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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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A self-fused hydrogel for the treatment of glottic insufficiency through outstanding durability,Extracellular matrix-inducing bioactivity and function preservation

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Bioactive Materials 2023年第6期24卷 54-68页

作者： Chen-Yu Zou Juan-Juan Hu Dan Lu Qian-Jin Li Yan-Lin Jiang Rui Wang Hai-Yang Wang Xiong-Xin Lei Jesse Li-Ling Hui Yang Hui-Qi Xie Laboratory of Stem Cell and Tissue Engineering Orthopedic Research InstituteMed-X Center for MaterialsState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduSichuan610041PR China Department of Otolaryngology Head and Neck SurgeryWest China HospitalSichuan UniversityChengduSichuan610041PR China Department of Medical Genetics West China Second HospitalSichuan UniversityChengduSichuan610041PR China

Injection laryngoplasty with biomaterials is an effective technique to treat glottic insufficiency.However,the inadequate durability,deficient pro-secretion of Extracellular matrix(ECM)and poor functional preservation of current biomaterials have yielded an unsatisfactory therapeutic effect.Herein,a self-fusing bioactive hydrogel comprising modified carboxymethyl chitosan and sodium alginate is developed through a dual-crosslinking mechanism(photo-triggered and dynamic covalent bonds).Owing to its characteristic networks,the synergistic effect of the hydrogel for vocal folds(VFs)vibration and phonation is adequately demonstrated.Notably,owing to its inherent bioactivity of polysaccharides,the hydrogel could significantly enhance the secretion of major components(type I/III collagen and elastin)in the lamina propria of the VFs both in vivo and in vitro.In a rabbit model for glottic insufficiency,the optimized hydrogel(C1A1)has demonstrated a durability far superior to that of the commercially made hyaluronic acid(HA)Gel.More importantly,owing to the ECM-inducing bioactivity,the physiological functions of the VFs treated with the C1A1 hydrogel also outperformed that of the HA Gel,and were similar to those of the normal VFs.Taken together,through a simple-yet-effective strategy,the novel hydrogel has demonstrated outstanding durability,ECM-inducing bioactivity and physiological function preservation,therefore has an appealing clinical value for treating glottic insufficiency.

关键词： Glottic insufficiency Self-fusion Hydrogel Extracellular matrix Physiological function

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3D-printed dermis-specific Extracellular matrix mitigates scar contraction via inducing early angiogenesis and macrophage M2 polarization

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Bioactive Materials 2022年第4期7卷 236-246页

作者： Lei Chen Zhiyong Li Yongtai Zheng Fei Zhou Jingling Zhao Qiyi Zhai Zhaoqiang Zhang Tianrun Liu Yongming Chen Shaohai Qi Department of Burns Laboratory of General SurgeryThe First Affiliated HospitalSunYat-Sen UniversityGuangzhou510080China School of Materials Science and Engineering Centre of Functional BiomaterialsKey Laboratory of Polymeric Composite Materials and Functional Materials of Ministry of EducationGD Research Centre for Functional Biomaterials Engineering and TechnologySun Yat-sen UniversityGuangzhou510275China Department of Oral and Maxillofacial Surgery Stomatological HospitalSouthern Medical UniversityNo.366South of Jiangnan BoulevardGuangzhou510280China Department of Otorhinolaryngology Head and Neck Surgery The Sixth Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina

Scar contraction frequently happens in patients with deep burn injuries.Hitherto,porcine dermal Extracellular matrix(dECM)has supplied microenvironments that assist in wound healing but fail to inhibit scar contraction.To overcome this drawback,we integrate dECM into three-dimensional(3D)-printed dermal analogues(PDA)to prevent scar contraction.We have developed thermally gelled,non-rheologically modified dECM powder(dECMp)inks and successfully transformed them into PDA that was endowed with a micron-scale spatial structure.The optimal crosslinked PDA exhibited desired structure,good mechanical properties as well as excellent biocompatibility.Moreover,in vivo experiments demonstrated that PDA could significantly reduced scar contraction and improved cosmetic upshots of split thickness skin grafts(STSG)than the commercially available dermal templates and STSG along.The PDA has also induced an early,intense neovascularization,and evoked a type-2-like immune response.PDA’s superior beneficial effects may attribute to their desired porous structure,the well-balanced physicochemical properties,and the preserved dermis-specific ECM cues,which collectively modulated the expression of genes such as Wnt11,ATF3,and IL1β,and influenced the crucial endogenous signalling pathways.The findings of this study suggest that PDA is a clinical translatable material that possess high potential in reducing scar contraction.

