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3D-printed tissue repair patch combining mechanical support and magnetism for controlled skeletal muscle regeneration

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Bio-Design and Manufacturing 2022年第2期5卷 249-264页

作者： Xiaocheng Wang ruibo zhao Jian Wang Xinghuan Li Lijuan Jin Wenyu Liu Lifang Yang Yonghua Zhu Zhikai Tan College of Biology Hunan UniversityChangsha 410082China Department of Orthopaedics Xiangya HospitalCentral South UniversityChangsha 410008China Key Laboratory of Carcinogenesis and Cancer Invasions of Ministry of Education School of Basic Medicine ScienceCancer Research InstituteCentral South UniversityChangsha 410008China

Physical forces,such as magnetic and mechanical stimulation,are known to play a significant role in the regulation of cell response.In the present study,a biomimetic regeneration patch was fabricated using E-jet 3 D printing,which integrates mechanical and magnetic stimulation in a biocompatible"one-pot reaction"strategy when combined with a static magnetic field(SMF).The magneto-based therapeutic regeneration patch induced myoblasts to form aligned and multinucleated myotubes,regulated the expression of myogenic-related genes,and activated the p38αmitogen-activated protein kinase pathway via the initiation of myogenic differentiation.To validate the efficiency of the proposed strategy,the regeneration patch was implanted into mice and exposed to a suitable SMF,which resulted in significantly enhanced in vivo skeletal muscle regeneration.The findings demonstrated that appropriate external physical stimulation provides a suitable biophysical microenvironment that is conducive to tissue regeneration.The method used in the present study represents a promising technique to induce the regeneration of damaged skeletal muscle tis sue.

关键词： Functional biomaterials Magnetic actuation Myogenic differentiation Skeletal muscle regeneration 3D printing

Fabrication of glycidyl methacrylate-modified silk fibroin/poly(L-lactic acid-co-ε-caprolactone)-polyethylene glycol diacrylate hybrid 3D nanofibrous scaffolds for tissue engineering

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Frontiers of Materials Science 2023年第2期17卷 79-91页

作者： Yongyong Fan Anlin Yin Yunhuan Li Qi Gu Yan Zhou Junlong Zhou ruibo zhao Kuihua Zhang Institute of Smart Biomaterials School of Materials Science and Engineering and Zhejiang-Mauritius Joint Research Center for Biomaterials and Tissue EngineeringZhejiang Sci-Tech UniversityHangzhou 310018China College of Materials and Textile Engineering Nanotechnology Research InstituteJiaxing UniversityJiaxing 314001China

In order to provide a biomimetic natural extracellular matrix microenvironment with excellent mechanical capacity for tissue regeneration,a novel porous hybrid glycidyl methacrylate-modified silk fibroin/poly(L-lactic acid-co-ε-caprolactone)–polyethylene glycol diacrylate(SFMA/P(LLA-CL)–PEGDA)hybrid three-dimensional(3D)nanofibrous scaffolds was successfully fabricated through the combination of 3D nanofibrous platforms and divinyl PEGDA based photocrosslinking,and then further improved water resistance by ethanol vapor post-treatment.Scanning electron microscopy and micro-computed tomography results demonstrated significant PEGDA hydrogel-like matrices bonded nanofibers,which formed a 3D structure similar to that of“steel bar(nanofibers)‒cement(PEGDA)”,with proper pore size,high porosity,and high pore connectivity density.Meanwhile,the hybrid 3D nanofibrous scaffolds showed outstanding swelling properties as well as improved compressive and tensile properties.Furthermore,these hybrid 3D nanofibrous scaffolds could provide a biocompatible microenvironment,capable of inducing the material‒cell hybrid and regulating human umbilical vein endothelial cells proliferation.They thus present significant potential in tissue regeneration.

关键词： hybrid 3D nanofibrous scaffold silk fibroin tissue engineering human umbilical vein endothelial cell

Ovalbumin-loaded paramagnetic nano-triangles for enhanced dendritic cell stimulation,T_(1)-MR imaging,and antitumor immunity

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Journal of Materials Science & Technology 2023年第17期148卷 123-137页

作者： Yike Hou Zhe Tang Jabeen Farheen Madiha Saeed Lijia Luo Wenzi Ren Dandan Luo Asim Mushtaq ruibo zhao Jian Ge Zhangsen Yu Yao Li M.Zubair Iqbal Xiangdong Kong Institute of Smart Biomedical Materials School of Materials Science and EngineeringZhejiang Sci-Tech UniversityHangzhou 310018China State Key Laboratory of Drug Research&Center of Pharmaceutics Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Cixi Institute of Biomedical Engineering CAS Key Laboratory of Magnetic Materials and DevicesKey Laboratory of Additive Manufacturing Materials of Zhejiang ProvinceNingbo Institute of Materials Technology and EngineeringChinese Academy of SciencesNingbo 315201China Department of Materials Imperial College LondonLondon SW72AZUK College of Life Sciences China Jiliang UniversityHangzhou 310018China Laboratory of Nanomedicine Medical Science Research CenterSchool of MedicineShaoxing UniversityShaoxing 312000China

