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机械性能增强的聚乙烯醇/丙烯酰胺水凝胶通过旁分泌作用调节免疫和血管化过程促进皮肤缺损的修复（英文）

Engineering 2024年第6期 138-151页

作者：王鹏钱丽萍梁绘昕黄剑浩金晶谢春梅薛斌赖建诚张祎博蒋利锋李澜蒋青 State Key Laboratory of Pharmaceutical Biotechnology Division of Sports Medicine and Adult Reconstructive Surgery Department of Orthopedic Surgery Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School Nanjing University Jiangsu Engineering research center for 3d Bioprinting Institute of Medical 3d Printing Nanjing University Centre for Experimental Animals Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School Nanjing University College of Aeroplane Engineering Nanjing University of Aeronautics and Astronautics National Laboratory of Solid State Microstructures Department of Physics Nanjing University department of Chemical Engineering Stanford University department of Orthopedic Surgery The Second Affiliated Hospital Zhejiang University School of Medicine Orthopedic Research Institute of Zhejiang UniversityKey Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province

Hydrogel-based tissue-engineered skin has attracted increased attention due to its potential to restore the structural integrity and functionality of skin. However, the mechanical properties of hydrogel scaffolds and natural skin are substantially different. Here, we developed a polyvinyl alcohol(PVA)/acrylamide based interpenetrating network(IPN) hydrogel that was surface modified with polydopamine(PdA) and termed dopa-gel. The dopa-gel exhibited mechanical properties similar to native skin tissue and a superior ability to modulate paracrine functions. Furthermore, a tough scaffold with tensile resistance was fabricated using this hydrogel by three-dimensional printing. The results showed that the interpenetration of PVA, alginate, and polyacrylamide networks notably enhanced the mechanical properties of the hydrogel. Surface modification with PdA endowed the hydrogels with increased secretion of immunomodulatory and proangiogenic factors. In an in vivo model, dopa-gel treatment accelerated wound closure, increased vascularization, and promoted a shift in macrophages from a proinflammatory M1 phenotype to a prohealing and anti-inflammatory M2 phenotype within the wound ***, the focal adhesion kinase(FAK)/extracellular signal-related kinase(ErK) signaling pathway may mediate the promotion of skin defect healing by increasing paracrine secretion via the ***, proangiogenic factors can be induced through rho-associated kinase-2(rOCK-2)/vascular endothelial growth factor(VEGF)-mediated paracrine secretion under tensile stress conditions. Taken together, these findings suggest that the multifunctional dopa-gel, which has good mechanical properties similar to those of native skin tissue and enhanced immunomodulatory and angiogenic properties, is a promising scaffold for skin tissue regeneration.

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Modeling the gene delivery process of the needle array-based tissue nanotransfection

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Nano research 2022年第4期15卷 3409-3421页

作者： Zhigang Li Yi Xuan Subhadip Ghatak Poornachander rGuda Sashwati roy Chandan K.Sen Indiana center for regenerative medicine and Engineering Indiana University Health Comprehensive Wound CenterDepartment of SurgeryIndiana University School of MedicineIndianapolisIN 46202USA Birck Nanotechnology center and Weldon School of Biomedical Engineering Purdue UniversityWest LafayetteIN 47907USA

Hollow needle array-based tissue nanotransfection(TNT)presents an in vivo transfection approach that directly translocate exogeneous genes to target tissues by using electric *** this work,the gene delivery process of TNT was simulated and experimentally *** adopted the asymptotic method and cell-array-based model to investigate the electroporation behaviors of cells within the skin *** distribution of nonuniform electric field across the skin results in various electroporation behavior for each *** underneath the hollow microchannels of the needle exhibited the highest total pore numbers compared to others due to the stronger localized electric *** percentage of electroporated cells within the skin structure,with pore radius over 10 nm,increases from 25%to 82%as the applied voltage increases from 100 to 150 V/***,the gene delivery behavior across the skin tissue was investigated through the multilayer-stack-based *** delivery distance increased nonlinearly as the applied voltage and pulse number increased,which mainly depends on the diffusion characteristics and electric conductivity of each *** was also found that the skin is required to be exfoliated prior to the TNT procedure to enhance the delivery *** work provides the foundation for transition from the study of murine skin to translation use in large animals and human settings.

