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Capturing dynamic biological signals via bio-mimicking hydrogel for precise remodeling of soft tissue

Bioactive Materials 2021年第12期6卷 4506-4516页

作者： Zhengwei Cai Qimanguli Saiding Liang Cheng Liucheng Zhang Zhen Wang Fei Wang Xinliang Chen Gang Chen lianfu deng Wenguo Cui 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 Jiaxing Key Laboratory of Basic Research and Clinical Translation on Orthopedic Biomaterials Department of OrthopaedicsThe Second Affiliated Hospital of Jiaxing University1518 North Huancheng RoadJiaxing314000China Shanghai Key Laboratory of Embryo Original Diseases The International Peace Maternal and Child Health HospitalSchool of MedicineShanghai Jiao Tong University910 Hengshan RoadShanghai200030PR China

Soft tissue remodeling is a sophisticated process that sequentially provides dynamic biological signals to guide cell ***,capturing these signals within hydrogel and directing over time has still been unrealized owing to the poor comprehension of physiological ***,a bio-mimicking hydrogel is designed via thiol-ene click reaction to capture the early physical signal triggered by inflammation,and the chemical signals provided with chemokine and natural adhesion sites,which guaranteed the precise soft tissue *** bio-mimicking hydrogel efficiently facilitated cell anchoring,migration,and invasion in the 3D matrix due to the permissive space and the interaction with integrin ***,the covalently grafted chemokine-like peptide is optimal for colonization and functional differentiation of endothelial cells through a HIF-1αdependent signal ***,the early polarization of macrophages,collagen deposition and angiogenesis in rat acute wound model,and the increased blood perfusion in mouse skin flap model have confirmed that the bio-mimicking hydrogel realized precise soft tissue remodeling and opens new avenues for the phased repair of different tissues such as nerve,myocardium,and even bone.

关键词： Biological signals Physiological phase Hydrogel Chemotactic Soft tissue remodeling

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Lotus seedpod-inspired internal vascularized 3D printed scaffold for bone tissue repair

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Bioactive Materials 2021年第6期6卷 1639-1652页

作者： Xiaoyu Han Mingjie Sun Bo Chen Qimanguli Saiding Junyue Zhang Hongliang Song lianfu deng Peng Wang Weiming Gong Wenguo Cui Department of Orthopedics Jinan Central HospitalShandong First Medical University&Shandong Academy of Medical Sciences105 Jiefang RoadLixia DistrictJinanShandong250013PR China Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases Shanghai Institute of Traumatology and OrthopedicsRuijin HospitalShanghai Jiao Tong University School of Medicine197 Ruijin 2nd RoadShanghai200025PR China

In the field of bone defect repair,3D printed scaffolds have the characteristics of personalized customization and accurate internal ***,how to construct a well-structured vascular network quickly and effectively inside the scaffold is essential for bone repair after ***,inspired by the unique biological structure of“lotus seedpod”,hydrogel microspheres encapsulating deferoxamine(DFO)liposomes were prepared through microfluidic technology as“lotus seeds”,and skillfully combined with a three-dimensional(3D)printed bioceramic scaffold with biomimetic“lotus”biological structure which can internally grow blood *** this composite scaffold system,DFO was effectively released by 36%in the first 6 h,which was conducive to promote the growth of blood vessels inside the scaffold *** the following 7 days,the release rate of DFO reached 69%,which was fundamental in the formation of blood vessels inside the scaffold as well as osteogenic differentiation of bone mesenchymal stem cells(BMSCs).It was confirmed that the composite scaffold could significantly promote the human umbilical vein endothelial cells(HUVECs)to form the vascular morphology within 6 h in *** vivo,the composite scaffold increased the expression of vascularization and osteogenic related proteins Hif1-α,CD31,OPN,and OCN in the rat femoral defect model,significantly cutting down the time of bone *** sum up,this“lotus seedpod”inspired porous bioceramic 3D printed scaffold with internal vascularization functionality has broad application prospects in the future.

