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Thread-structural microneedles loaded with engineered exosomes for annulus fibrosus repair by regulating mitophagy recovery and extracellular matrix homeostasis

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Bioactive Materials 2024年第7期37卷 1-13页

作者： Shaojun Hu Meng Zhu Hongyuan Xing Yucheng Xue Jun Li Zhan Wang Zhou Zhu Miaojie Fang Zilong Li Jianbin Xu Yong He Ning Zhang Department of Orthopedic Surgery The Second Affiliated HospitalZhejiang University School of MedicineHangzhou CityZhejiang ProvincePR China Orthopedics Research Institute of Zhejiang University Hangzhou CityZhejiang ProvincePR China Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province Hangzhou CityZhejiang ProvincePR China Clinical Research Center of Motor System Disease of Zhejiang Province PR China State Key Laboratory of Fluid Power and Mechatronic Systems College of Mechanical EngineeringZhejiang UniversityHangzhou310027PR China Department of Orthopaedics The First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouZhejiang ProvincePR China

Low back pain is among the most grave public health concerns worldwide and the major clinical manifestation of intervertebral disc degeneration(IVDD).The destruction of annulus fibrosus(AF)is the primary cause of IVDD.A sustainable and stable treatment system for IVDD is lacking because of the special organizational structure and low nutrient supply of *** here found that IVDD results in the impaired mitochondrial function of AF tissue,and mitochondrial autophagy(mitophagy)plays a protective role in this *** therefore reported a thread-structural microneedle(T-MN)matching the ring structure of *** on the adsorption effect of laminin,our T-MN could load with bone marrow mesenchymal stem cell-derived exosomes to envelope the regulating mitophagy microRNA(miRNA 378),named as T-MN@EXO@miR􀀀*** general,we offered in situ locking in the defect site of AF to prevent nucleus pulposus leakage and promoted AF *** design of the thread structure was aimed at bionically matching the layered AF structure,thereby providing stronger *** T-MN@EXO@miR􀀀378 effectively attached to AF and slowly released therapeutic engineered exosomes,and prevented IVDD progression by restoring mitophagy,promoting AF cell proliferation and migration,and inhibiting the pathological remodeling of the extracellular *** functional system can be used as an excellent tool for sustained drug release and has a certain prospect in substituting the conventional treatment of IVDD.

关键词： Intervertebral disc degeneration Microneedle Exosomes annulus fibrosus Mitophagy

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Design principles in mechanically adaptable biomaterials for repairing annulus fibrosus rupture:A review

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Bioactive Materials 2024年第1期31卷 422-439页

作者： Dan Zhou Hongmei Liu Zhaomin Zheng Decheng Wu Guangdong Provincial Key Laboratory of Advanced Biomaterials Department of Biomedical EngineeringSouthern University of Science and TechnologyShenzhen518055China Department of Spine Surgery The First Affiliated HospitalSun Yat-Sen UniversityGuangzhou510080China Pain Research Center Sun Yat-Sen UniversityGuangzhou 510080China

annulus fibrosus(AF)plays a crucial role in the biomechanical loading of intervertebral disc(IVD).AF is difficult to self-heal when the annulus tears develop,because AF has a unique intricate structure and biologic milieu in *** engineering is promising for repairing AF rupture,but construction of suitable mechanical matching devices or scaffolds is still a grand *** deeply know the varied forces involved in the movement of the native annulus is highly beneficial for designing biomimetic scaffolds to recreate the AF *** this review,we overview six freedom degrees of forces and adhesion strength on AF ***,we summarize the mechanical modalities to simulate related forces on AF and to assess the characteristics of *** finally outline some current advanced techniques to develop mechanically adaptable biomaterials for AF rupture repair.

