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MSCs-laden Injectable self-healing hydrogel for systemic sclerosis treatment

Bioactive Materials 2022年第11期7卷 369-378页

作者： Min Nie Bin Kong Guopu Chen Ying Xie Yuanjin Zhao Lingyun Sun Department of Rheumatology and Immunology Institute of Translational MedicineThe Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing210002China Department of Neurosurgery Health Science CenterThe First Affiliated Hospital of Shenzhen UniversityShenzhen Second People’s HospitalShenzhen518035China State Key Laboratory of Quality Research in Chinese Medicines Macao University of Science and TechnologyTaipaMacao(SAR)China State Key Laboratory of Bioelectronics School of Biological Science and Medical EngineeringSoutheast UniversityNanjing210096China

As a novel cellular therapy, the anti-inflammatory and immunomodulatory virtues of mesenchymal stem cells (MSCs) make them promising candidates for systemic sclerosis (SSc) treatment. However, the clinical efficacy of this stratagem is limited because of the short persistence time, poor survival, and engraftment of MSCs after injection in vivo. Herein, we develop a novel MSCs-laden Injectable self-healing hydrogel for SSc treatment. The hydrogel is prepared using N, O-carboxymethyl chitosan (CS-CM) and 4-armed benzaldehyde-terminated poly-ethylene glycol (PEG-BA) as the main components, imparting with self-healing capacity via the reversible Schiff-base connection between the amino and benzaldehyde groups. We demonstrate that the hydrogel laden with MSCs not only promoted the proliferation of MSCs and increased the cellular half-life in vivo, but also improve their immune-modulating functions. The tube formation assay indicates that the MSCs could significantly pro-mote angiopoiesis. Moreover, the MSCs-laden hydrogel could inhibit fibrosis by modulating the synthesis of collagen and ameliorate disease progression in SSc disease model mice after subcutaneous injection of bleo-mycin. All these results highlight this novel MSCs-laden hydrogel and its distinctive functions in treatment of chronic SSc, indicating the additional potential to be used widely in the clinic.

关键词： Mesenchymal Stem cell Injectable Self-healing Hydrogel Systemic sclerosis

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Design and fabrication of high-performance Injectable self-setting trimagnesium phosphate

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Bioactive Materials 2023年第10期28卷 348-357页

作者： Jiawei Liu Wen Hou Wenying Wei Jian Peng Xiaopei Wu Chenxi Lian Yanan Zhao Rong Tu Takashi Goto Honglian Dai State Key Laboratory of Advanced Technology for Materials Synthesis and Processing Biomedical Materials and Engineering Research Center of Hubei ProvinceWuhan University of TechnologyWuhan 430070China Chaozhou Branch of Chemistry and Chemical Engineering Guangdong Laboratory Chaozhou 521000China New Industry Creation Hatchery Center Tohoku UniversitySendai 980-8579Japan

Magnesium phosphate bone cement has become a widely used orthopedic implant due to the advantages of fast-setting and high early strength. However, developing magnesium phosphate cement possessing applicable injectability, high strength, and biocompatibility simultaneously remains a significant challenge. Herein, we propose a strategy to develop high-performance bone cement and establish a trimagnesium phosphate cement (TMPC) system. The TMPC exhibits high early strength, low curing temperature, neutral pH, and excellent injectability, overcoming the critical limitations of recently studied magnesium phosphate cement. By monitoring the hydration pH value and electroconductivity, we demonstrate that the magnesium-to-phosphate ratio could manipulate the components of hydration products and their transformation by adjusting the pH of the system, which will influence the hydration speed. Further, the ratio could regulate the hydration network and the properties of TMPC. Moreover, in vitro studies show that TMPC has outstanding biocompatibility and bone-filling capacity. The facile preparation properties and these advantages of TMPC render it a potential clinical alternative to polymethylmethacrylate and calcium phosphate bone cement. This study will contribute to the rational design of high-performance bone cement.