关键词： 3D scaffolds Drug release Neovascularization Osteogenesis Regeneration

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Biomimetic injectable hydrogel microspheres with enhanced lubrication and controllable drug release for the treatment of osteoarthritis

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Bioactive Materials 2021年第10期6卷 3596-3607页

作者： Ying Han Jielai Yang Weiwei Zhao Haimang Wang Yulong Sun Yuji Chen Jing Luo lianfu deng Xiangyang Xu Wenguo Cui Hongyu Zhang State Key Laboratory of Tribology Department of Mechanical EngineeringTsinghua UniversityBeijing100084China 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 MedicineShanghai200025China Beijing Research Institute of Automation for Machinery Industry Co. LtdBeijing100120China

The occurrence of osteoarthritis(OA)is highly associated with the reduced lubrication property of the joint,where a progressive and irreversible damage of the articular cartilage and consecutive inflammatory response dominate the *** this study,bioinspired by the super-lubrication property of cartilage and catecholamine chemistry of mussel,we successfully developed injectable hydrogel microspheres with enhanced lubrication and controllable drug release for OA ***,the lubricating microspheres(GelMA@DMA-MPC)were fabricated by dip coating a self-adhesive polymer(DMA-MPC,synthesized by free radical copolymerization)on superficial surface of photo-crosslinked methacrylate gelatin hydrogel microspheres(GelMA,prepared via microfluidic technology),and encapsulated with an anti-inflammatory drug of diclofenac sodium(DS)to achieve the dual-functional *** tribological test and drug release test showed the enhanced lubrication and sustained drug release of the GelMA@DMA-MPC *** addition,the functionalized microspheres were intra-articularly injected into the rat knee joint with an OA model,and the biological tests including qRT-PCR,immunofluorescence staining assay,X-ray radiography and histological staining assay all revealed that the biocompatible microspheres provided significant therapeutic effect against the development of *** summary,the injectable hydrogel microspheres developed herein greatly improved lubrication and achieved sustained local drug release,therefore representing a facile and promising technique for the treatment of OA.

关键词： Microfluidics Hydrogel microspheres Catecholamine chemistry Hydration lubrication Drug delivery

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Click chemistry extracellular vesicle/peptide/chemokine nanocarriers for treating central nervous system injuries

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Acta Pharmaceutica Sinica B 2023年第5期13卷 2202-2218页

作者： Huitong Ruan Yongfang Li Cheng Wang Yixu Jiang Yulong Han Yiwei Li Dandan Zheng Jing Ye Gang Chen Guo-yuan Yang lianfu deng Ming Guo Xingcai Zhang Yaohui Tang Wenguo Cui 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 MedicineShanghai 200025China Jiaxing Key Laboratory of Basic Research and Clinical Translation on Orthopedic Biomaterials Department of Orthopaedicsthe Second Affiliated Hospital of Jiaxing UniversityJiaxing 314000China Department of Rehabilitation Medicine Ruijin HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200025China Med-X Research Institute and School of Biomedical Engineering Shanghai Jiao Tong UniversityShanghai 200030China School of Engineering Massachusetts Institute of TechnologyCambridgeMA 02139USA School of Engineering and Applied Sciences Harvard UniversityCambridgeMA 02138USA

Central nervous system(CNS)injuries,including stroke,traumatic brain injury,and spinal cord injury,are essential causes of death and long-term disability and are difficult to cure,mainly due to the limited neuron regeneration and the glial scar ***,we apply extracellular vesicles(EVs)secreted by M2 microglia to improve the differentiation of neural stem cells(NSCs)at the injured site,and simultaneously modify them with the injured vascular targeting peptide(DA7R)and the stem cell recruiting factor(SDF-1)on their surface via copper-free click chemistry to recruit NSCs,inducing their neuronal differentiation,and serving as the nanocarriers at the injured site(Dual-EV).Results prove that the Dual-EV could target human umbilical vascular endothelial cells(HUVECs),recruit NSCs,and promote the neuronal differentiation of NSCs in ***,10 miRNAs are found to be upregulated in Dual-M2-EVs compared to Dual-M0-EVs via bioinformatic analysis,and further NSC differentiation experiment by flow cytometry reveals that among these miRNAs,miR30b-3p,miR-222-3p,miR-129-5p,and miR-155-5p may exert effect of inducing NSC to differentiate into *** vivo experiments show that Dual-EV nanocarriers achieve improved accumulation in the ischemic area of stroke model mice,potentiate NSCs recruitment,and increase *** work provides new insights for the treatment of neuronal regeneration after CNS injuries as well as endogenous stem cells,and the click chemistry EV/peptide/chemokine and related nanocarriers for improving human health.