关键词： Extracellular matrix Dermal analogues Scar contraction Macrophage Angiogenesis

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A cell retrievable strategy for harvesting Extracellular matrix as active biointerface

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Journal of Materials Science & Technology 2022年第35期130卷 44-52页

作者： Xiangyu Dong Shuxiang Zhang Yi Xu Longquan Chen Qiang Wei Changsheng Zhao College of Polymer Science and Engineering State Key Laboratory of Polymer Materials and EngineeringSichuan UniversityChengdu 610065China School of Physics University of Electronic Science and Technology of ChinaChengdu 610054China College of Biomedical Engineering Sichuan UniversityChengdu 610065China State Key Laboratory of Molecular Engineering of Polymers Fudan UniversityShanghai 200433China

Extracellular matrix(ECM) provides a variety of physical and chemical cues for cells. Here, a very simple and smart method is developed to glue living cells away for harvesting their ECMs. The obtained ECM coatings show less cell fragment residues comparing with those obtained by the traditional cell lysis. The glued cell sheets can even be re-cultured and reused after transferring to new environment. This moderate way well maintains the activity of the ECM proteins, which can promote cell adhesion and growth.Strikingly, the ECM coatings acquired from different functional cells can guide stem cell differentiation,which is attributed to the natural physical and biochemical cues on ECM coatings. Consequently, this method provides a substantial progress for preparing natural ECM coatings and shows promising potential in regenerative medicine and other related fields of biomedical engineering.

关键词： Extracellular matrix Regenerative medicine Biocoatings Cell sheets Differentiation

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Decellularized Extracellular matrix:A promising strategy for skin repair and regeneration

Engineered Regeneration

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Engineered Regeneration 2023年第4期4卷 357-374页

作者： Shengjie Jiang Yu Zhuang Ming Cai Xudong Wang Kaili Lin Department of Oral and Cranio-maxillofacial Surgery Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of Medicine/College of StomatologyShanghai Jiao Tong University/National Center for Stomatology/National Clinical Research Center for Oral Diseases/Shanghai Key Laboratory of Stomatology/Shanghai Research Institute of StomatologyShanghai 200011China

The skin is an important organ of the human body that resists external threats but lacks sufficient self-regeneration ability when severe damage occurs.However,most of the available skin substitutes cannot achieve ideal restoration of complex structures and multiple functions of native skin tissues.Fortunately,the advent of decellularized Extracellular matrix(dECM)offers a promising approach to overcome these obstacles.The dECM,derived from the natural Extracellular matrix(ECM),possesses a similar structure and composition,which constructs an environment favorable for cell performance in regeneration.Moreover,dECM retains good bioactivity,low immunogenicity,and high availability,making it a suitable biomaterial for skin repair and regeneration.In this review,various decellularization methods and subsequent evaluations of dECM are introduced first,and the main sources of dECM are then presented.Furthermore,the recent progress of dECM-based biomaterials applied in skin regeneration and future perspectives are summarized.

关键词： Decellularization Extracellular matrix Skin regeneration Biomaterial Bioink

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Extracellular matrix and nitric oxide based functional coatings for vascular stents

Engineered Regeneration

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Engineered Regeneration 2022年第2期3卷 149-153页

作者： Quhan Cheng Muhammad Shafiq Muhammad Rafique Li Shen Xiumei Mo Kai Wang Key Laboratory of Bioactive Materials Ministry of EducationCollege of Life SciencesNankai UniversityTianjin 300071China State Key Laboratory for Modification of Chemical Fibers and Polymer Materials Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative MedicineCollege of ChemistryChemical Engineering and BiotechnologyDonghua UniversityShanghai 201620China Department of Cardiology Shanghai Institute of Cardiovascular DiseasesZhongshan HospitalFudan UniversityShanghai 200032China National Clinical Research Center for Interventional Medicine Shanghai 200032China.

