mike M.Modo Pedro Ramos-Cabrer Karsten Ruscher Weihong Song Jun Wang Xuanyue Wang Yun Wang Haitao Wu Lize Xiong Yi Yang Keqiang Ye Jin-Tai Yu Xin-Fu Zhou Marietta Zille Colin L.Masters Piotr Walczak Boltze Johannes Xunming Ji Yan-Jiang Wang Department of Neurology Daping HospitalThird Military Medical UniversityChongqingChina Chongqing Key Laboratory of Ageing and Brain Diseases ChongqingChina Division of Experimental Cardiology Department of CardiologyErasmus MCUniversity Medical CenterRotterdamThe Netherlands Institute of Brain and Intelligence Third Military Medical UniversityChongqingChina Guangdong-HongKong-Macao Institute of CNS Regeneration(GHMICR) Jinan UniversityGuangzhouGuangdongChina Institute of Biomedical Sciences Federal University of Rio de JaneiroRio de JaneiroRio de JaneiroBrazil Fujian Key Laboratory of Molecular Neurology Department of Neurology and GeriatricsFujian Institute of GeriatricsFujian Medical University Union HospitalInstitute of NeuroscienceFujian Medical UniversityFuzhouFujianChina Guangyang Bay Laboratory Chongqing Institute for Brain and IntelligenceChongqingChina Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesShanghaiChina Department of Anatomy Brain Health Research Centre and Brain Research New ZealandUniversity of OtagoDunedinNew Zealand School of Life Sciences University of NottinghamNottinghamUK Brain and Mind Centre&School of Medical Sciences The University of SydneySydneyNew South WalesAustralia Innovation Center for Neurological Disorders and Department of Neurology Xuanwu HospitalNational Clinical Research Center for Geriatric DiseasesCapital Medical UniversityBeijingChina A.I.Virtanen Institute for Molecular Sciences University of Eastern FinlandKuopioFinland Department of Neurology and Psychiatry Beijing Shijitan HospitalCapital Medical UniversityBeijingChina Department of Diagnostic Radiology and Nuclear Medicine University of Maryland School of MedicineBaltimoreMarylandUSA University of Chinese Academy of Sciences BeijingChina State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Beijing Institute of Brain Disorders Laboratory of Brain DisordersMinistry of Sci

The global trend toward aging populations has resulted in an increase in the occurrence of Alzheimer's disease(AD)and associated socioeconomic *** metabolism of amyloid-β(Aβ)has been proposed as a significant pathomechanism in AD,supported by results of recent clinical trials using anti-Aβ***,the cognitive benefits of the current treatments are *** etiology of AD is multifactorial,encompassing Aβand tau accumulation,neuroinflammation,demyelination,vascular dysfunction,and comorbidities,which collectively lead to widespread neurodegeneration in the brain and cognitive ***,solely removing Aβfrom the brain may be insufficient to combat neurodegeneration and preserve *** attain effective treatment for AD,it is necessary to(1)conduct extensive research on various mechanisms that cause neurodegeneration,including advances in neuroimaging techniques for earlier detection and a more precise characterization of molecular events at scales ranging from cellular to the full system level;(2)identify neuroprotective intervention targets against different neurodegeneration mechanisms;and(3)discover novel and optimal combinations of neuroprotective intervention strategies to maintain cognitive function in AD *** Alzheimer's Disease Neuroprotection Research Initiative's objective is to facilitate coordinated,multidisciplinary efforts to develop systemic neuroprotective strategies to combat *** aim is to achieve mitigation of the full spectrum of pathological processes underlying AD,with the goal of halting or even reversing cognitive decline.

关键词： Alzheimer's disease early intervention neural regeneration neuroprotection systematic perspective

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Biomaterials and emerging technologies for tissue engineering and in vitro models

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Bio-Design and Manufacturing 2024年第3期7卷 237-239页

作者： J.miguel oliveira Rui L.Reis 3B’s Research Group I3Bs-Research Institute on BiomaterialsBiodegradables and BiomimeticsHeadquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineUniversity of MinhoAveParkZona Industrial da Gandra4805-017 BarcoGuimarãesPortugal ICVS/3B’s-PT Government Associate Laboratory 4806-909 Braga/GuimarãesPortugal

The latest advances in the field of biomaterials have opened new avenues for scientific breakthroughs in tissue engineer-ing which greatly contributed for the successful translation of tissue engineering products into the market/***-materials are easily processed to become similar to natural extracellular matrix,making them ideal temporary supports for mimicking the three-dimensional(3D)microenvironment required for maintaining the adequate cell/tissue functions both in vitro and in vivo^([1]).