关键词： annulus fibrosus Forces Mechanical matching High tough High adhesion

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A multifunctional scaffold that promotes the scaffold-tissue interface integration and rescues the ROS microenvironment for repair of annulus fibrosus defects

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Bioactive Materials 2024年第11期41卷 257-270页

作者： Runze Zhao Feng Han Qifan Yu Zhuang Zhu Zhengdong Tu Tingting Xia Bin Li Medical 3D Printing Center Orthopedic InstituteDepartment of Orthopedic SurgeryThe First Affiliated HospitalMOE Key Laboratory of Geriatric Diseases and ImmunologySchool of Biology and Basic Medical SciencesSuzhou Medical CollegeSoochow UniversitySuzhouJiangsu215000China Center of Translational Medicine and Clinical Laboratory The Fourth Affiliated Hospital to Soochow UniversitySuzhou215028China Division of Spine Surgery Department of Orthopedic SurgeryNanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing210000China Second Department of Orthopaedics Suzhou Kowloon HospitalShanghai Jiaotong University Medical SchoolSuzhou215127China Institute of Clinical Medicine Research Suzhou HospitalAffiliated Hospital of Medical SchoolNanjing UniversitySuzhou215153China Collaborative Innovation Center of Hematology Soochow UniversitySuzhouJiangsu215000China

Due to the limited self-repair ability of the annulus fibrosus (AF), current tissue engineering strategies tend to use structurally biomimetic scaffolds for AF defect repair. However, the poor integration between implanted scaffolds and tissue severely affects their therapeutic effects. To solve this issue, we prepared a multifunctional scaffold containing loaded lysyl oxidase (LOX) plasmid DNA exosomes and manganese dioxide nanoparticles (MnO2 NPs). LOX facilitates extracellular matrix (ECM) cross-linking, while MnO2 NPs inhibit excessive reactive oxygen species (ROS)-induced ECM degradation at the injury site, enhancing the crosslinking effect of LOX. Our results revealed that this multifunctional scaffold significantly facilitated the integration between the scaffold and AF tissue. Cells were able to migrate into the scaffold, indicating that the scaffold was not encapsulated as a foreign body by fibrous tissue. The functional scaffold was closely integrated with the tissue, effectively enhancing the mechanical properties, and preventing vascular invasion, which emphasized the importance of scaffold-tissue integration in AF repair.

关键词： annulus fibrosus Scaffold-tissue integration Lysyl oxidase Reactive oxygen species regulation Manganese dioxide nanoparticles

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TGF-β1-supplemented decellularized annulus fibrosus matrix hydrogels promote annulus fibrosus repair

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Bioactive Materials 2023年第1期19卷 581-593页

作者： Qiang Wei Dachuan Liu Genglei Chu Qifan Yu Zhao Liu Jiaying Li Qingchen Meng Weishan Wang Fengxuan Han Bin Li Department of Orthopaedic Surgery Orthopaedic InstituteThe First Affiliated HospitalSuzhou Medical CollegeSoochow UniversitySuzhouJiangsuChina Department of Orthopaedic Surgery The First Affiliated HospitalShihezi University School of MedicineShiheziXinjiangChina Collaborative Innovation Center of Hematology Soochow UniversitySuzhouJiangsuChina

annulus fibrosus(AF)repair remains a challenge because of its limited self-healing *** repair strategies combining scaffolds and growth factors show great promise in AF *** the unique and beneficial characteristics of decellularized extracellular matrix(ECM)in tissue repair have been demonstrated,the poor mechanical property of ECM hydrogels largely hinders their applications in tissue *** the present study,we combined polyethylene glycol diacrylate(PEGDA)and decellularized annulus fibrosus matrix(DAFM)to develop an injectable,photocurable hydrogel for AF *** found that the addition of PEGDA markedly improved the mechanical strength of DAFM hydrogels while maintaining their porous *** growth factor-β1(TGF-β1)was further incorporated into PEGDA/DAFM hydrogels,and it could be continuously released from the *** in vitro experiments showed that TGF-β1 facilitated the migration of AF ***,PEGDA/DAFM/TGF-β1 hydrogels supported the adhesion,proliferation,and increased ECM production of AF *** vivo repair performance of the hydrogels was assessed using a rat AF defect *** results showed that the implantation of PEGDA/DAFM/TGF-β1 hydrogels effectively sealed the AF defect,prevented nucleus pulposus atrophy,retained disc height,and partially restored the biomechanical properties of *** addition,the implanted hydrogel was infiltrated by cells resembling AF cells and well integrated with adjacent AF *** summary,findings from this study indicate that TGF-β1-supplemented DAFM hydrogels hold promise for AF repair.

