骨组织细胞与软骨细胞响应力电微环境的力学生物学研究

项目来源

国家自然科学基金(NSFC)

项目主持人

陈维毅

项目受资助机构

太原理工大学

项目编号

11632013

立项年度

2016

立项时间

未公开

项目级别

国家级

研究期限

未知 / 未知

受资助金额

320.00万元

学科

数学物理科学-生物力学-多尺度力学生物学

学科代码

A-A10-A1002

基金类别

重点项目

关键词

力学微环境 ; 建模分析 ; 细胞—基质相互作用 ; 力学生物学响应 ; 力信号转导 ; mechanobiology response ; mechanotransduction ; cell-ECM interaction ; mechanical microenvironment ; model analysis

参与者

安美文;陈松;武晓刚;王楷群;黄棣;张全有;高志鹏;王艳芹

参与机构

太原理工大学

项目标书摘要:骨和软骨组织是人体重要的承载和运动器官。骨与软骨的再生和修复的研究对于临床上治疗骨损伤有着重要意义。骨与软骨的愈合和再生与所处微环境(如力、电、基质力学性质及拓扑结构等)紧密相关,但有关力电刺激影响骨组织细胞和软骨细胞生长的机理及刺激参数的优化、细胞与基质的相互作用等有待进一步研究。本项目基于二维电活性基底膜表面/三维电活性多孔基质材料,拟从不同维度开展骨组织细胞和软骨细胞对力电刺激响应的力学生物学研究;定量描述在力学微环境发生变化过程中,BK和TRPV4两类重要的力敏感离子通道协同调控软骨细胞感受基质微力学环境的分子机制;建立不同力电刺激下多孔基质材料内部微液流场模型,揭示力电耦合刺激对于骨组织生长的调控作用。项目将深入认识骨组织细胞和软骨细胞对力电微环境的响应机制,优化细胞—基质相互作用,为诱导相关细胞向预期功能发展提供参考,最终为骨与关节再生修复以及组织工程设计提供理论基础。

Application Abstract: Bone and cartilage are main complex tissues of human body for load bearing and motion.Regeneration and repair of bone and cartilage play crucial roles in clinical treatment of bone trauma.Microenvironments(e.g.electrical and mechanical stimulation,mechanical properties and topology of extracellular matrix)have significant effect on remodeling of bone and cartilage.However,the influence of mechanical and electrical stimulation on cells of bone and cartilage tissues remains challenging,and interaction between the cell and extracellular matrix are needed to further studied.In this project,main researches are shown in three respects.First,cellular mechanobiology of cells of bone and cartilage tissue responding to electrical and mechanical stimulation are probed from different scales based on electrical active matrix material;Second,a detailed work is developed for the quantification of the molecular profile that reflect how two important mechanosensitive ion channel,including BK and TRPV4,regulate the response of chondrocytes to changes in matrix mechanical microenvironment;Third,microfluid model of porous matrix material is developed to probe the regulation of combined mechanical and electrical stimulation on bone growth.This project facilitates to further understanding of response mechanism of cells of bone and cartilage to mechanical and electrical microenvironment,and optimizing interaction between cell and matrix,providing a solid ground for further investigation of induced targeted cellular function and a theoretical support of regeneration and of bone and joint and the design of tissue engineering.

项目受资助省

山西省

项目结题报告(全文)

骨和软骨组织是人体重要的承载和运动器官。骨与软骨的再生和修复的研究对于临床上治疗骨损伤有着重要意义。骨与软骨的愈合和再生与所处微环境(如力、电、基质力学性质及拓扑结构等)紧密相关,但有关力电刺激影响骨组织细胞和软骨细胞生长的机理及刺激参数的优化、细胞与基质的相互作用等有待进一步研究。本项目构建了三维电活性多孔基质材料,设计研制了多通道电刺激器,为不同维度开展骨组织细胞和软骨细胞对力电刺激响应的力学生物学研究提供了技术支撑;定量描述了在力学微环境发生变化过程中,PIEZOs和TRPV4两类重要的力敏感离子通道协同调控软骨细胞感受基质微力学环境的分子机制;建立了不同力电刺激下多孔基质材料内部微液流场模型,揭示了力电耦合刺激对于骨组织生长的调控作用。项目将深入认识骨组织细胞和软骨细胞对力电微环境的响应机制,优化细胞—基质相互作用,为诱导相关细胞向预期功能发展提供参考,最终为骨与关节再生修复以及组织工程设计提供理论基础。

  • 排序方式:
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  • 1.Gender Differences in Joint Biomechanics During Obstacle Crossing with Different Heights.