关键词： Central nervous system injuries Stroke Neural stem cell Neurogenesis Click chemistry Extracellular vesicles Microglia Targeted delivery

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骨修复材料的研究现状与进展

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中国修复重建外科杂志 2018年第7期32卷 815-820页

作者：邓廉夫燕宇飞上海交通大学医学院附属瑞金医院上海市伤骨科研究所上海200025

人工骨修复材料是自体骨移植最佳替代品,骨修复材料的发展大致可以分为3代:惰性材料、生物活性材料、智能型材料。研发具备多种生物学活性、体内降解与新骨生成完美适配、能完全重建生理状态下骨组织的骨修复材料是未来研究重点。

关键词：骨修复生物材料研究进展

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发育性髋关节发育不良的发生与防治研究进展

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中华骨科杂志 2022年第1期42卷 54-64页

作者：季策李长伟邓廉夫上海交通大学医学院附属瑞金医院骨科上海市伤骨科研究所上海市中西医结合防治骨与关节病损重点实验室200025

发育性髋关节发育不良(developmental dysplasia of the hip,DDH)是小儿骨科最常见的疾病之一。DDH发病因素复杂,对其发生与发展的分子调控机制目前尚不清楚。了解髋关节发育过程的分子调节机制与形态学变化,对DDH发病机制的探究、早期... 详细信息

发育性髋关节发育不良(developmental dysplasia of the hip,DDH)是小儿骨科最常见的疾病之一。DDH发病因素复杂,对其发生与发展的分子调控机制目前尚不清楚。了解髋关节发育过程的分子调节机制与形态学变化,对DDH发病机制的探究、早期筛查与诊疗策略的制订具有重要意义。近年来,随着发育生物学、分子生物学、基础医学以及临床医学的发展,对DDH发生、发展的风险因素以及潜在的致病机制有了更新的认知。本文综述了目前在髋关节进化过程、人类髋关节发育过程中解剖结构的变化、参与骨发育中软骨内成骨的基因及信号通路等方面的研究进展;分析了可能发生发育不稳定的时间节点,并对DDH发病的危险因素、临床筛查以及诊疗现状进行了总结。胚胎发育过程中股骨头和髋臼的相互作用决定了髋关节的形态发生,在怀孕5~12周开始出现髋关节软骨雏形,之后经历初级和次级骨化过程,发育形成具有完整结构的髋关节。调节骨发育中成软骨和成骨过程的SOX9和RUNX2等因子受到HIF、WNT、FGF及PTHRP等一系列信号通路的调控作用介导髋关节的发育进程。通过临床DDH病例基因检测(全基因组测序及全外显子测序等)发现28个左右潜在的DDH致病基因,对揭示DDH发生的分子机制具有重要意义。最后,本文还探讨了DDH研究与治疗仍面临的挑战与未来可能需要重点关注的发展方向,以期为DDH发生机制的探讨与临床诊疗策略的制订提供新的思路。

关键词：发育性髋关节发育不良软骨内成骨诊疗策略小儿骨科早期筛查成软骨髋关节骨发育

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低氧诱导因子-1α在小鼠次级骨化中心形成中的表达

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上海医学 2007年第7期30卷 523-526,F0003页

作者：朱勋兵邓廉夫周琦上海交通大学医学院附属瑞金医院骨科上海市伤骨科研究所

目的研究低氧诱导因子-1α(HIF-1α)在小鼠肢体次级骨化中心形成阶段的时空表达规律,并探讨其在长骨次级骨化中心发生和发育过程中的作用。方法解剖镜下整体观察股骨次级骨化中心的发生、发展过程;以地高辛标记的HIF-1αcRNA为探针,采... 详细信息