关键词： Decellularized matrix annulus fibrosus Hydrogel TGF-β1 Tissue repair

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Rabbit annulus fibrosus Cell Apoptosis Induced by Mechanical Overload via a Mitochondrial Apoptotic Pathway

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2010年第3期30卷 379-384页

作者：谢卯杨述华 Hein Latt Win 熊蠡茗黄吉军周建国 Department of Orthopaedics Union HospitalTongji Medical CollegeHuazhong University of Science and Technology

In order to investigate the apoptotic pathway of rabbit annulus fibrosus(AF) cells induced by mechanical overload,an experimental air-pressure model was established in this study to pressurize the rabbit AF cells in *** were randomly divided into five groups in which the cells were exposed to a continuous pressure of 1.1 MPa for different lengths of time(0,5,12,24 and 36 h).The cell proliferation and apoptosis were detected by cell counting kit-8(CCK-8) assay and flow cytometry;the alterations in mitochondrial membrane potential were measured by fluorescence microscopy and fluorescence spectrophotometer;the activities of caspase-8 and 9 were determined by *** results showed that after the cells were subjected to the pressure for 24 or 36 h,the cell proliferation was inhibited;the ratio of cell apoptosis was increased;the mitochondrial membrane potential was decreased;the activity of caspase-9 was enhanced;no activity changes were observed in *** results suggested that treatment with a pressure of 1.1 MPa for more than 24 h can lead to the proliferation inhibition and the apoptosis of rabbit AF cells in vitro,and the mitochondrial-dependent pathway is implicated in the pressure-induced AF cell apoptosis.

关键词： pressure annulus fibrosus apoptosis mitochondrial membrane potential caspase

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A novel rat tail disc degeneration model induced by static bending and compression

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Animal Models and Experimental Medicine 2021年第3期4卷 261-267页

作者： Yichao Ji Pengfei Zhu Linlin Zhang Huilin Yang Department of Orthopaedic Surgery The First Affiliated Hospital of Soochow UniversitySuzhouP.R.China

Background:A new rat tail intervertebral disc degeneration model was established to observe the morphologic and biologic changes of static bending and compression applied to the ***:In total,20 Sprague-Dawley rats with similar weight were randomly di-vided into 4 *** 1 served as a control group for a baseline assessment of normal *** 2 underwent a sham surgery,using an external device to bend the vertebrae of coccygeal *** 3 and 4 were the loaded groups,and exter-nal devices were instrumented to bend the spine with a compression level of 1.8 N and 4.5 N,*** resonance imaging(MRI),histological,and quanti-tative real-time PCR(qRT-PCR)analysis were performed on all animals on day 14 of the ***:Magnetic resonance imaging and histological results showed that the changes of intervertebral disc degeneration increased with the size of compression *** architecture disorganizations in nucleus pulposus and annulus fibro-sus were found on both of the convex and concave side in the groups of 1.8 N and 4.5 *** upregulation of MM-3,MM-13,and collagen 1-α1 mRNA expression and a downregulation of collagen 2-α1 and aggrecan mRNA expression were observed in the sham and loading *** changes were found between the loading groups,whereas the sham group showed similar results to the control ***:Static bending and compression could induce progressive disc degen-eration,which could be used for biologic study on disc degeneration promoted by static complex loading.

关键词： animal model annulus fibrosus bending and compression disc degeneration nucleus pulposus

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AFM observation of subfibrillar and fragmental structure of collagen from human lumbar intervertebral discs

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Progress in Natural Science:Materials International 1997年第3期 69-74页

作者：顾宁韦齐和潘维陆祖宏韦钰朱同银沈家维童明庆周士枋

An atomic force microscope (AFM) was used to image fibrillar and fragmental structures of human collagen from lumbar intervertebral discs. It is revealed that the characteristic 60-70 nm D-band consists of alternative ridges and grooves with ca. 3 nm height difference and that some globular grains ca. 200 nm in diameter are adhered to the fibrils. The length and diameter of collagen monomers of the isolated and decomposed samples are ca. 300 nm and ca. 1.5 nm, respectively. A comparison of topography of type II collagen in nucleus pulposus of young people with that of the aged has shown that one of the main causes for reducing the cushioning ability of old people is degeneration or reduction of type Ⅱ collagen. It is in accordance with to some clinical experiences.

关键词： atomic force microscope (AFM) collagen lumbar intervertebral disc nucleus pulposus annulus fibrosus

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