关键词： breakthrough biomaterials engineer

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Rat cardiomyocyte H9c2(2-1)-based sulforhodamine B assay as a promising in vitro method to assess the biological component of effluent toxicity

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Journal of Environmental Sciences 2020年第10期32卷 163-170页

作者： Elsa T Rodrigues Susana F Nascimento Maria Joao Moreno Paulo J oliveira miguel A Pardal University of Coimbra Centre for Functional EcologyDepartment of Life SciencesCalcada Martim de FreitasCoimbra 3000-456Portugal University of Coimbra Coimbra Chemistry CenterDepartment of ChemistryCoimbra 3004-535Portugal Centre for Neuroscience and Cell Biology Uniuersity of CoimbraUC BiotechBiocant ParkCantanhede 3060-197Portugal

The treatment of wastewaters is crucial to maintain the ecological status of receiving waters,and thereby guarantee the protection of aquatic life and human *** quality evaluation is conventionally based on physicochemical parameters,but increasing attention has been paid to integrate physicochemical and biological ***,the regulatory use of fish in biological testing methods has been subject to various ethical and cost concerns,and in vitro cell-based assays have thus become an important topic of ***,the present study intends:(a) to evaluate the efficiency of two different sample pre-concentration techniques (lyophilisation and solid phase extraction) to assess the toxicity of municipal effluents on rat cardiomyoblast H9c2(2-1) cells,and (b) maximizing the use of the effluent sample collected,to estimate the environmental condition of the receiving *** gathered results demonstrate that the H9c2(2-1) sulforhodamine B-based assay is an appropriate in vitro method to assess biological effluent toxicity,and the best results were attained by lyophilising the sample as *** to its response,the H9c2(2-1) cell line might be a possible alternative in vitro model for fish lethal testing to assess the toxicity of municipal *** physicochemical status of the sample suggests a high potential for eutrophication,and iron exceeded the permissible level for wastewater discharge,possibly due to the addition of ferric chloride for wastewater *** general,the levels of carbamazepine and sulfamethoxazole are higher than those reported for other countries,and both surpassed the aquatic protective values for long-term exposure.

关键词： Municipal wastewater treatment plant effluent Lyophilisation Solid phase extraction Cell-based assays H9c2(2-1)cell line SRB assay

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Evaluation of the regional distribution of the pediatric surgery workforce and surgical load in Brazil

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World Journal of Pediatric Surgery 2023年第2期6卷 85-91页

作者： joaquim Bustorff-Silva Marcio Lopes Miranda Amanda Rosendo Ayla Gerk Antonio Goncalves oliveira-filho Pediatric Surgery State University of Campinas Medical SchoolCampinasBrazilPediatric SurgeryState University of Campinas Medical SchoolCampinasBrazil Medicine Pontificia Universidad Católica ArgentinaBuenos AiresArgentina

Objective The purpose of this study is to examine the regional distribution of the pediatric surgery workforce and the expected local demand for pediatric surgical procedures in *** We collected data on the pediatric surgical workforce,surgical volume,Gross Domestic Product per capita,and mortality for gastrointestinal tract malformations(MGITM)across the different regions of Brazil for *** Data from the Federal Medical Council reported 1515 pediatric surgery registries in Brazil,corresponding to 1414 pediatric surgeons(some pediatric surgeons are registered in more than one state),or 2.4 pediatric surgeons per 100000 children 14 years of age and *** were 828 men and 586 *** mean age was 51.5±12.8 years,and the mean time from graduation was 3.4±5.7 *** is a higher concentration of pediatric surgeons in the wealthier Central-West,South,and Southeast *** surgical volume ranged from 88 to 245 operations/year(average 146 operations/year)depending on the *** these,only nine(6.1%)were high-complexity(including neonatal)*** tended to be higher in the poorer North and Northeast regions than in other regions of *** Our findings suggest significant disparities in the surgical workforce and workload across Brazil related to socioeconomic *** with an increased surgical workforce were associated with lower *** average number of complex operations performed annually by each pediatric surgeon was considerably *** investment and well-defined health policies are imperative to enhance the quality of surgical care in the different regions of Brazil.

