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Injectable hybrid inorganic nanoscaffold as rapid stem cell assembly template for cartilage repair

National Science Review 2022年第4期9卷 116-127页

作者： Shenqiang Wang Letao Yang Bolei Cai Fuwei Liu Yannan Hou Hua Zheng Fang Cheng Hepeng Zhang Le Wang Xiaoyi Wang Qianxin Lv Liang Kong Ki-Bum Lee Qiuyu Zhang Key Laboratory of Special Functional and Smart Polymer Materials of Ministry of Industry and Information Technology School of Chemistry and Chemical EngineeringNorthwestern Polytechnical University Xi'an Key Laboratory of Functional Organic Porous Materials School of Chemistry and Chemical EngineeringNorthwestern Polytechnical University Department of Chemistry and Chemical Biology Rutgers University Department of Biomedical Engineering Columbia University State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Oral Diseases Department of Oral and Maxillofacial SurgerySchool of StomatologyThe Fourth Military Medical University Research & Development Institute of Northwestern Polytechnical University in Shenzhen

cartilage injuries are o?ten devastating and most cannot be cured because of the intrinsically low regenerative capacity of cartilage tissues. Although stem-cell therapy has shown enormous potential for cartilage repair, the therapeutic outcome has been restricted by low survival rates and poor chondrocyte differentiation in vivo. Here, we report an injectable hybrid inorganic(IHI) nanoscaffold that facilitates fast assembly, enhances survival and regulates chondrogenic differentiation of stem cells. IHI nanoscaffolds that strongly bind to extracellular matrix(ECM) proteins assemble stem cells through synergistic 3 D cell–cell and cell–matrix interactions, creating a favorable physical microenvironment for stem-cell survival and differentiation in vitro and in vivo. Additionally, chondrogenic factors can be loaded into nanoscaffolds with a high capacity, which allows deep, homogenous drug delivery into assembled 3 D stem-cell-derived tissues for effective control over the soluble microenvironment of stem cells. The developed IHI nanoscaffolds that assemble with stem cells are injectable. They also scavenge reactive oxygen species and timely biodegrade for proper integration into injured cartilage tissues. Implantation of stem-cell-assembled IHI nanoscaffolds into injured cartilage results in accelerated tissue regeneration and functional recovery. By establishing our IHI nanoscaffold-templated 3 D stem-cell assembly method, we provide a promising approach to better overcoming the inhibitory microenvironment associated with cartilage injuries and to advance current stem-cell-based tissue engineering.

关键词： injectable nanoscaffold 3D cell culture tissue engineering cartilage repair stem-cell therapy

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Ultrasound augmenting injectable chemotaxis hydrogel for articular cartilage repair in osteoarthritis

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Chinese Chemical Letters 2021年第5期32卷 1759-1764页

作者： Hui Liu Xi Xiang Jianbo Huang Bihui Zhu Liyun Wang Yuanjiao Tang Fangxue Du Ling Li Feng Yan Lang Ma Li Qiu Department of Ultrasound Laboratory of Ultrasound Imaging DrugWest China HospitalSichuan UniversityChengdu 610041China Department of Ultrasound The Affiliated Hospital of Southwest Medical UniversityLuzhou 646000China

The increasing incidence of osteoarthritis(OA) seriously affects life quality,posing a huge socioeco nomic *** engineering technology has become a hot topic in articular cartilage repair as one of the key treatment methods to alleviate ***,one of the most commonly used scaffold materials,ca n provide a good extracellular matrix microenvironment fo r seed cells such as bone marrow mesenchymal stem cells(BMSCs),which can promote cartilage ***,the low homing rate of stem cells severely limits their role in promoting articular cartilage *** mal cell-derived factor-1α(SDF-1α) plays a crucial role in the activatio n,mobilization,homing,and migration of *** rein,a novel injectable chemotaxis hydrogel,composed of chitosan-based injectable hydrogel and embedding SDF-1α-loaded nanodroplets(PFP@NDs-PEG-SDF-1α) was designed and *** ultrasound was then used to augment the injectable chemotaxis hydrogel and promote the homing migration of BMSCs for OA cartilage *** effect of ultrasound augmenting injectable PFP@NDs-PEG-SDF-1α/hydrogel on the migration of BMSCs was verified in vitro and in vivo,which re markably promotes stem cell homing and the repair of cartilage in the OA ***,the treatment strategy of ultrasound augmenting injectable chemotaxis hydrogel has a bright potential for OA articular cartilage repair.