关键词： Bone cement Trimagnesium phosphate High compressive strength Injectable Bioactive materials

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Effect of surgical factors on the augmentation of cementInjectable cannulated pedicle screw fixation by a novel calcium phosphate-based nanocomposite

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Frontiers of Medicine 2019年第5期13卷 590-601页

作者： Haolin Sun Chun Liu Shunlun Chen Yanjie Bai Huilin Yang Chunde Li Lei Yang Department of Orthopedics Peking University First Hospital Beijing 100034China Orthopedic Institute Department of OrthopedicsFirst Affiliated HospitalSoochow UniversitySuzhou 215006China School of Public Health Medical CollegeSoochow UniversitySuzhou 215100China International Research Center for Translational Orthopedics Suzhou 215006China School of Materials Science and Engineering Hebei University of TechnologyTianjin 300130China

Bone cement-augmented pedicle screw system demonstrates great efficacy in spinal disease treatments. However, the intrinsic drawbacks associated with clinically used polymethylmethacrylate (PMMA) cement demands for new bone cement formulations. On the basis of our previous studies, a novel Injectable and biodegradable calcium phosphate-based nanocomposite (CPN) for the augmentation of pedicle screw fixation was systematically evaluated for its surgical feasibility and biomechanical performance by simulated and animal osteoporotic bone models, and the results were compared with those of clinical PMMA cement. ASTM-standard solid foam and open-cell foam models and decalcified sheep vertebra models were employed to evaluate the augmentation effects of CPN on bone tissue and on the cement-injected cannulated pedicle screws (CICPs) placed in osteoporotic bone. Surgical factors in CICPs application, such as injection force, tapping technique, screw diameter, and pedicle screw loosening scenarios, were studied in comparison with those in PMMA. When directly injected to the solid foam model, CPN revealed an identical augmentation effect to that of PMMA, as shown by the similar compressive strengths (0.73 ± 0.04 MPa for CPN group vs. 0.79 ± 0.02 MPa for PMMA group). The average injection force of CPN at approximately 40-50 N was higher than that of PMMA at approximately 20 N. Although both values are acceptable to surgeons, CPN revealed a more consistent injection force pattern than did PMMA. The dispersing and anti-pullout ability of CPN were not affected by the surgical factors of tapping technique and screw diameter. The axial pullout strength of CPN evaluated by the decalcified sheep vertebra model revealed a similar augmentation level as that of PMMA (1351.6 ± 324.2 N for CPN vs. 1459.7 ± 304.4 N for PMMA). The promising results of CPN clearly suggest its potential for replacing PMMA in CICPs augmentation application and the benefits of further study and development for clinical uses.

关键词： bone cement pedicle screw degenerative spinal diseases calcium phosphate Injectable

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用于骨缺损修复的新型可注射自固化复合材料

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Science China Materials 2020年第5期63卷 876-887页

作者：徐倩梁久龙薛海鹏柳云恩曹磊李小武田竞张兴 Department of Materials Physics and Chemistry School of Materials Science and EngineeringKey Laboratory for Anisotropy and Texture of MaterialsMinistry of EducationNortheastern UniversityShenyang 110819China Institute of Metal Research Chinese Academy of SciencesShenyang 110016China General Hospital of Northern Theater Command Shenyang 110016China School of Materials Science and Engineering University of Science and Technology of ChinaHefei 230026China

硫酸钙骨水泥具有良好的骨传导性,但降解速率快、生物活性差的缺点限制了其临床应用.本文将β-磷酸三钙纳米颗粒(粒径43.8±9.0 nm)和半水硫酸钙颗粒(粒径5–21μm)混合作为固相,与液相聚乙烯醇溶液(5 wt.%)按优化重量比混匀,制备了可... 详细信息

硫酸钙骨水泥具有良好的骨传导性,但降解速率快、生物活性差的缺点限制了其临床应用.本文将β-磷酸三钙纳米颗粒(粒径43.8±9.0 nm)和半水硫酸钙颗粒(粒径5–21μm)混合作为固相,与液相聚乙烯醇溶液(5 wt.%)按优化重量比混匀,制备了可注射自固化复合材料.该材料具有合理的自固化时间(11.7–19.2 min)及适宜的压缩强度(2.28–6.33 MPa).同时,利用镁颗粒作为成孔剂,制备出大孔径(大于100μm)的多孔支架.体外细胞实验显示,MC3T3-E1细胞伸展良好,表现出大量的板状伪足和伸展的丝状伪足,表明该复合材料无细胞毒性.将可注射复合材料植入比格犬股骨髁缺损区,10个月后骨缺损愈合良好,表明该材料具有良好的骨缺损修复潜力.