    • 关键词:
    • gait; gender; kinematics; kinetics; obstacles
    • Wang, Chenyan;Guo, Yuan;Du, Weijin;Li, Zhiqiang;Chen, Weiyi
    • 《Bioengineering 》
    • 2025年
    • 12卷
    • 2期
    • 期刊

    Identifying gender-related gait changes offers valuable insights into the role of gender in motor control. It is anticipated that more difficult gait tasks (obstacle crossing) may reveal gender-specific effects on gait parameters. The present study aimed to explore the gait adaptations of male and female participants when stepping over obstacles of 0 cm, 13 cm, 19 cm, and 26 cm in height. A total of 12 male and 12 female participants were recruited. The Vicon motion capture system and AMTI force plates were utilized to obtain the gait parameters. Moreover, spatiotemporal parameters were investigated. Two-way repeated ANOVA (gender * obstacle height) and three-way repeated ANOVA (gender * obstacle height * leg) were performed to compare gait parameters, respectively. Correlations between maximum joint angle and obstacle height were also evaluated. Significant interactions were observed for leading leg swing time, maximum hip extension angle, maximum knee flexion angle, and maximum ankle plantarflexion angle (gender * obstacle height). There were some differences in gait parameters between males and females in the unobstructed gait, and these changes became more evident as obstacle height increased. This study also identified significant differences in gait parameters between leading and trailing legs when stepping over the obstacle.

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  • 2.Effects of custom-made insole on the mechanical response characteristics of the foot during static standing and walking

    • 关键词:
    • ;Arch supports;Custom-make insole;Element method;Finite element analyse;Foot;Integral values;Metatarsal pad;Plantar fascia;Plantar pressures;Pressure-time integral
    • Wang, Chenyan;Du, Weijin;Li, Zhiqiang;Chen, Weiyi
    • 《Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine》
    • 2025年
    • 期刊

    Custom-made insoles are designed to redistribute foot load and prevent potential pain. Common methods to investigate the effectiveness of insoles include finite element method and experimental approach. However, most finite element research has focused on the two-dimensional plantar fascia stresses during static standing with insoles, rather than those of three-dimensional plantar fascia. Furthermore, the effects of insole with design parameters (metatarsal pad, toe pad, and arch support) on dynamic plantar pressures still need further exploration. Therefore, this study aimed to quantify the impact of custom-made insoles on foot biomechanics by combining both methods. Finite element method was employed to evaluate stress on the plantar fascia and bony structures when static standing, both barefoot and with a custom-made insole. Furthermore, 10 participants were recruited to investigate dynamic plantar pressures during walking barefoot and with insole. The relative time of four subphases during stance phase, total contact time, peak plantar pressure (Peak P), and pressure time integral (PTI) were assessed. Finite element results revealed reduced plantar fascia stresses and more uniform stress distribution over metatarsals and phalanges when standing with insole. Additionally, Peak P and PTI values in the second and third metatarsals were significantly lower when walking with insole. With the presence of insole, Peak P and PTI values in medial regions were significantly reduced, except for the midfoot region. In conclusion, custom-made insole with the addition of a metatarsal pad, toe pad, and arch support can effectively distribute foot tissue stress evenly, alleviate plantar pressure, and thus prevent pain. © IMechE 2025.

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  • 3.基于PVA的骨软骨组织工程双相水凝胶研究

    • 关键词:
    • 骨软骨损伤;骨关节病变;骨软骨组织工程;关节软骨;退行性疾病;仿生支架;界面结合力;水凝胶
    • 兰伟伟;黄棣;陈维毅
    • 《医用生物力学》
    • 期刊

    目的随着人口老龄化进程的日益加剧,由退行性疾病、不恰当运动方式以及骨关节病变等原因造成的骨软骨损伤病变的发生率在不断上升。介于骨软骨结构的复杂性和关节软骨自身缺少神经和血管,目前,临床上针对骨软骨损伤尚未有理想的治疗方式

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  • 4.纳米结构基底与细胞间相互作用对细胞行为及捕获的影响