关键词： SDF-la Injectable hydrogel Ultrasound Osteoarthritis cartilage repair

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“Genetic scissors”CRISPR/Cas9 genome editing cutting-edge biocarrier technology for bone and cartilage repair

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Bioactive Materials 2023年第4期22卷 254-273页

作者： Chao Li Yawei Du Tongtong Zhang Haoran Wang Zhiyong Hou Yingze Zhang Wenguo Cui Wei Chen Department of Orthopaedics The Third Hospital of Hebei Medical UniversityOrthopaedic Research Institution of Hebei ProvinceNHC Key Laboratory of Intelligent Orthopaedic EquipmentNo.139 Ziqiang RoadShijiazhuang050051PR China Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint DiseasesShanghai Institute of Traumatology and OrthopaedicsRuijin HospitalShanghai Jiao Tong University School of Medicine197 Ruijin 2nd RoadShanghai200025PR China

CRISPR/Cas9 is a revolutionary genome editing technology with the tremendous advantages such as precisely targeting/shearing ability,low cost and convenient operation,becoming an efficient and indispensable tool in biological *** a disruptive technique,CRISPR/Cas9 genome editing has a great potential to realize a future breakthrough in the clinical bone and cartilage repairing as *** review highlights the research status of CRISPR/Cas9 system in bone and cartilage repair,illustrates its mechanism for promoting osteogenesis and chondrogenesis,and explores the development tendency of CRISPR/Cas9 in bone and cartilage repair to overcome the current limitations.

关键词： CRISPR/Cas9 Genome editing Bone repair cartilage repair

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O-alg-THAM/gel hydrogels functionalized with engineered microspheres based on mesenchymal stem cell secretion recruit endogenous stem cells for cartilage repair

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Bioactive Materials 2023年第10期28卷 255-272页

作者： Yucong Li Linlong Li Ming Wang Boguang Yang Baozhen Huang Shanshan Bai Xiaoting Zhang Nan Hou Haixing Wang Zhengmeng Yang Chong Tang Ye Li Wayne Yuk-Wai Lee Lu Feng Micky D.Tortorella Gang Li Stem Cells and Regenerative Medicine Laboratory Li Ka Shing Institute of Health SciencesThe Chinese University of Hong KongPrince of Wales HospitalShatinHong Kong Special Administrative Region of China Musculoskeletal Research Laboratory Department of Orthopaedics&TraumatologyFaculty of MedicineThe Chinese University of Hong KongPrince of Wales HospitalShatinHong Kong Special Administrative Region of China The CUHK-ACC Space Medicine Centre on Health Maintenance of Musculoskeletal System The Chinese University of Hong Kong Shenzhen Research InstituteShenzhenPR China Department of Orthopaedics Peking University Shougang HospitalBeijingPR China Department of Rehabilitation Sciences Hong Kong Polytechnic UniversityHong Kong Special Administrative Region of China Guangzhou Institutes of Biomedicine and Health Chinese Academy of SciencesGuangzhouChina

Lacking self-repair abilities,injuries to articular cartilage can lead to cartilage degeneration and ultimately result in *** engineering based on functional bioactive scaffolds are emerging as promising approaches for articular cartilage regeneration and *** the use of cell-laden scaffolds prior to implantation can regenerate and repair cartilage lesions to some extent,these approaches are still restricted by limited cell sources,excessive costs,risks of disease transmission and complex manufacturing *** approaches through the recruitment of endogenous cells offer great promise for in situ articular cartilage *** this study,we propose an endogenous stem cell recruitment strategy for cartilage *** on an injectable,adhesive and self-healable o-alg-THAM/gel hydrogel system as scaffolds and a biophysio-enhanced bioactive microspheres engineered based on hBMSCs secretion during chondrogenic differentiation as bioactive supplement,the as proposed functional material effectively and specifically recruit endogenous stem cells for cartilage repair,providing new insights into in situ articular cartilage regeneration.