关键词： tissue nanotransfection silicon needle array hollow needle array electroporation electrophoresis gene delivery

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Single cell analysis reveals inhibition of angiogenesis attenuates the progression of heterotopic ossification in Mkx^(−/−)mice

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Bone research 2022年第4期10卷 715-725页

作者： Junxin Lin Yuwei Yang Wenyan Zhou Chao dai Xiao Chen Yuanhao Xie Shan Han Huanhuan Liu Yejun Hu Chenqi Tang Varitsara Bunpetch dandan Zhang Yishan Chen Xiaohui Zou di Chen Wanlu Liu Hongwei Ouyang dr.Li dak Sum&Yip Yio Chin center for Stem Cells and regenerative medicine and Department of Orthopedic Surgery of the Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina department of Sports medicine Zhejiang University School of MedicineHangzhouChina Zhejiang University-University of Edinburgh Institute Zhejiang University School of Medicineand Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang ProvinceHangzhouChina China Orthopedic regenerative medicine Group(COrMed) HangzhouChina department of Pathology Zhejiang University School of MedicineHangzhouChina Clinical research center The First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouChina center for reproductive medicine The Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouChina

Tendon heterotopic ossification(HO)is characterized by bone formation inside tendon tissue,which severely debilitates people in their daily *** therapies fail to promote functional tissue repair largely due to our limited understanding of HO ***,we investigate the pathological mechanism and propose a potential treatment method for *** assays showed that the Mohawk(MKX)expression level was decreased in human tendon HO tissue,coinciding with spontaneous HO and the upregulated expression of osteochondrogenic and angiogenic genes in the tendons of Mkx^(−/−)***-cell rNA sequencing analyses of wild-type and Mkx^(−/−)tendons identified three cell types and revealed the excessive activation of osteochondrogenic genes during the tenogenesis of Mkx^(−/−)tendon ***-cell analysis revealed that the gene expression program of angiogenesis,which is strongly associated with bone formation,was activated in all cell types during ***,inhibition of angiogenesis by the small-molecule inhibitor BIBF1120 attenuated bone formation and angiogenesis in the Achilles tendons of both Mkx mutant mice and a rat traumatic model of *** findings provide new insights into the cellular mechanisms of tendon HO and highlight the inhibition of angiogenesis with BIBF1120 as a potential treatment strategy for HO.

关键词： angiogenesis ossification analysis

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Polyaspers A and B,the First Ergosterol-Polyether Adducts with Unprecedented 6/6/6/5/5/6/6/6/6 Nonacyclic Architecture from Aspergillus ***507

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Chinese Journal of Chemistry 2024年第7期42卷 743-751页

作者： Hong Hu Lanqin Li Zhengyi Shi Xueqi Lan Yeting Zhang Xinye Huang Xincai Hao Qun Zhou Weiguang Sun Changxing Qi Yonghui Zhang Hubei Key Laboratory of Natural Medicinal Chemistry and resource Evaluation Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China Institute of Organ Transplantation Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology Key Laboratory of Organ TransplantationMinistry of EducationNHC Key Laboratory of Organ TransplantationKey Laboratory of Organ TransplantationChinese Academy of Medical SciencesWuhanHubei 430030China Hubei Key Laboratory of Wudang Local Chinese medicine research Hubei Engineering Technology Center for Comprehensive Utilization of Medicinal PlantsCollege of PharmacyHubei University of MedicineShiyanHubei 442000China

Psoriasis is a chronic immune-mediated inflammatory skin disease and the TNF-αis an important therapeutic target of this *** our continuous study of bioactive natural products from fungi,the first ergosterol-polyether adducts,polyaspers A(1)and B(2),along with two known ergosterols,(36,5α,6α,22E)-5,6-epoxy-3-hydroxyergosta-8,22-dien-7-one(3)and calvasterol B(4),were iso-lated from Aspergillus *** elucidation was accomplished by extensive spectroscopic analysis and single-crystal X-ray diffraction *** A and B possessing an unequalled 6/6/6/5/5/6/6/6/6 nonacyclic system,and their biosynthetic path-ways were proposed to include intermolecular cyclization and diels-Alder *** screen of these isolates showed that 1-3 could improve the cell viability in an actinomycin d/TNF-αinduced L929 cells death model,with the EC50 values of 49.85,46.75 and 4.99μmol/L,respectively,and the activity of 3 was even comparable with that of the positive control *** bioactive investigations discovered 3 could suppress the inflammatory response simulated with TNF-αin HaCaT *** an imiquimod-induced psoriasis murine model,3 significantly restrained the development of psoriasis symptoms and reduced the expression of IL-17 and IL-23,presenting an anti-psoriatic *** such,those ergosterol derivatives,might serve as lead compounds for the development of novel TNF-αinhibitory agents in the clinical treatment of psoriasis.

