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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

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Nanozyme‑Engineered Hydrogels for Anti‑Inflammation and Skin regeneration

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Nano-Micro Letters 2024年第6期16卷 127-179页

作者： Amal George Kurian Rajendra K.Singh Varsha Sagar Jung‑Hwan Lee Hae‑Won Kim Institute of Tissue regeneration Engineering(ITREN) Dankook UniversityCheonan 31116Republic of Korea Department of Nanobiomedical Science&BK21 NBM Global Research Center for Regenerative Medicine Dankook UniversityCheonan 31116Republic of Korea Department of Biomaterials Science School of DentistryDankook UniversityCheonan 31116Republic of Korea UCL Eastman‑Korea Dental Medicine Innovation centre Dankook UniversityCheonan 31116Republic of Korea Cell and Matter Institute Dankook UniversityCheonan 31116Republic of Korea Mechanobiology Dental Medicine Research Center Dankook UniversityCheonan 31116Republic of Korea

Inflammatory skin disorders can cause chronic scarring and functional impairments,posing a significant burden on patients and the healthcare system.Conventional therapies,such as corticosteroids and nonsteroidal anti-inflammatory drugs,are limited in efficacy and associated with adverse effects.Recently,nanozyme(NZ)-based hydrogels have shown great promise in addressing these challenges.NZ-based hydrogels possess unique therapeutic abilities by combining the therapeutic benefits of redox nanomaterials with enzymatic activity and the water-retaining capacity of hydrogels.The multifaceted therapeutic effects of these hydrogels include scavenging reactive oxygen species and other inflammatory mediators modulating immune responses toward a pro-regenerative environment and enhancing regenerative potential by triggering cell migration and differentiation.This review highlights the current state of the art in NZ-engineered hydrogels(NZ@hydrogels)for anti-inflammatory and skin regeneration applications.It also discusses the underlying chemo-mechano-biological mechanisms behind their effectiveness.Additionally,the challenges and future directions in this ground,particularly their clinical translation,are addressed.The insights provided in this review can aid in the design and engineering of novel NZ-based hydrogels,offering new possibilities for targeted and personalized skin-care therapies.

关键词： Nanozymes Hydrogels ROS scavenging Anti-inflammation Skin regeneration

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Unveiling protein corona composition:predicting with resampling embedding and machine learning

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Regenerative Biomaterials 2024年第1期3卷 27-33页

作者： Rong Liao Yan Zhuang Xiangfeng Li Ke Chen Xingming Wang Cong Feng Guangfu Yin Xiangdong Zhu Jiangli Lin Xingdong Zhang College of Biomedical Engineering National Engineering Research Centre for BiomaterialsSichuan UniversityChengdu610065China

Biomaterials with surface nanostructures effectively enhance protein secretion and stimulate tissue regeneration.When nanoparticles(NPs)enter the living system,they quickly interact with proteins in the body fluid,forming the protein corona(PC).The accurate prediction of the PC composition is critical for analyzing the osteoinductivity of biomaterials and guiding the reverse design of NPs.However,achieving accurate predictions remains a significant challenge.Although several machine learning(ML)models like Random Forest(RF)have been used for PC prediction,they often fail to consider the extreme values in the abundance region of PC absorption and struggle to improve accuracy due to the imbalanced data distribution.In this study,resampling embedding was introduced to resolve the issue of imbalanced distribution in PC data.Various ML models were evaluated,and RF model was finally used for prediction,and good correlation coefficient(R^(2))and root-mean-square deviation(RMSE)values were obtained.Our ablation experiments demonstrated that the proposed method achieved an R^(2) of 0.68,indicating an improvement of approximately 10%,and an RMSE of 0.90,representing a reduction of approximately 10%.Furthermore,through the verification of label-free quantification of four NPs:hydroxyapatite(HA),titanium dioxide(TiO_(2)),silicon dioxide(SiO_(2))and silver(Ag),and we achieved a prediction performance with an R^(2) value>0.70 using Random Oversampling.Additionally,the feature analysis revealed that the composition of the PC is most significantly influenced by the incubation plasma concentration,PDI and surface modification.

关键词： nanoparticles protein corona machine learming resampling technique feature analysis

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Nanotechnology for the management of COVID-19 during the pandemic and in the post-pandemic era

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National Science Review 2022年第10期9卷 230-242页

作者： Chun Xu Chang Lei Sepanta Hosseinpour Saso Ivanovski Laurence J.Walsh Ali Khademhosseini School of Dentistry The University of Queensland centre for orofacial regeneration Reconstruction and Rehabilitation (COR3) School of Dentistry The University of Queensland Australian Institute for Bioengineering and Nanotechnology The University of Queensland Terasaki Institute for Biomedical Innovation