关键词： Bioactive hydrogels Solidified secretome Adhesive hydrogels Acellular functional scaffold cartilage repair

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Recent advances in polymeric biomaterials-based gene delivery for cartilage repair

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Bioactive Materials 2020年第4期5卷 990-1003页

作者： Ran Yang Fei Chen Jinshan Guo Dongfang Zhou Shifang Luan State Key Laboratory of Polymer Physics and Chemistry Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun130022PR China School of Pharmaceutical Sciences Southern Medical UniversityGuangzhou510515PR China College of Applied Chemistry and Engineering University of Science and Technology of ChinaHefei230026PR China Center for Materials Synthetic Biology CAS Key Laboratory of Quantitative Engineering BiologyShenzhen Institute of Synthetic BiologyShenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhen518055PR China Department of Histology and Embryology School of Basic Medical SciencesSouthern Medical UniversityGuangzhou510515PR China

Untreated articular cartilage damage normally results in osteoarthritis and even disability that affects millions of ***,both the existing surgical treatment and tissue engineering approaches are unable to regenerate the original structures of articular cartilage durably,and new strategies for integrative cartilage repair are *** therapy provides local production of therapeutic factors,especially guided by biomaterials can minimize the diffusion and loss of the genes or gene complexes,achieve accurate spatiotemporally release of gene products,thus provideing long-term treatment for cartilage *** widespread application of gene therapy requires the development of safe and effective gene delivery vectors and supportive gene-activated *** them,polymeric biomaterials are particularly attractive due to their tunable physiochemical properties,as well as excellent adaptive *** paper reviews the recent advances in polymeric biomaterial-guided gene delivery for cartilage repair,with an emphasis on the important role of polymeric biomaterials in delivery systems.

关键词： cartilage repair Gene therapy Polymeric biomaterials Delivery vectors Gene-activated matrices

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Recent strategies of collagen-based biomaterials for cartilage repair: from structure cognition to function endowment

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Journal of Leather Science and Engineering 2022年第1期4卷 152-174页

作者： Xiaoyue Yu Haiping Zhang Yiliang Miao Shanbai Xiong Yang Hu College of Food Science and Technology Huazhong Agricultural UniversityWuhan 430070HubeiPeople’s Republic of China Shenzhen Institute of Nutrition and Health Huazhong Agricultural UniversityWuhan 430070HubeiPeople’s Republic of China Bioactive Peptide Technology Hubei Engineering Research Center No.195 Dongfang AveJingzhou 434000HubeiPeople’s Republic of China.

Collagen,characteristic in biomimetic composition and hierarchical structure,boasts a huge potential in repairing cartilage defect due to its extraordinary bioactivities and regulated physicochemical properties,such as low immunogenicity,biocompatibility and controllable degradation,which promotes the cell adhesion,migration and ***,collagen-based biomaterial has been explored as porous scaffolds or functional coatings in cell-free scaffold and tissue engineering strategy for cartilage *** those forming technologies,freeze-dry is frequently used with special modifications while 3D-printing and electrospinning serve as the structure-controller in a more precise ***,appropriate cross-linking treatment and incorporation with bioactive substance generally help the collagen-based biomaterials to meet the physicochemical requirement in the defect site and strengthen the repairing ***,comprehensive evaluations on the repair effects of biomaterials are sorted out in terms of in vitro,in vivo and clinical assessments,focusing on the morphology observation,characteristic production and critical gene ***,the challenge of biomaterial-based therapy for cartilage defect repairing was summarized,which is,the adaption to the highly complex structure and functional difference of cartilage.