Vaccine-based cancer immunotherapy has demonstrated a significant potential for cancer treatment in clinics.Although the efficiencies of vaccines are limited,they can be enhanced by a well-designed antigen delivery system that promotes sufficient antigen presentation of dendritic cells(DCs)for initiating high T cell immunity.Herein,antigen-loaded manganese oxide(Mn_(3)O_(4))triangular-shaped ultrasmall nanoparti-cles were prepared to stimulate DC-based immunotherapy under the guidance of T_(1)magnetic resonance imaging.The FDA-approved triblock copolymer Pluronic^(■)F-68 wasused not onlyto transferthe phase from hydrophobic to hydrophilic but also to enrich antigen loading and improve the biocompatibility of the prepared nanoparticles.Ovalbumin(OVA),a model antigen,was adsorbed on the surface of polymer-coated nanoparticles through electrostatic interaction to form Mn_(3)O_(4)@PF68-OVA nanoparticle-antigen complexes to stimulate DC-based immunization and antigen-specific T cell immunity.The Mn_(3)O_(4)@PF68-OVA nanovaccine(NV)induces negligible toxicity effects against 4T1 and bone marrow-derived dendritic cells(BMDCs)by conventional methods supports the proliferation of intestine organoids,which are an innovative three-dimensional cytotoxicity evaluation system,thereby indicating their potential safety for in vivo cancer therapies.The designed paramagnetic nanovaccine possessed excellent OVA delivery to dendritic-regulated antigen-specific T cells in vitro by stimulating the maturation level of BMDCs.In ad-dition,Mn_(3)O_(4)@PF68-OVA NVs enhance immunity in vivo by increasing the T-cells and M1 macrophages,which suggests improved immunity.Excitingly,vaccination with Mn_(3)O_(4)@PF68-OVA offer complete pro-tection in the prophylactic group and significant tumor inhibition in the therapeutic group against B16-OVA tumor.In addition,the designed nanovaccine demonstrated high T_(1)-MR imaging in the tumor,fur-ther justifying enhanced tumor accumulation and capability to real-time monitor the treatment proce-dure.This

关键词： Ovalbumin Nanovaccine Antigen delivery Magnetic resonance imaging Contrast agent Cancer immunotherapy

考虑老化影响的SSPC功率管热模型自适应在线修正方法

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电源学报 2024年第1期22卷 171-178页

作者：钱叶彤王莉赵瑞博南京航空航天大学多电飞机电气系统工信部重点实验室南京211000

固态功率控制器SSPC(solid-state power controller)中功率管的结温监测对SSPC的可靠性有至关重要的作用,热模型法因其无需直接接触测量且方法简单而被广泛使用。然而,功率芯片的老化会导致热路径的退化,器件的结壳热阻抗增加,使实际结... 详细信息

固态功率控制器SSPC(solid-state power controller)中功率管的结温监测对SSPC的可靠性有至关重要的作用,热模型法因其无需直接接触测量且方法简单而被广泛使用。然而,功率芯片的老化会导致热路径的退化,器件的结壳热阻抗增加,使实际结温远远超过热网络模型的估计值,导致对器件健康状态的乐观估计。焊料层疲劳失效被认为是SSPC功率管老化失效的主要原因之一。因此,在SSPC的寿命周期中实时监测器件的老化状态,并对功率管的热模型进行自适应在线修正,通过测量不受焊料层退化影响的热敏参数来计算热阻作为更新依据,将热阻信息关联焊料层老化状态来更新热模型。所提方法可在不影响SSPC正常工作的前提下,实时修正热模型,实验结果验证了方法的有效性。

关键词：热模型修正固态功率控制器结温 MOSFET 老化

通过整合的生物信息学方法鉴定H和L型血管内皮细胞中的ceRNA网络

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中南大学学报（医学版） 2024年第4期49卷 562-577页

作者：刘志阮哲龙海涛赵瑞波朱勇林涨源陈鹏赵树山中南大学湘雅医院骨科长沙410008 国家老年疾病临床医学研究中心(湘雅医院) 长沙410008

目的:H型血管是一种骨特异性微血管亚型(CD31hiEmcnhi),在成血管-成骨耦联机制中具有重要的调节作用。研究报道H和L型血管在骨骼生理和病理条件下发挥不同的作用,它们之间的遗传差异仍有待阐明。本研究旨在通过整合的生物信息学方法构建... 详细信息