目的研究低氧诱导因子-1α(HIF-1α)在小鼠肢体次级骨化中心形成阶段的时空表达规律,并探讨其在长骨次级骨化中心发生和发育过程中的作用。方法解剖镜下整体观察股骨次级骨化中心的发生、发展过程;以地高辛标记的HIF-1αcRNA为探针,采用组织切片原位杂交技术,观察HIF-1αmRNA在次级骨化中心形成阶段的时空表达规律;通过免疫组织化学法观察HIF-1α蛋白在次级骨化中心形成中的表达及分布。结果出生6d,在股骨髁部见到不透光的骨化影,提示次级骨化中心开始出现;其后不透光影在股骨髁内不断膨大。原位杂交显示,出生6d时股骨髁中心出现小片状荧光增强区,出生8d时荧光增强区呈放射样扩大,表示HIF-1αmRNA有大量表达。免疫组织化学法显示,出生6d时股骨髁中心少量HIF-1α蛋白表达,出生8d时次级骨化中心的细胞核内出现大量HIF-1α蛋白表达,之后很快消失。结论HIF-1α在次级骨化中心发育中呈规律性的时空表达,提示其可能参与小鼠长骨次级骨化中心形成的骨发育过程。

关键词：低氧诱导因子-1α 次级骨化小鼠

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骨质疏松发生的细胞学基础及其防治

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实用老年医学 2000年第3期14卷 119-121页

作者：邓廉夫上海第二医科大学瑞金医院上海市伤骨科研究所 200025

骨质疏松症以全身骨量减少及骨组织结构改变为主要病理特征,分为原发性和继发性,虽两者病因迥异,但基本病理改变相同;老年性骨折是其造成的主要危害之一.

关键词：骨质疏松细胞学基础病理防治

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Engineered extracellular vesicles for ischemic stroke treatment

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The Innovation 2023年第2期4卷 31-33页

作者： Huitong Ruan Yongfang Li Dandan Zheng lianfu deng Gang Chen Xingcai Zhang Yaohui Tang Wenguo Cui Jiaxing Key Laboratory of Basic Research and Clinical Translation on Orthopedic Biomaterials Department of OrthopaedicsThe Second Affiliated Hospital of Jiaxing UniversityJiaxing 314000China 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 RoadShanghai 200025China Department of Rehabilitation Medicine Ruijin HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200025China Med-X Research Institute and School of Biomedical Engineering Shanghai Jiao Tong UniversityShanghai 200030China School of Engineering and Applied Sciences Harvard UniversityCambridgeMA 02138USA

Dear Editor,Nanotechnology-based therapeutic strategies have been proven effective in diseases including cancer,infection,inflammation,etc.1 However,the application of nanotechnology is greatly restricted in the treatment of central nervous system(CNS)disorders due to physiological CNS *** example,the blood-brain barrier(BBB)can be the“Maginot line”for pharmacologically active molecules,blocking them out of the CNS.

关键词： inflammation treatment diseases

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股骨颈骨折的外科治疗及实验研究

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中华骨科杂志 1995年第3期15卷 145-148页

作者：孙从宪郭洪敏邓廉夫邢宝华山东省济宁市第一人民医院骨科济宁医学院解剖教研组

经临床及实验研究，作者认为传统三刃钉内固定术冶疗股骨颈骨折愈合率低的主要原因在于插钉本身不能有效的消除骨折后产生的剪切应力；骨折端的真正嵌插性复位是将剪切应力转变为压缩应力，是保证骨折愈合的关键因素。因此作者设计了股... 详细信息

经临床及实验研究，作者认为传统三刃钉内固定术冶疗股骨颈骨折愈合率低的主要原因在于插钉本身不能有效的消除骨折后产生的剪切应力；骨折端的真正嵌插性复位是将剪切应力转变为压缩应力，是保证骨折愈合的关键因素。因此作者设计了股骨颈“Ｕ”形截骨、头颈嵌插术治疗移位型股骨颈骨折６５例。经２年以上随访，骨折全部愈合，其中２例股骨头轻度坏死，晚期呈扁平髋。所有病例都行走自如，功能恢复满意，无其他并发症。

关键词：股骨颈骨折头颈嵌插术

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