关键词： Collagen cartilage repair Hierarchical structure Structure cognition Function endowment

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Morphological MRI and T2 mapping of cartilage repair tissue after mosaicplasty with tissue-engineered cartilage in a pig model

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The Journal of Biomedical Research 2014年第4期28卷 309-319页

作者： Qichun Chen Qiang Zuo Qianqian Hu Yang Feng Weiding Cui Weimin Fan Yuefen Zou Department of Radiology the Second Hospital of Anhui Medical University Department of Orthopedics the First Affiliated Hospital of Nanjing Medical University Department of Radiology the First Affiliated Hospital of Nanjing Medical University

The aim of this study was to evaluate the efficacy of mosaicplasty with tissue-engineered cartilage for the treatment of osteochondral defects in a pig model with advanced MR technique. Eight adolescent miniature pigs were used. The right knee underwent mosaicplasty with tissue-engineered cartilage for treatment of focal osteochondral defects, while the left knee was repaired via single mosaicplasty as controls. At 6, 12, 18 and 26 weeks after surgery, repair tissue was evaluated by magnetic resonance imaging （MRI） with the cartilage repair tissue （MOCART） scoring system and T2 mapping. Then, the results of MRI for 26 weeks were compared with findings of macroscopic and histologic studies. The MOCART scores showed that the repaired tissue of the tissue-engineered cartilage group was statistically better than that of controls （P 〈 0.001）. A significant correlation was found between macroscopic and MOCART scores （P 〈 0.001）. Comparable mean T2 values were found between adjacent cartilage and repair tissue in the experimental group （P 〉 0.05）. For zonal T2 value evaluation, there were no significant zonal T2 differences for repair tissue in controls （P 〉 0.05）. For the experimental group, zonal T2 variation was found in repair tissue （P 〈 0.05）. MRI, macroscopy and histology showed better repair results and bony incorporation in mosaicplasty with the tissue-engi- neered cartilage group than those of the single mosaicplasty group. Mosaicplasty with the tissue-engineered cartilage is a promising approach to repair osteochodndral defects. Morphological MRI and T2 mapping provide a non-invasive method for monitoring the maturation and integration of cartilage repair tissue in vivo.

关键词： cartilage repair mosaicplasty tissue engineering magnetic resonance imaging T2 mapping

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Preparation of EGCG decorated,injectable extracellular vesicles for cartilage repair in rat arthritis

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Regenerative Biomaterials 2021年第6期8卷 209-217页

作者： Changwei Song Shibo Xu Linna Chang Xingjun Zhao Xifan Mei Xiuli Ren Zhenhua Chen First Affiliated Hospital of Jinzhou Medical University Jinzhou 121001China Jinzhou Medical University JinzhouLiaoning 121001China

Arthritis is a kind of chronic inflammatory autoimmune disease,which can destroy joint cartilage and bone,leading to joint pain,joint swelling,and limited *** therapies have many side effects or focus too much on anti-inflammation while neglecting joint *** this experiment,we combined Epigallocatechin gallate(EGCG)with extracellular vesicles derived from macrophages to treat rheumatoid ***-release resulted in a significant decrease in chondrocyte expression of hypoxia-inducible factor 1-alpha,a decrease in apoptosis-related proteins Cytochrome C,Caspase-3,Caspase-9,and *** biological analysis showed that extracellular vesicles-encapsulated EGCG(EVs-EGCG)more significantly upregulated type II collagen expression by about 1.8-fold than EGCG alone,which was more beneficial for arthritis *** experiments revealed that these EGCG-coated extracellular vesicles significantly reduced swelling,decreased synovial hyperplasia,repaired cartilage,and attenuated arthritis-related pathology scores in arthritic *** data showed that EVs-EGCG treatment reduced joint swelling by approximately 39.5%in rheumatoid *** vitro studies have shown that this EVs-EGCG can increase the expression of cartilage type II collagen and reduce apoptosis of ***,it was demonstrated in vivo experiments to reduce cartilage destruction in rheumatoid arthritis rats,providing a solution for the treatment of rheumatoid arthritis.

关键词： cartilage repair arthritis tea polyphenol extracellular vesicles

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Effect of low-energy shock waves in microfracture holes in the repair of articular cartilage defects in a rabbit model

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Chinese Medical Journal 2011年第9期124卷 1386-1394页

作者： WANG Qi LI Zhong-li FU Yang-mu WANG Zhi-gang WEI Min ZHAO Bin ZHANG Li ZHU Juan-li Department of Orthopedics Sports Medicine Center People's Liberation Army General Hospital Beijing 100853 China