目的:H型血管是一种骨特异性微血管亚型(CD31hiEmcnhi),在成血管-成骨耦联机制中具有重要的调节作用。研究报道H和L型血管在骨骼生理和病理条件下发挥不同的作用,它们之间的遗传差异仍有待阐明。本研究旨在通过整合的生物信息学方法构建H和L型血管内皮细胞中关键差异表达(differential expression,DE)基因的竞争性内源RNA(competitive endogenous RNA,ceRNA)网络。方法:从ArrayExpress和基因表达综合(Gene Expression Omnibus,GEO)数据库中下载相关原始数据,通过Limma R-Bioconductor包筛选H和L型血管间的DE lncRNAs、DE miRNAs和DE mRNAs,构建总ceRNA网络,随后根据蛋白质相互作用(protein-protein interaction,PPI)网络筛选出上调和下调的关键基因,以此精细化ceRNA网络并对关键基因进行富集分析。最后,通过流式细胞术和real time RT-PCR进行随机验证。结果:共鉴定出1 761个DE mRNAs、187个DE lncRNAs和159个DE miRNAs,通过相互作用关系构建总ceRNA网络;通过PPI网络筛选出6个上调(Itga5、Kdr、Tjp1、Pecam1、Cdh5、Ptk2)和2个下调(Csf1r、Il10)的关键基因,并以此构建关键基因相关的ceRNA亚网络。上调的关键基因主要富集在血管生成与血管凋亡的负调控;流式细胞术和real-time RT-PCR的结果与生物信息学分析结果一致。结论:本研究根据所筛选的关键基因提出上调和下调的H型和L型血管内皮细胞相关的ceRNA网络,为H型和L型血管内皮细胞在骨代谢中的调控机制提供了新见解。

关键词：骨骼血管 H型血管内皮细胞 ceRNA网络生物信息学

骶骨骨折固定后腹直肌外侧入路神经松解术治疗合并的骶丛神经损伤的效果分析

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中华创伤骨科杂志 2024年第3期26卷 215-221页

作者：梁子霖曾敏朱勇赵瑞波龙海涛成亮林涨源中南大学湘雅医院骨科长沙410008

目的探讨骶骨骨折固定后腹直肌外侧入路神经松解术治疗合并的骶丛神经损伤的效果。方法回顾性分析2022年5月至2023年至5月期间中南大学湘雅医院骨科收治的10例骶骨骨折固定后仍合并骶丛神经损伤患者资料。男2例,女8例;年龄16.5(15.0,26... 详细信息

目的探讨骶骨骨折固定后腹直肌外侧入路神经松解术治疗合并的骶丛神经损伤的效果。方法回顾性分析2022年5月至2023年至5月期间中南大学湘雅医院骨科收治的10例骶骨骨折固定后仍合并骶丛神经损伤患者资料。男2例,女8例;年龄16.5(15.0,26.3)岁。患者受伤时明确诊断为骶骨骨折伴骶丛神经损伤,骶骨骨折Denis分型:Ⅱ区7例,Ⅲ区3例;骶丛神经损伤部位:L41例,L58例,S17例,S22例。伤后2周内均经后方入路行骨折复位内固定治疗,术后患者仍持续存在骶丛神经损伤表现,并通过CT、磁共振成像及神经肌电图明确诊断。内固定后(4.0±2.3)个月所有患者采用腹直肌外侧入路神经松解术治疗。记录患者的手术时间、术中出血量、住院时间、末次随访时Gibbons神经损害评分及神经功能恢复情况等。结果10例患者的手术时间为(112.0±21.5)min,术中出血量为(215.0±91.3)mL,住院时间为7.0(6.0,8.5)d。术中发现骶丛神经受压9例(骨折移位致神经受压牵拉6例,软组织瘢痕粘连致神经卡压3例),神经根撕脱损伤1例。术中无其他并发症发生。10例患者术后获(9.2±2.3)个月随访。末次随访时10例患者的Gibbons神经损害评分由术前3.0(3.0,3.3)分改善至1.0(1.0,2.0)分;英国医学研究理事会肌力分级由术前的0.0(0.0,1.3)级恢复至3.5(2.8,4.0)级(其中M5级1例,M4级4例,M3级4例,M2级1例),差异均有统计学意义(P<0.05)。结论对于骶骨骨折固定后仍合并的骶丛神经损伤,腹直肌外侧入路神经松解术的治疗效果良好,腹直肌外侧入路是一种有效且安全的手术入路。