    • 关键词:
    • 纳米阵列;CTCs;相互作用;细胞捕获;细胞行为;HeLa细胞
    • 孔金龙
    • 指导老师:太原理工大学 王楷群
    • 学位论文

    恶性肿瘤即癌症仍是目前难以根治的疾病,恶性肿瘤的无限增殖和极强的转移特性是其致命的主要原因,严重的危害着人类生命健康。循环肿瘤细胞(CTCs)是近十几年来研究应用的仅有的几个新型肿瘤分子标志物之一,可用于癌症检测,确诊和预后监控。但是基于抗体分离技术的临床应用因为不同细胞的靶抗原表达的异质性和差异性而受到限制。近年来随着纳米科学技术的发展以及组织工程学的进一步完善,许多纳米材料的研究已经逐步应用到生物医学、环境科学等多个领域。已有研究表明特定宽深比的纳米结构生长的基底表面是研究细胞过程并设计新颖的设备来控制细胞行为的有前途的工具,细胞和纳米结构基底之间的相互作用可以模拟肿瘤的生长所处的微环境,而微环境中的力学特性的改变和细胞的各种行为之间存在着一定联系。因此,有必要充分了解纳米材料的结构以及纳米材料细胞生长过程中的耦合关系,以充分利用其独特的特性。本论文通过等离子聚合技术制备了两种不同结构的纳米森林阵列,以HeLa细胞为例,研究了不同力学特性下的纳米阵列对与癌细胞捕获能力的影响,实验与有限元模拟数据显示本研究中制备的两种硅纳米森林阵列可对细胞进行不同弯曲特性的力学响应,从而产生不同力学刺激;随后评价了基底与癌细胞之间的相互作用对于细胞活性以及细胞行为的影响,结果表明硅纳米森林阵列改变了HeLa细胞粘附形态和迁移行为,NCW基底和NFCW基底对比普通硅片增大了2-3倍的细胞捕获效率,并且减少了20-30%细胞迁移效率;最后通过粘附蛋白Vinculin的表达分析了基底和细胞间的相互耦合作用,结果表明NCW基底Vinculin的表达数量是其他组的1.7-2倍,所以本研究分析Vinculin的高表达是NCW基底增强细胞捕获能力并且减少细胞迁移行为的主要原因。综上所述,纳米结构可以作为分离CTCs的有前途的方法,并与表面标记物的表达或CTCs的大小无关。本文所制备的一种特定纳米尺度形貌的硅纳米阵列可以增强与细胞之间的相互作用,可以在不另外使用捕获抗体的情况下提高细胞捕获效率,同时可以提供良好的生物相容性,保证捕获细胞的活性,有利于捕获细胞的后续检测表征。这项研究采选择出了一种优化的纳米形貌,为进一步改善细胞捕获效率提供有用的信息,这也为纳米基底的临床应用和癌症治疗提供了一些帮助。

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  • 5.Physically crosslinked poly(vinyl alcohol)-based hydrogels for cartilage tissue engineering

    • 关键词:
    • Biocompatibility;Biomechanics;Cartilage;Defects;Flavonoids;Hyaluronic acid;Organic acids;Polyvinyl alcohols;Restoration;Tissue regeneration;Cartilage defects;Cartilage regeneration;Chondrocytes;Defect repair;Icariin;Poly (vinyl alcohol) (PVA);Poly(vinyl alcohol);Poly(vinyl alcohol) (PVA);Tissues engineerings
    • Xiang, Changxin;Guo, Zijian;Zhang, Qing;Wang, Zehua;Li, Xiaona;Chen, Weiyi;Wei, Xiaochun;Li, Pengcui;Xiang, Chuan
    • 《Materials and Design》
    • 2024年
    • 243卷
    • 期刊