Background Microfracture is a type of bone marrow stimulation in arthroscopic cartilage repair. However, the overall concentration of the mesenchymal stem cells is quite low and declines with age, and in the end the lesion is filled by fibrocartilage. The aim of this research was to investigate a novel method of enhancing microfracture by determining whether low-energy shock waves in microfracture holes would facilitate cartilage repair in a rabbit *** Full-thickness cartilage defects were created at the medial femoral condyle of 36 mature New Zealand white rabbits without penetrating subchondral bone. The rabbits were randomly divided into three groups. In experimental group A, low-energy shock-wave therapy was performed in microfracture holes （diameter, 1 mm） at an energy flux density （EFD） of 0.095 m J/mm2 and 200 impulses by DolorClast Master （Electro Medical Systems SA, Switzerland）microprobe （diameter, 0.8 mm）. In experimental group B, microfracture was performed alone. The untreated rabbits served as a control group. At 4, 8, and 12 weeks after the operations, repair tissues at the defects were analyzed stereologically, histologically, and *** The defects were filled gradually with repair tissues in experimental groups A and B, and no repair tissues had formed in the control group at 12 weeks. repair tissues in experimental group A contained more chondrocytes,proteoglycans, and collagen type Ⅱ than those in experimental group B. In experimental group B, fibrous tissues had formed at the defects at 8 and 12 weeks. Histological analysis of experimental group A showed a better Wakitani score （P ＜0.05） than in experimental group B at 8 and 12 weeks after the *** In the repair of full-thickness articular cartilage defects in rabbits, low-energy shock waves in microfracture holes facilitated the production of hyaline-like cartilage repair tissues more than microfracture alone. This model demonstrates a new metho

关键词： articular cartilage repair marrow stimulation shock waves

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A versatile 3D-printable hydrogel for antichondrosarcoma,antibacterial,and tissue repair

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Journal of Materials Science & Technology 2023年第5期136卷 200-211页

作者： Wenxiang Zhu Zheng Zhou Yuting Huang Hairong Liu Ning He Xiaolong Zhu Xiaoxiao Han Dengming Zhou Xuanchu Duan Xin Chen Yahui He Xiaolin Meng Shuai Zhu College of Materials Science and Engineering Hunan UniversityChangsha 410082China College of Biology Hunan UniversityChangsha 410082China State Key Laboratory of Advanced Design and Manufacture for Vehicle Body Hunan UniversityChangsha 410082China Department of Ophthalmology The Second Xiangya HospitalCentral South UniversityChangsha 410011China Aier Glaucoma Institute Changsha 410000China Aier School of Ophthalmology Central South UniversityChangsha 410000China Changsha Aier Eye Hospital Aier Eye Hospital GroupChangsha 410000China

Following operative treatment of chondrosarcoma,post-surgery tissue reconstruction may be confronted with daunting challenges,including the delayed self-repair of defective tissue,tumor recurrence,and bac-terial *** overcome these challenges,a methacrylic anhydride(MA)modified sericin(SerMA)solution mixed with procyanidins(PC)loaded polydopamine(PDA)modified ZIF-8(PC@ZIF-8@PDA)nanoparticles to form a multifunctional PC@ZIF-8@PDA/SerMA hydrogel after exposure under blue *** products with pre-designed shapes were printed out by using the SerMA solution carrying PC@ZIF-8@PDA nanoparticles and chondrocytes,indicating that PC@ZIF-8@PDA/SerMA hydrogels with personalized shapes can be fabricated via 3D *** PC@ZIF-8@PDA/SerMA hydrogel is able to kill chondrosarcoma cells and bacteria,like Staphylococcus aureus(***),and Escherichia coli(***),by its photothermal activity combined with near-infrared radiation(NIR).The PC@ZIF-8@PDA/SerMA hydrogel exhibited an antioxidative activity and a good biocompatibility and was easily monitored by its florescent and photoacoustic *** articular cartilage defects were efficiently repaired by PC@ZIF-8@PDA/SerMA hydrogels with encapsulated corresponding autologous chondrocytes,and mice skin burning wounds were swiftly regenerated by applying this ***,the PC@ZIF-8@PDA/SerMA hydrogel can be potentially applied to the clinic treatment of chondrosarcoma and tissue defect repair after chondrosarcoma resection due to its multifunction in the future.

关键词： Hydrogel Sericin ZIF-8 Chondrosarcoma cartilage repair

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