关键词：骶骨骨折腰骶丛腹直肌外侧入路神经松解术

硼替佐米治疗儿童复发/难治性B系急性淋巴细胞白血病研究进展

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国际儿科学杂志 2024年第1期51卷 29-33页

作者：王玉姣赵睿博郝良纯中国医科大学附属盛京医院小儿血液科沈阳110004 中国医科大学第二临床学院沈阳110004

急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)是儿童最常见的恶性肿瘤,通常预后良好,但儿童复发/难治性ALL的预后较差,大剂量再诱导化疗和造血干细胞移植成为这类患者的替代治疗。硼替佐米作为初代蛋白酶体抑制剂,获批用于治... 详细信息

急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)是儿童最常见的恶性肿瘤,通常预后良好,但儿童复发/难治性ALL的预后较差,大剂量再诱导化疗和造血干细胞移植成为这类患者的替代治疗。硼替佐米作为初代蛋白酶体抑制剂,获批用于治疗多发性骨髓瘤和套细胞淋巴瘤。近年来一些临床研究证实,硼替佐米可以与多种化疗药物联合应用,安全且有效地治疗儿童复发/难治性ALL,提高此类患者的完全缓解率和生存率。该文综述硼替佐米对ALL的作用机制及硼替佐米联合化疗在儿童复发/难治性ALL中的临床研究进展和安全性。

关键词：儿童急性淋巴细胞白血病硼替佐米

仿生矿化透明质酸钠复合材料的制备及其性能分析

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浙江理工大学学报（自然科学版） 2024年第3期51卷 292-299页

作者：陈思颖谢番赵瑞波孔祥东浙江理工大学材料科学与工程学院杭州310018

为了提升透明质酸钠(Sodium hyaluronate,SH)的力学性能,采用仿生矿化方法,将磷酸钙寡聚体(Calcium phosphate oligomers,CPO)与SH复合形成透明质酸钠复合材料(SH-CPO),对SH-CPO的形貌、结构、流变学特性及压缩性能进行了测试与表征。... 详细信息

为了提升透明质酸钠(Sodium hyaluronate,SH)的力学性能,采用仿生矿化方法,将磷酸钙寡聚体(Calcium phosphate oligomers,CPO)与SH复合形成透明质酸钠复合材料(SH-CPO),对SH-CPO的形貌、结构、流变学特性及压缩性能进行了测试与表征。结果表明:SH不仅与CPO具有良好的相互作用,能形成内部结构连续的复合材料,还能诱导CPO发生从无定形到结晶相的转变;在SH与CPO的质量比为1∶1~1∶10范围内,随着CPO投料比例的增加,制备的SH-CPO复合材料的黏度得到提升,压缩强度可达到53.5 MPa。该研究制备的SH-CPO复合材料具有良好的力学性能,在生物医学材料领域中具有良好的应用潜力。

关键词：仿生矿化透明质酸钠磷酸钙寡聚体复合材料力学性能

High-throughput fluorescent screening of thioredoxin reductase inhibitors to inhibit Mycobacterium tuberculosis

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Chinese Chemical Letters 2024年第3期35卷 358-362页

作者： Fei Yan Xin zhao ruibo Li Xiuyan Han Qiulong Yan Lei Feng Xiulan Xin Jingnan Cui Xiaochi Ma Second Affiliated Hospital Dalian Medical UniversityDalian 116044China State Key Laboratory of Fine Chemicals Dalian University of TechnologyDalian 116024China Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical UniversityXuzhou 221004China School of Chemistry and Chemical Engineering Henan Normal UniversityXinxiang 453007China College of Bioengineering Beijing PolytechnicBeijing 100029China

Tuberculosis(TB)is a chronic infectious disease,which is caused by the pathogen Mycobacterium tuberculosis(Mtb)and reemerged as a global health risk with a significant proportion of multi-drug resistant and extensively drug resistant TB cases.It is very urgent to find some novel high-confidence drug targets in Mtb for discovering the effective anti-TB agents.Thioredoxin reductase(TrxR)has been identified to be a highly viable target for anti-TB drugs for its important role in protecting the pathogen from thiol-specific oxidizing stress,regulating intracellular dithiol/disulfide homeostasis and DNA replication and repair.In the present work,a near-infrared(NIR)fluorescent probe DDAT was developed for the detection of TrxR activity and used to high-throughput screen the TrxR inhibitors from natural products.Two screened TrxR inhibitors from Sappan Lignum and microbial metabolites that were further used to inhibit Mycobacterium tuberculosis.All the results indicate that DDAT is a practical fluorescent molecular tool for the discovery of potential anti-TB drugs.

关键词： Thioredoxin reductase NIR fluorescent probe Fluorescence imaging High-throughput screening inhibitors Inhibit Mycobacterium tuberculosis