关键词： Psoriasis Aspergillus sp.TJ507 TNF-α Ergosterol-polyether adducts Inflammatory skin disease

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Connecting past and present:single-cell lineage tracing

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Protein & Cell 2022年第11期13卷 790-807页

作者： Cheng Chen Yuanxin Liao Guangdun Peng center for Cell Lineage and development CAS Key Laboratory of Regenerative BiologyGuangdong Provincial Key Laboratory of Stem Cell and Regenerative MedicineGIBH-HKU Guangdong-Hong Kong Stem Cell and Regenerative Medicine Research CentreGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou 510530China center for Cell Lineage and Atlas Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory)Guangzhou 510005China Institute for Stem Cell and regeneration Chinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China

Central to the core principle of cell theory,depicting cells'history,state and fate is a fundamental goal in modern *** leveraging clonal analysis and sin-gle-cell rNA-seq technologies,single-cell lineage trac-ing provides new opportunities to interrogate both cell states and lineage *** the past few years,many strategies to achieve lineage tracing at single-cell resolution have been developed,and three of them(in-tegration barcodes,polylox barcodes,and CrISPr barcodes)are noteworthy as they are amenable in experimentally tractable *** the above strategies have been demonstrated in animal develop-ment and stem cell research,much care and effort are still required to implement these *** we review the development of single-cell lineage tracing,major characteristics of the cell barcoding strategies,applications,as well as technical considerations and limitations,providing a guide to choose or improve the single-cell barcoding lineage tracing.

关键词： single-cell lineage tracing integration barcodes polylox barcodes CrISPr barcodes

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rOS-responsive hydrogels with spatiotemporally sequential delivery of antibacterial and anti-inflammatory drugs for the repair of MrSA-infected wounds

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regenerative Biomaterials 2024年第1期3卷 119-131页

作者： Bowen Qiao Jiaxin Wang Lipeng Qiao Aziz Maleki Yongping Liang Baolin Guo Key Laboratory of Shaanxi Province for Craniofacial Precision medicine research College of StomatologyXi’an Jiaotong UniversityXi’an 710049China State Key Laboratory for Mechanical Behavior of Materials Frontier Institute of Science and TechnologyXi’an Jiaotong UniversityXi’an 710049China Zanjan Pharmaceutical Nanotechnology research center(ZPNrC) Zanjan 45139-56184Iran department of Orthopaedics The First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061People’s Republic of China

For the treatment of MrSA-infected wounds,the spatiotemporally sequential delivery of antibacterial and anti-inflammatory drugs is a promising *** this study,rOS-responsive HA-PBA/PVA(HPA)hydrogel was prepared by phenylborate ester bond cross-linking between hyaluronic acid-grafted 3-amino phenylboronic acid(HA-PBA)and polyvinyl alcohol(PVA)to achieve spatiotemporally controlled release of two kinds of drug to treat MrSA-infected *** hydrophilic antibiotic moxifloxacin(M)was directly loaded in the *** hydrophobic curcumin(Cur)with anti-inflammatory function was first mixed with Pluronic F127(PF)to form Cur-encapsulated PF micelles(Cur-PF),and then loaded into the HPA *** to the different hydrophilic and hydrophobic nature of moxifloxacin and Cur and their different existing forms in the HPA hydrogel,the final HPA/M&Cur-PF hydrogel can achieve different spatiotemporally sequential delivery of the two *** addition,the swelling,degradation,self-healing,antibacterial,anti-inflammatory,antioxidant property,and biocompatibility of hydrogels were ***,in the MrSA-infected mouse skin wound,the hydrogel-treated group showed faster wound closure,less inflammation and more collagen *** experiments further confirmed that the hydrogel promoted better repair by reducing inflammation(TNF-a)and promoting vascular(VEGF)*** conclusion,this HPA/M&CurPF hydrogel that can spatiotemporally sequential deliver antibacterial and anti-inflammatory drugs showed great potential for the repair of MrSA-infected skin wounds.

关键词： MrSA-infected wounds spatiotemporally sequential delivery antibacterial anti-inflammatory

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Vascularization ability of glioma stem cells in different three-dimensional microenvironments

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regenerative Biomaterials 2024年第1期3卷 34-43页

作者： Xuanzhi Wang Tao Xu Chaoshi Niu department of Neurosurgery The First Affliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui230036China department of Neurosurgery Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengdu 610072People's Republic of China center for Bio-intelligent Manufacturing and Living Matter Bioprinting Research Institute of Tsinghua University in ShenzhenTsinghua UniversityShenzhen 518057People's Republicof China

Glioblastoma(GBM)is among the most common and aggressive adult central nervous system *** prominent charac-teristic of GBM is the presence of abnormal microvessels.A significant correlation between angiogenesis and prognosis has been *** reconstructing this neovascula-rization and tumor microenvironment through personalized in vitro disease models presents a significant ***,it is crucial to develop new anti-angiogenic therapies for *** this study,3d bioprinted glioma stem cell(GSC)-laden hydrogel scaffolds,hybrid Gsc hydrogels and ceil-free hydrogel scaffolds were manufactured to investigate the vas-cularization ability of GsCs in varying 3d microenvironments.