关键词： nanoparticles magnesium substitution Injectable materials self-setting bone defect repair

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Injectable hydrogel wound dressing based on strontium ion cross-linked starch

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Frontiers of Materials Science 2020年第2期14卷 232-241页

作者： Yuxuan MAO Mingming PAN Huilin YANG Xiao LIN Lei YANG College of Chemistry Chemical Engineering and Materials ScienceOrthopaedic InstituteSoochow UniversitySuzhou 215006China Department of Orthopaedics The First ffiliated HospitalSoochow UniversitySuzhou 215006China Center for Health Science and Engineering School of Materials Science and EngineeringHebei University of TechnologyTianjin 300131China

Severe skin wounds cause great problems and sufferings to patients.In this study,an Injectable wound dressing based on strontium ion cross-linked starch hydrogel(SSH)was developed and evaluated.The good inject-ability of SSH made it easy to be delivered onto the wound surface.The good tissue adhesiveness of SSH ensured a firm protection of the wound.Besides,SSH supported the proliferation of NIH/3T3 fibroblasts and facilitated the migration of human umbilical vein endothelial cells(HUVECs).Importantly,SSH exhibited strong antibacterial effects on Staphylococcus aiireiis(S.ai/rec/s),which could prevent wound infection.These results demonstrate that SSH is a promising wound dressing material for promoting wound healing.

关键词： wound dressing Injectable antibacterial gel-point adhesive hydrogel(GPAH)

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Injectable baicalin/F127 hydrogel with antioxidant activity for enhanced wound healing

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Chinese Chemical Letters 2020年第7期31卷 1817-1821页

作者： Guiting Liu Ziting Bao Jun Wu Key Laboratory of Sensing Technology and Biomedical Instrument of Guangdong Province School of Biomedical Engineering.Sun Yat-sen UniversityGuangzhou 510006China Research Institute of Sun Yat-sen University in Shenzhen Shenzhen 518057China

Baicalin,extracted from traditional Chinese medicine Scutellaria baicalensis Georg,possesses multiple pharmacological activities and has great potential for chronic skin wound repair.However,the poor solubility and lack of suitable vehicles greatly limit its further application.Herein,we proposed a convenient and robust strategy,employing PBS solution as solvent,to enhance the solubility of baicalin.Furthermore,we constructed Injectable baicalin/F127 hydrogels to study their application in skin wound treatment.The composition and temperature sensitivity of baicalin/Pluronic®F-127 hydrogels were confirmed by FTIR and rheological testing,respectively.In vitro release measurement indicated that the first order model was best fitted with the release profile of baicalin from hydrogel matrix.Besides,MTT assay,AO/EO staining assay as well as hemolytic activity test revealed the excellent cytocompatibility of baicalin/F127 hydrogels.Antioxidant activity assay demonstrated the cytoprotective activity of baicalin/F127 hydrogels against reactive oxygen species(ROS).Furthermore,the in vivo experiments exhibited the ability of baicalin/F127 hydrogel to accelerate wound healing.In conclusion,this novel Injectable baicalin/F127 hydrogel should have bright application for chronic wound treatment.

关键词： Wound healing Hydrogel Baicalin Antioxidant Injectable

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A polysaccharide/tetraphenylethylene-mediated blue-light emissive and Injectable supramolecular hydrogel

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Chinese Chemical Letters 2018年第1期29卷 84-86页

作者： Qian Zhao Yong Chen Yu Liu College of Chemistry State Key Laboratory of Elemento-Organie Chemistry Nankai University tianjin 300071 China Collaborative Innovation Center of Chemical Science and Engineering (tianjin) Nankai University Tianjin 300071 China

A luminescent and Injectable supramolecular hydrogel was successfully constructed through the non- covalent cross-linking of polymers mediated by tetraphenylethylene-bridged cyclodextrin oligomers, presenting the strong blue fluorescence, the reversible gelation behavior responsive to various external stimuli and the good mechanical property of shear thinning.