Following the global COVID-19 pandemic,nanotechnology has been at the forefront of research efforts and enables the fast development of diagnostic tools,vaccines and antiviral treatment for this novel virus(SARS-CoV-2).In this review,we first summarize nanotechnology with regard to the detection of SARS-C oV-2,including nanoparticle-based techniques such as rapid antigen testing,and nanopore-based se quencing and sensing techniques.Then we investigate nanote chnology as it applies to the development of COVID-19 vaccines and anti-SARS-CoV-2 nanomaterials.We also highlight nanotechnology for the post-pandemic era,by providing tools for the battle with SARS-C oV-2 variants and for enhancing the global distribution of vaccines.Nanotechnology not only contributes to the management of the ongoing COVID-19 pandemic but also provides platforms for the prevention,rapid diagnosis,vaccines and antiviral drugs of possible future virus outbreaks.

关键词： COVID-19 SARS-CoV-2 diagnosis nanotechnology vaccines

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Advanced brain organoids for neuroinflammation disease modeling

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Neural regeneration Research 2024年第1期19卷 154-155页

作者： Sonia Sabate-Soler Henry Kurniawan Jens Christian Schwamborn Luxembourg centre for Systems Biomedicine University of LuxembourgEsch-sur-AlzetteLuxembourg

Brain organoids mimic closely the embryonic human brain:Over the last decade,the development of human organoid systems has evolved rapidly.Different tissues have been modeled with organoids,such as the gut,lung,liver,kidney retina and brain.These systems have a high cellular heterogeneity,with many cell types integrated into the same system.Organoids'cellular populations interact between and amongst each other in a cellular and molecular level,which represents an advantage with respects to monolayer 2D cell culture systems.

关键词： inflammation lung kidney

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Effects of Lycium barbarum polysaccharide on cytokines in adolescents with subthreshold depression:a randomized controlled study

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Neural regeneration Research 2024年第9期19卷 2036-2040页

作者： Xiaoyue Li Tao Liu Xuan Mo Runhua Wang Xueyan Kong Robin Shao Roger S.Mclntyre Kwok-Fai So Kangguang Lin Department of Affective Disorders The Affiliated Brain Hospital of Guangzhou Medical University(Guangzhou Huiai Hospital)GuangzhouGuangdong ProvinceChina Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Department of Psychiatry The Fifth Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Mood Disorders Psychopharmacology Unit Poul Hansen Family Centre for DepressionUniversity Health NetworkTorontoONCanada Department of Psychiatry University of TorontoTorontoONCanada Brain and Cognition Discovery Foundation TorontoCanada Ministry of Education Joint International Research Laboratory of CNS regeneration Jinan UniversityGuangzhouGuangdong ProvinceChina Neuroscience and Neurorehabilitation Institute University of Health and Rehabilitation SciencesQingdaoShandong ProvinceChina

Strong evidence has accumulated to show a correlation between depression symptoms and inflammatory responses.Moreover,anti-inflammatory treatment has shown partial effectiveness in alleviating depression symptoms.Lycium barbarum polysaccharide(LBP),derived from Goji berries,exhibits notable antioxidative and anti-inflammatory properties.In our recent double-blinded randomized placebo-controlled trial,we found that LBP significantly reduced depressive symptoms in adolescents with subthreshold depression.It is presumed that the antidepressant effect of LBP may be associated with its influence on inflammatory cytokines.In the double-blinded randomized controlled trial,we enrolled 29 adolescents with subthreshold depression and randomly divided them into an LBP group and a placebo group.In the LBP group,adolescents were given 300 mg/d LBP.A 6-week follow up was completed by 24 adolescents,comprising 14 adolescents from the LBP group(15.36±2.06 years,3 men and 11 women)and 10 adolescents from the placebo group(14.9±1.6 years,2 men and 8 women).Our results showed that after 6 weeks of treatment,the interleukin-17A level in the LBP group was lower than that in the placebo group.Network analysis showed that LBP reduced the correlations and connectivity between inflammatory factors,which were associated with the improvement in depressive symptoms.These findings suggest that 6-week administration of LBP suppresses the immune response by reducing interleukin-17A level,thereby exerting an antidepressant effect.

关键词： adolescents cytokines efficacy Goji berry inflammatory responses interleukin-17A Lycium barbarum polysaccharide randomized controlled study subthreshold depression

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Constructing a biofunctionalized 3D-printed gelatin/sodium alginate/chitosan tri-polymer complex scaffold with improvised biological andmechanical properties for bone-tissue engineering

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Bio-Design and Manufacturing 2024年第1期7卷 57-73页

作者： Amit Kumar Singh Krishna Pramanik Amit Biswas centre of Excellence in Tissue Engineering Department of Biotechnology and Medical EngineeringNational Institute of TechnologyRourkela 769008India