    Due to the limited self-healing ability of cartilage, cartilage defect repair remains a challenge in clinical treatment. Therefore, there is a need to provide patients with a promising cartilage defect repair strategy. In this study, we have reported an icariin-loaded PVA based biocompatible hydrogel scaffold for cartilage defect repair. The PTGH+Icariin hydrogel was prepared by a simple physical cross-linking method and consisted of polyvinyl alcohol (PVA), tannic acid (TA), gelatin (Gel), hyaluronic acid (HA) and icariin. Inspired by the natural cartilage matrix compositions, the Gel and HA were used to improve the bioactivity and biocompatibility of hydrogel. Furthermore, icariin was introduced to further enhance the hydrogel's ability for cartilage regeneration. The results showed that PTGH+icariin hydrogel exhibited porous microstructures and tough mechanical properties. In vitro cell experiments confirmed PTGH+Icariin hydrogels could promote chondrocytes proliferation, chondrocytes spreading and chondrocytes migration. Meanwhile, the PTGH+Icariin hydrogel demonstrated the ability to promote the cartilage regeneration in a rat cartilage defect model. In particular, the implantation of PTGH+Icariin hydrogel could facilitate the restoration of motor function in rats. This study will provide a potential approach for the treatment of cartilage defects. © 2024 The Authors

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  • 6.Electrohydrodynamic Direct-Writing Micro/Nanofibrous Architectures: Principle, Materials, and Biomedical Applications

    • 关键词:
    • architectures; biomaterials; biomedical applications;electrohydrodynamic direct-writing; micro/nanoscale;STEM-CELL DIFFERENTIATION; GUIDE CONDUITS NGCS; POLYCAPROLACTONESCAFFOLDS; ELECTROSPUN SCAFFOLDS; COMPOSITE SCAFFOLDS; POLYMERNANOFIBERS; FIBROUS SCAFFOLDS; HIGH-PRECISION; JET; FIBERS

    Electrohydrodynamic (EHD) direct-writing has recently gained attention as a highly promising additive manufacturing strategy for fabricating intricate micro/nanoscale architectures. This technique is particularly well-suited for mimicking the extracellular matrix (ECM) present in biological tissue, which serves a vital function in facilitating cell colonization, migration, and growth. The integration of EHD direct-writing with other techniques has been employed to enhance the biological performance of scaffolds, and significant advancements have been made in the development of tailored scaffold architectures and constituents to meet the specific requirements of various biomedical applications. Here, a comprehensive overview of EHD direct-writing is provided, including its underlying principles, demonstrated materials systems, and biomedical applications. A brief chronology of EHD direct-writing is provided, along with an examination of the observed phenomena that occur during the printing process. The impact of biomaterial selection and architectural topographic cues on biological performance is also highlighted. Finally, the major limitations associated with EHD direct-writing are discussed.EHD direct-writing has notable advantages for the controlled fabrication of micro/nanoscale architectures and particularly suitable for mimicking the extracellular matrix (ECM) present in biological tissue. Herein, a comprehensive overview of EHD direct-writing, including its evolution, principles, materials, and biomedical applications, is summarized. Meanwhile, the most relevant and recent advances related to biomedical applications impacted by biomaterial selection and architectural topographic cues are highlighted. Finally, perspectives on the challenges of EHD direct-writing and its prospects for future development are discussed. image

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  • 7.Tough physically crosslinked poly(vinyl alcohol)-based hydrogels loaded with collagen type I to promote bone regeneration in vitro and in vivo

    • 关键词:
    • Bone regeneration; Mechanical properties; Physically crosslinkedhydrogel; Poly(vinyl alcohol);MESENCHYMAL STEM-CELLS; TANNIC-ACID; OSTEOGENIC DIFFERENTIATION;ACTIVATION; PATHWAY
    • Xiang, Changxin;Wang, Zehua;Zhang, Qing;Guo, Zijian;Li, Xiaona;Chen, Weiyi;Wei, Xiaochun;Li, Pengcui
    • 《INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES》
    • 2024年
    • 261卷
    • 期刊

    Poly(vinyl alcohol) (PVA) hydrogels exhibit great potential as ideal biomaterials for tissue engineering, owing to their non-toxicity, high water content, and strong biocompatibility. However, limited mechanical strength and low bioactivity have constrained their application in bone tissue engineering. In this study, we have developed a tough PVA-based hydrogel using a facile physical crosslinking method, comprising of PVA, tannic acid (TA), and hydroxyapatite (HA). Systematic experiments were conducted to examine the physicochemical properties of PVA/HA/TA hydrogels, including their compositions, microstructures, and mechanical and rheological properties. The results demonstrated that the PVA/HA/TA hydrogels possessed the porous microstructures and excellent mechanical properties. Furthermore, collagen type I (Col-I) was used to further improve the biocompatibility and bioactivity of PVA/HA/TA hydrogels. In vitro experiments revealed that PVA/HA/TA/COL hydrogel could offer a suitable microenvironment for the growth of MC3T3-E1 cells and promote their osteogenic differentiation. Meanwhile, the PVA/HA/TA/COL hydrogel demonstrated the ability to promote bone regeneration and osteointegration in a rat femoral defect model. This study provides a potential strategy for the use of PVA-based hydrogels in bone tissue engineering.