关键词： Tetraphenylethylene Supramolecular Emissive Injectable Hydrogel

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Preparation and evaluation of a phospholipid-based Injectable gel for the long term delivery of leuprolide acetaterrh

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Acta Pharmaceutica Sinica B 2016年第4期6卷 329-335页

作者： Danhong Long Tao Gong Zhirong Zhang Rui Ding Yao Fu Key Laboratory of Drug Targeting and Drug Delivery Systems Ministry of Education West China School of PharmacySichuan University Beijing Institute for Drug Control

A phospholipid-based Injectable gel was developed for the sustained delivery of leuprolide acetate(LA). The gel system was prepared using biocompatible materials(SPME), including soya phosphatidyl choline(SPC), medium chain triglyceride(MCT) and ethanol. The system displayed a sol state with low viscosity in vitro and underwent in situ gelation in vivo after subcutaneous injection. An in vitro release study was performed using a dialysis setup with different release media containing different percentages of ethanol. The stability of LA in the SPME system was investigated under different temperatures and in the presence of various antioxidants. In vivo studies in male rats were performed to elucidate the pharmacokinetic profiles and pharmacodynamic efficacy. A sustained release of LA for 28 days was observed without obvious initial burst in vivo. The pharmacodynamic study showed that once-amonth injection of LA-loaded SPME(SPME-LA) led to comparable suppression effects on the serum testosterone level as observed in LA solution except for the onset time. These findings demonstrate excellent potential for this novel SPME system as a sustained release delivery system for LA.

关键词： Phospholipids Injectable gel Leuprolide acetate Pharmacokinetics Testosterone

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Promotion of Neurite Outgrowth and Extension Using Injectable Welded Nanofibers

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Chemical Research in Chinese Universities 2021年第3期37卷 522-527页

作者： FENG Zhendong ZHANG Xiaopei LIU Na WANG Yue ZHOU Ziyi GLEBOV O.Oleg WU Tong Institute of Neuroregeneration and Neurorehabilitation Qingdao UniversityQingdao266071P.R.China Qingdao Medical College Qingdao UniversityQingdao266071P.R.China Department of Old Age Psychiatry The Institute of PsychiatryPsychology&NeuroscienceKing’s College LondonDe Crespigny ParkDenmark HillLondonSE58AFUK

We report a general strategy to develop Injectable welded nanofibers to facilitate the outgrowth and extension of neurites.In this case,nonwoven mats of uniaxially aligned poly(caprolactone)(PCL)nanofibers were firstly cut into several small pieces with fixed fiber lengths of 25,50 and 100µm,respectively,using a cryotome.A tissuelyser was employed to homogenize and disperse the short nanofibers to a homogeneous suspension.By tuning treatment duration from 100 s to 400 s,the temperature of the suspension was brought close to the melting point of PCL.As such,the short nanofibers were welded at their cross points while the fibers far away from the cross points remain the original structures.We showed that the viability of neuroblastoma SH-SY5Y cells and their neurite outgrowth and extension were enhanced with the use of such welded short nanofibers.Taken together,this study provides a simple way to generate Injectable welded nanofibers,holding potential in affecting neurite outgrowth and extension for nerve repair,in particular,in the central nervous system.

关键词： Electrospinning Nanofiber Welding Injectable Neurite outgrowth

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In vivo bone regeneration with Injectable chitosan/hydroxyapatite/collagen composites and mesenchymal stem cells

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Frontiers of Computer Science 2011年第3期5卷 301-310页

作者： Zhi HUANG Yan CHEN Qing-Ling FENG Wei ZHAO Bo YU Jing TIAN Song-Jian LI Bo-Miao LIN Department of Materials Science and Engineering Tsinghua University Beijing 100084 China Department of Ultrasonic Diagnosis Zhujiang Hospital of Southern Medical University Guangzhou 510282 China Institute of High Energy Physics Chinese Academy of Sciences Beijing 100049 China Department of Orthopedics Zhujiang Hospital of Southern Medical University Guangzhou 510282 China Department of Radiology Zhujiang Hospital of Southern Medical University Guangzhou 510282 China

For reconstruction of irregular bone defects, Injectable biomaterials are more appropriate than the preformed biomaterials. We herein develop a biomimetic in situ-forming composite consisting of chitosan （CS） and mineralized collagen fibrils （nHAC）, which has a complex hierarchical structure similar to natural bone. The CSInHAC composites with or without mesenchymal stem cells （MSCs） are injected into cancellous bone defects at the distal end of rabbit femurs. Defects are assessed by radiographic, histological diagnosis and Raman microscopy until 12 weeks. The results show that MSCs improve the biocompatibility of CS/nHAC composites and enhance new bone formation in vivo at 12 weeks. It can be concluded that the Injectable CSInHAC composites combined with MSCs may be a novel method for reconstruction of irregular bone defects.

关键词： mineralized collagen fibrils in situ-forming Injectable mesenchymal stem cells tissue engineered bone

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