Sodium alginate(SA)/chitosan(CH)polyelectrolyte scaffold is a suitable substrate for tissue-engineering application.The present study deals with further improvement in the tensile strength and biological properties of this type of scaffold to make it a potential template for bone-tissue regeneration.We experimented with adding 0%–15%(volume fraction)gelatin(GE),a protein-based biopolymer known to promote cell adhesion,proliferation,and differentiation.The resulting tri-polymer complex was used as bioink to fabricate SA/CH/GEmatrices by three-dimensional(3D)printing.Morphological studies using scanning electron microscopy revealed the microfibrous porous architecture of all the structures,which had a pore size range of 383–419μm.X-ray diffraction and Fourier-transform infrared spectroscopy analyses revealed the amorphous nature of the scaffold and the strong electrostatic interactions among the functional groups of the polymers,thereby forming polyelectrolyte complexes which were found to improve mechanical properties and structural stability.The scaffolds exhibited a desirable degradation rate,controlled swelling,and hydrophilic characteristics which are favorable for bone-tissue engineering.The tensile strength improved from(386±15)to(693±15)kPa due to the increased stiffness of SA/CH scaffolds upon addition of gelatin.The enhanced protein adsorption and in vitro bioactivity(forming an apatite layer)confirmed the ability of the SA/CH/GE scaffold to offer higher cellular adhesion and a bone-like environment to cells during the process of tissue regeneration.In vitro biological evaluation including the MTT assay,confocal microscopy analysis,and alizarin red S assay showed a significant increase in cell attachment,cell viability,and cell proliferation,which further improved biomineralization over the scaffold surface.In addition,SA/CH containing 15%gelatin designated as SA/CH/GE15 showed superior performance to the other fabricated 3D structures,demonstrating its potential for use in bone-tissue engineering.

关键词： Scaffold Biomaterial Sodium alginate Chitosan Gelatin 3D printing Tissue engineering

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Transcranial photobiomodulation for the brain: a wide range of clinical applications

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Neural regeneration Research 2024年第3期19卷 483-484页

作者： Michael R.Hamblin Laser Research centre Faculty of Health ScienceUniversity of Johannesburg-Doornfontein CampusDoornfonteinSouth Africa

Photobiomodulation therapy(PBMT)is a rapidly growing approach to the healing,stimulation,protection,and regeneration of many human organs and tissue types.PBMT started in the 1960s as low-level laser therapy for wound healing,but since then the introduction of light-emitting diodes(LEDs)has dramatically increased the number of applications and reports of positive results.PBMT generally uses red(620-700 nm)and/or near-infrared(780-1270 nm)wavelengths of light at an intensity that causes no tissue heating,and its activity is based on well-established biological and cellular mechanisms(de Freitas and Hamblin,2016).While laser therapists continue to use various types of laser in their office practice,LEDs are ideally suited for home use devices because they are completely safe and without any known significant adverse effects.Among the various body parts on which PBMT has been shown to exert beneficial effects,the brain stands out as perhaps the most promising overall.PBMT has been shown to reduce neuroinflammation,while increasing mitochondrial function,oxygen consumption,and blood flow within the brain(Hamblin,2016).Moreover,PBMT can stimulate the processes of synaptogenesis,neurogenesis,and neuroplasticity thus helping the brain to heal itself.

关键词： healing stimulation wound

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The immune system: uncharted pathways between senses and the brain

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Neural regeneration Research 2024年第6期19卷 1173-1174页

作者： Noelia Casares Mar Cuadrado-Tejedor Ana García-Osta Juan José Lasarte Immunology and Immunotherapy Program Centre for Applied Medical Research (CIMA) University of NavarraIDISNA Division of Gene Therapy for Neurological Disorders Centre for Applied Medical Research (CIMA) University of NavarraIDISNA Pathology Anatomy and Physiology Department School of Medicine University of NavarraIDISNA

Humans and animals use the classic five senses-sight, hearing, touch, smell, and taste-to detect and monitor their environment, with the sense of position and movement often referred to as the sixth sense. The perception of external signals through the senses is essential to an organism’s survival, transmitting signals to the central nervous system(CNS) and prompting physiological changes in other biological systems. In addition to the direct effects of sense-induced mediators in the brain,

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Does astrocytic L-lactate enhance cognition through myelination?

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Neural regeneration Research 2024年第6期19卷 1167-1168页

作者： Mastura Akter Ying Li Department of Neuroscience City University of Hong Kong Department of Biomedical Sciences City Universit of Hong Kong centre for Regenerative Medicine and Health Hong Kong Institute of Science & Innovation Chinese Academy of Sciences centre for Biosystems Neuroscience and Nanotechnology City University of Hong Kong

Introduction: Astrocytes, the predominant glial cell in the brain, play a vital role in a plethora of central ner vous system functions. They are the major storage site of glycogen in the central nervous system. They produce L-lactate by glycogenolysis and glycolysis which is then transported to neurons(Magistreti and Allaman,

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