Cardiovascular diseases cause huge morbidity and mortality worldwide.Recently,vascular stents have been most frequently used to treat cardiovascular diseases thanks to their effectiveness at dilating blood vessels and main-taining the circulation of blood.However,stent expansion leads to endothelium injury posing thrombogenic and in-stent restenosis(ISR).In addition,the bioinertness and an acute lack of endothelium-like function on the surface of implanted vascular stents compromise their performance.Functional coatings of vascular stents to mimic endothelium-and Extracellular matrix(ECM)-like functions could prevent thrombosis,inhibit the over-growth of smooth muscle cells(SMCs),and promote the rapid restoration of native endothelium,hence effec-tively suppressing stent-related complications.Noticeably,ECM-based coatings including a multitude of bioactive molecular,such as growth factors,heparin,hyaluronic acid(HA)and so on,have been proven to play important effects on regulating ECs/SMCs behavior and improving blood compatibility of stents.Additionally,nitric oxide(NO),which is fundamental to the endothelium-mediated anti-thrombogenesity,anti-intimal hyperplasia and anti-inflammation,has been leveraged to improve vascular stent functions.Therefore,this review will highlight different strategies and biological role of ECM and NO based functional coatings on vascular stent.Lastly,some potential important factors for stents development are suggested as well.

关键词： Vascular stent Nitric oxide Extracellular matrix Functional coating

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Growth factor delivery using Extracellular matrix-mimicking substrates for musculoskeletal tissue engineering and repair

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Bioactive Materials 2021年第7期6卷 1945-1956页

作者： Robert C.H.Gresham Chelsea S.Bahney J.Kent Leach UC Davis Department of Biomedical EngineeringDavisCAUSA Steadman Phillippon Research Institute VailCOUSA UCSF Orthopaedic Trauma Institute San FranciscoCAUSA UC Davis Health Department of Orthopaedic SurgeryDavisCAUSA

Therapeutic approaches for musculoskeletal tissue regeneration commonly employ growth factors(GFs)to influence neighboring cells and promote migration,proliferation,or differentiation.Despite promising results in preclinical models,the use of inductive biomacromolecules has achieved limited success in translation to the clinic.The field has yet to sufficiently overcome substantial hurdles such as poor spatiotemporal control and supraphysiological dosages,which commonly result in detrimental side effects.Physiological presentation and retention of biomacromolecules is regulated by the Extracellular matrix(ECM),which acts as a reservoir for GFs via electrostatic interactions.Advances in the manipulation of extracellular proteins,decellularized tissues,and synthetic ECM-mimetic applications across a range of biomaterials have increased the ability to direct the presentation of GFs.Successful application of biomaterial technologies utilizing ECM mimetics increases tissue regeneration without the reliance on supraphysiological doses of inductive biomacromolecules.This review describes recent strategies to manage GF presentation using ECM-mimetic substrates for the regeneration of bone,cartilage,and muscle.

关键词： Growth factor Extracellular matrix Spatiotemporal control Tissue engineering Affinity

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Karacoline,identified by network pharmacology, reduces degradation of the Extracellular matrix in intervertebral disc degeneration via the NF-κB signaling pathway

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Journal of Pharmaceutical Analysis 2020年第1期10卷 13-22页

作者： Xiaoli Zhou Yingying Hong Yulin Zhan Department of Traditional Chinese Medicine College of MedicineShanghai University of Traditional Chinese MedicineShanghai201203China Department of Biology School of Fisheries and Life SciencesShanghai Ocean UniversityShanghai201306China Orthopedics Department Shanghai Sixth People’s Hospital East Affiliated to Shanghai University of Medicine&Health ScienceShanghai201306China

Karacoline is a compound found in the plant Aconitum kusnezoffii Reichb.Although Aconitum kusnezoffii Reichb is widely used for the treatment of pain,very few studies have been carried out on the use of karacoline due to its potential toxicity.In this study,we selected key matrix metalloproteinases(MMPs),collagen II,and aggrecan as targets due to their association with intervertebral disc degeneration(IDD).Using these targets,we then used network pharmacology to predict a series of molecules that might exert therapeutic effects on IDD.Of these molecules,karacoline was predicted to have the best effect.Tumor necrosis factor(TNF)-a is known to promote the degeneration of the Extracellular matrix in IDD.We therefore applied different concentrations of karacoline(0,1.25,or 12.88 mM)along with 100 ng/mL TNF-a to rat nucleus pulposus cells and found that karacoline reduced the expression of MMP-14 in IDD by inhibiting the nuclear factor(NF)-κB pathway,while collagen II and aggrecan expression was increased.This suggested that Extracellular matrix degradation was inhibited by karacoline(P<0.05).Our data therefore reveal a new clinical application of karacoline and provide support for the use of network pharmacology in predicting novel drugs.