    ...
  • 8.Synthesis, in vitro biocompatibility and antibacterial property of novel silk fibroin@Ag spheres

    • 关键词:
    • Biocompatibility;Escherichia coli;Glass ceramics;Microstructure;Morphology;Silver nanoparticles;Synthesis (chemical);Antibacterial properties;Composites material;In-situ growth;In-vitro;SEM observation;Silk fibroin;Spherical morphologies;Synthesised;TEM observations;Vitro biocompatibilities
    • Zhang, Jianan;Zhao, Jie;Chen, Song;Jiao, Xiong;Li, Xiaona;Chen, Weiyi
    • 《Materials Letters》
    • 2024年
    • 357卷
    • 期刊

    In this study, novel silk fibroin@Ag spheres were synthesized by in situ growth of Ag nanoparticles (NPs) on silk fibroin (SF) spheres and their microstructure, in vitro biocompatibility, and antibacterial property were evaluated. SEM observation showed that SF@Ag spheres had a spherical morphology with a diameter of 1–10 µm. TEM observation revealed that each SF@Ag sphere had a dense structure and its surface was deposited with Ag NPs with a diameter of 10–50 nm. In vitro biocompatibility evaluation indicated that SF@Ag spheres were not cytotoxic when incubated with osteoblast MC3T3-E1 cells. Moreover, when exposed to two representative types of gram-negative Escherichia coli and gram-positive Staphylococcus aureus, SF@Ag spheres showed a good antibacterial property against the growth of both types of bacteria. © 2023 Elsevier B.V.

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  • 9.Biomechanical response of lower limb joints to lateral wedge insoles.

    • Du, Weijin;Guo, Yuan;Wang, Chenyan;Cui, Weiling;Chen, Weiyi;Li, Xiaona
    • 《Scientific reports》
    • 2024年
    • 14卷
    • 1期
    • 期刊

    Lateral wedge insole (LWI) is a frequently recommended treatment option for early and midterm stages of medial knee osteoarthritis. However, studies of its effects on the lower limb joints are incomplete and imperfect. The main purpose of this study was to quantitatively analyze the response of intervention of LWI on lower-limb joint kinematics, ground reaction forces (GRFs), and centre of pressure (COP). Gait analysis of 16 healthy subjects was conducted. Three-dimensional motion data and force plate measurements were collected in the control (barefoot) and experimental conditions (wearing a pair of assigned shoes with 0, 7, and 10mm LWIs). Results showed that the peak knee flexion angle was increased by 3.43°, 3.09°, and 3.27° with 0, 7, and 10mm LWIs, respectively (p<0.01). The ankle peak dorsiflexion angle was significantly decreased by 3.79°, 2.19°, and 1.66° with 0, 7, and 10mm LWIs, respectively (p=0.02). The internal rotation angle was increased by 2.78°, 3.76°, and 4.58° with 0, 7, and 10mm LWIs, respectively (p<0.01). The forefoot with LWIs showed highly significantly smaller inversion, eversion, and adduction angles (all p<0.01). The 1st peak of the vertical GRF (p=0.016) also increased significantly by a maximum of 0.06 body weight (BW) with LWIs. These results indicated that biomechanical changes and limitations of lateral wedges insole should be analyzed in more detail, possibly leading to new guidelines for the design and application. © 2024. The Author(s).

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  • 10.弯矩作用下姿势性脊柱后凸的生物力学响应

    • 关键词:
    • 姿势性脊柱后凸;有限元分析;生物力学;脊柱;COBB角
    • 王磊;王晨艳;郭媛;李晓娜;陈维毅
    • 《中国组织工程研究》
    • 2024年
    • 24期
    • 期刊

    背景:关于脊柱后凸的生物力学研究大多集中在躯干肌肉力量以及矢状面平衡等方面,关于脊柱后凸过程中脊柱内部的生物力学响应鲜有报道。目的:通过模拟姿势性脊柱后凸过程,探究姿势性脊柱后凸过程中脊柱的生物力学响应。方法:建立正常人

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