关键词： pediatric operations distribution

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Functionally graded additive manufacturing to achieve functionality specifications of osteochondral scaffolds

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Bio-Design and Manufacturing 2018年第1期1卷 69-75页

作者： Mario Monzon Chaozong Liu Sara Ajami miguel oliveira Ricardo Donate Viviana Ribeiro Rui L. Reis Departamento de Ingenieria Mecanica Universidad de Las Palmas de Gran Canaria Edificio de fabricacion integrada 35017 Las Palmas de GC Spain Division of Surgery and Interventional Science University College London Stanmore London HA7 4LP UK 3Bs Biomaterials Biodegradables and Biomimetics Universidade Do Minho Parque de Ciencia e Tecnologia Zona Industrial da Gandra 4805-17 Barco GMR Portugal Integrated and Advanced Manufacturing Processes Research Group Universidad de Las PaJmas de Gran Canaria Edificio de fabricacion integrada 35017 Las Palmas de GC Spain

Introduction Osteoarthritis （OA） is a degenerative joint disease, characterized by cartilage loss and changes in bone at the interface of a joint resulting in pain, stiffness and reduced mobility. OA is one of the most prevalent chronic conditions as identified in Bone and Joint Decade. According to the World Health Organization, 40% of people over the age of 70 have OA. This joint disease affects around 0.4 billion people with patients in Europe accounting for up to 30%. The figure is set to increase with the ageing problem.

关键词：骨性关节炎疾病治疗方法生物技术

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Indirect printing of hierarchical patient-specific scaffolds for meniscus tissue engineering

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Bio-Design and Manufacturing 2019年第4期2卷 225-241页

作者： Joao BCosta Joana Silva-Correia Sandra Pina Alain da Silva Morais Sílvia Vieira Hélder Pereira Joao Espregueira-Mendes Rui LReis joaquim M.oliveira B′s Research Group I3Bs-Research Institute on BiomaterialsBiodegradables and BiomimeticsUniversity of MinhoHeadquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineAveParkZona Industrial da Gandra4805-017 Barco GmrPortugal ICVS/3B’s-PT Government Associate Laboratory Braga/GuimaraesPortugal The Discoveries Centre for Regenerative and Precision Medicine Headquarters at University of MinhoAvepark4805-017 BarcoGuimar'sPortugal Ripoll y De Prado Sports Clinic:Murcia-Madrid FIFA Medical Centre of Excellence MurciaSpain Orthopedic Department Centro Hospitalar Póvoa de Varzim Vila do CondePortugal Clínica do Dragao Espregueira-Mendes Sports CentreFIFA Medical Centre of ExcellencePortoPortugal Dom Henrique Research Centre PortoPortugal Orthopedic Department University of MinhoBragaPortugal

The complex meniscus tissue plays a critical role in the knee. The high susceptibility to injury has led to an intense pursuit for better tissue engineering regenerative strategies, where scaffolds play a major role. In this study, indirect printed hierarchical multilayered sca ffolds composed by a silk fibroin (SF) upper layer and an 80/20 (w/w) ratio of SF/ionic-doped β-tricalcium phosphate (TCP) bottom layer were developed. Furthermore, a comparative analysis between two types of sca ffolds pro- duced using di fferent SF concentrations, i.e., 8% (w/v) (Hi8) and 16% (w/v) (Hi16) was performed. In terms of architecture and morphology, the produced sca ffolds presented homogeneous porosity in both layers and no di fferences were observed when comparing both sca ffolds. A decrease in terms of mechanical performance of the sca ffolds was observed when SF concentration decreased from 16 to 8% (w/v). Hi16 revealed a static compressive modulus of 0.66 ± 0.05 MPa and dynamical mechanical properties ranging from 2.17 ± 0.25 to 3.19 ± 0.38 MPa. By its turn, Hi8 presented a compressive modulus of 0.27 ± 0.08 MPa and dynamical mechanical properties ranging from 1.03 ± 0.08 MPa to 1.56 ± 0.13 MPa. In vitro bioactivity studies showed formation of apatite crystals onto the surface of Hi8 and Hi16 bottom layers. Human meniscus cells (hMCs) and human primary osteoblasts were cultured separately onto the top layer (SF8 and SF16) and bottom layer (SF8/TCP and SF16/TCP) of the hierarchical sca ffolds Hi8 and Hi16, respectively. Both cell types showed good adhesion and proliferation as denoted by the live/dead staining, Alamar Blue assay and DNA quanti fication analysis. Subcutaneous implantation in mice revealed weak in flammation and sca ffold’s integrity. The hierarchical indirect printed SF sca ffolds can be promising candidate for meniscus TE sca ffolding applications due their suitable mechanical properties, good biological performance and possibility of being applied in a patie

关键词： Patient-specific Indirect printing Hierarchical Silk fibroin Enzymatic-cross-linking Meniscus

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