关键词： Karacoline Network pharmacology Intervertebral disc degeneration Extracellular matrix matrix metalloproteinases

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Prospective of Extracellular matrix and drug correlations in disease management

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Asian Journal of Pharmaceutical Sciences 2021年第2期16卷 147-160页

作者： Varish Ahmad Health Information Technology Department Faculty of Applied StudiesKing Abdulaziz UniversityJeddah 21589Kingdom of Saudi Arabia

The Extracellular matrix(ECM)comprises of many structural molecules that constitute the extracellular environment.ECM molecules are characterized by specific features like diversity,complexity and signaling,which are also results of improvement or development of disease mediated by some physiological changes.Several drugs have also been used to manage diseases and they have been reported to modulate ECM assembly,including physiological changes,beyond their primary targets and ECM metabolism.This review highlights the alteration of ECM environment for diseases and effect of different classes of drugs like nonsteroidal anti-inflammatory drugs,immune suppressant drug,steroids on ECM or its components.Thus,it is summarized from previously conducted researches that diseases can be managed by targeting specific components of ECM which are involved in the pathophysiology of diseases.Moreover,the drug delivery focused on targeting the ECM components also has the potential for the discovery of targeted and site specific release of drugs.Therefore,ECM or its components could be future targets for the development of new drugs for controlling various disease conditions including neurodegenerative diseases and cancers.

关键词： Extracellular matrix Disease Pharmacotherapeutics Drug target

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Changes in Extracellular matrix in different stages of colorectal cancer and their effects on proliferation of cancer cells

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World Journal of Gastrointestinal Oncology 2020年第3期12卷 267-275页

作者： Zhu-Lin Li Zhen-Jun Wang Guang-Hui Wei Yong Yang Xiao-Wan Wang Department of General Surgery Beijing Chaoyang HospitalCapital Medical UniversityBeijing 100020China Institute of Basic Medical Sciences Chinese Academy of Medical SciencesBeijing 100005China

BACKGROUND The Extracellular matrix is the main component of the tumor microenvironment.Extracellular matrix remodels with the oncogenesis and development of tumors.Previous studies usually focused on the changes of proteins in normal colorectal tissues and colorectal cancers.Little is known about the changes in the Extracellular matrix in different stages of colorectal cancer and the effects of these changes on the development of this cancer.AIM To test the changes of type I collagen,type IV collagen,matrix metalloproteinase-2(MMP-2),matrix metalloproteinase-9(MMP-9),and tissue inhibitor of metalloproteinase-3(TIMP-3)in different stages of colorectal cancer and the effects of these changes on the proliferation of cancer cells.METHODS The Extracellular matrix from various stages of colorectal cancer and normal colon tissue was obtained by using acellular technology.We used proteomics to detect the differential expression of proteins between normal colon tissues and colorectal cancer tissues,and then we used Western blot to observe their expression in each stage of colorectal cancer and in normal colon tissue.By coculturing the Extracellular matrix and HT29 colon cancer cells in vivo and in vitro,we tested the cancer cell proliferation rate in vitro by methyl thiazolyl tetrazolium(MTT)assay and in vivo by measuring the tumor volume.RESULTS The expression of type I collagen and MMP-2 increased with increased tumor stage.The expression of MMP-9 was higher in colorectal cancer tissues and was highest in stage III cancer.The expression of type IV collagen and TIMP-3 decreased with increased tumor stage.The proliferation rate of cancer cells in the Extracellular matrix of colorectal cancer was higher than that in the Extracellular matrix of the normal colon.CONCLUSION These data suggest that the Extracellular matrix structure and composition become disorganized during the development of tumors,which is more conducive for the growth of cancer cells.

关键词： Colorectal cancer Extracellular matrix MMP Proliferation Collagen TIMP

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