关键词： 3d bioprinting xenograft tumors GSC-laden hydrogel scaffold glioblastoma angiogenesis

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Pitfalls and promises of bile duct alternatives:There is plenty of room in the regenerative surgery

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World Journal of Gastroenterology 2023年第30期29卷 4701-4705页

作者： Ilya d Klabukov denis S Baranovskii Peter V Shegay Andrey d Kaprin department of regenerative medicine National Medical Research Radiological Center of the Ministry of Health of the Russian FederationObninsk 249036Russia center for Innovative radiological and regenerative Technologies National Medical Research Radiological Center of the Ministry of Health of the Russian FederationObninsk 249036Russia

Current abdominal surgery has several approaches for biliary ***,the creation of functional and clinically applicable bile duct substitutes still represents an unmet *** the paper by Miyazawa and colleagues,approaches to the creation of bile duct alternatives were summarized,and the reasons for the lack of development in this area were *** history of bile duct surgery since the nineteenth century was also traced,leading to the conclusion that the use of bioabsorbable materials holds promise for the creation of bile duct substitutes in the *** suggest three ideas that may stimulate progress in the field of bile duct substitute ***,a systematic analysis of the causative factors leading to failure or success in the creation of bile duct substitutes may help to develop more effective ***,the regeneration of a bile duct is delicately balanced between epithelialization and subsequent submucosal maturation within limited time frames,which may be more apparent when using quantitative models to estimate ***,the utilization of the organism’s endogenous regeneration abilities may enhance the creation of bile duct *** are convinced that an interdisciplinary approach,including quantitative methods,machine learning,and deep retrospective analysis of the causes that led to success and failure in studies on the creation of bile duct substitutes,holds great ***,more attention should be directed towards the balance of epithelialization and submucosal maturation rates,as well as induced *** ideas deserve further investigation to pave the way for bile duct restoration with physiologically relevant outcomes.

关键词： Bile duct alternative Bile duct substitute regenerative medicine regene rative surgery Theoretical surgery Quantitative human physiology

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Practical bioinformatics pipelines for single-cell rNA-seq data analysis

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Biophysics reports 2022年第3期8卷 158-169页

作者： Jiangping He Lihui Lin Jiekai Chen center for Cell Lineage and Atlas (CCLA) Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory) Key Laboratory of regenerative Biology of the Chinese Academy of Sciences and Guangdong Provincial Key Laboratory of Stem Cell and regenerative medicine Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences

Single-cell rNA sequencing(sc rNA-seq) is a revolutionary tool to explore cells. With an increasing number of sc rNA-seq data analysis tools that have been developed, it is challenging for users to choose and compare their performance. Here, we present an overview of the workflow for computational analysis of sc rNA-seq data. We detail the steps of a typical sc rNA-seq analysis, including experimental design, pre-processing and quality control, feature selection, dimensionality reduction, cell clustering and annotation, and downstream analysis including batch correction, trajectory inference and cell–cell communication. We provide guidelines according to our best practice. This review will be helpful for the experimentalists interested in analyzing their data, and will aid the users seeking to update their analysis pipelines.

关键词： Single-cell rNA sequencing (scrNA-seq) scrNA-seq analysis Practical bioinformatics pipeline

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An overview of autophagy in the differentiation of dental stem cells

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BIOCELL 2024年第1期48卷 47-64页

作者： XITONG ZHAO TIANJUAN JU XINWEI LI CHANGFENG LIU LULU WANG LI-AN WU State Key Laboratory of Oral&Maxillofacial reconstruction and regeneration National Clinical Research Center for Oral DiseasesShaanxi Clinical Research Center for Oral DiseasesDepartment of Pediatric DentistrySchool of StomatologyThe Fourth Military Medical UniversityXi’an710032China

dental stem cells(dSCs)have attracted significant interest as autologous stem cells since they are easily accessible and give a minimal immune *** properties and their ability to both maintain self-renewal and undergo multi-lineage differentiation establish them as key players in regenerative *** many regulatory factors determine the differentiation trajectory of dSCs,prior research has predominantly been based on genetic,epigenetic,and molecular *** evidence suggests that dSC differentiation can also be influenced by autophagy,a highly conserved cellular process responsible for maintaining cellular and tissue homeostasis under various stress *** comprehensive review endeavors to elucidate the intricate regulatory mechanism and relationship between autophagy and dSC *** achieve this goal,we dissect the intricacies of autophagy and its ***,we elucidate its pivotal roles in impacting dSC differentiation,including osteo/odontogenic,neurogenic,and angiogenic ***,we reveal the regulatory factors that govern autophagy in dSC lineage commitment,including scaffold materials,pharmaceutical cues,and the extrinsic *** implications of this review are far-reaching,underpinning the potential to wield autophagy as a regulatory tool to expedite dSC-directed differentiation and thereby promote the application of dSCs within the realm of regenerative medicine.

关键词： dental stem cells Cell differentiation Autophagy Mitophagy Autophagy regulation

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