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

立项年度

2016

立项时间

未公开

项目编号

11632013

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。

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  • 1.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

    ...
  • 2.Antibacterial hydroxyapatite coatings on titanium dental implants

    • 关键词:
    • composite; dental implant; hydroxyapatite; titanium; antibacterial;IN-VITRO BIOACTIVITY; COMPOSITE COATINGS; ELECTROPHORETIC DEPOSITION;CALCIUM-PHOSPHATE; POROUS TITANIUM; ELECTROCHEMICAL DEPOSITION;FLUORIDATED HYDROXYAPATITE; NANOPARTICLES; SURFACE; SILVER

    Titanium and its alloys are often used as substrates for dental implants due to their excellent mechanical properties and good biocompatibility. However, their ability to bind to neighboring bone is limited due to the lack of biological activity. At the same time, they show poor antibacterial ability which can easily cause bacterial infection and chronic inflammation, eventually resulting in implant failure. The preparation of composite hydroxyapatite coatings with antibacterial ability can effectively figure out these concerns. In this review, the research status and development trends of antibacterial hydroxyapatite coatings constructed on titanium and its alloys are analyzed and reviewed. This review may provide valuable reference for the preparation and application of high-performance and multi-functional dental implant coatings in the future.

    ...
  • 3.Progress in 3D printing for bone tissue engineering: a review

    • 关键词:
    • CALCIUM-PHOSPHATE; 3-DIMENSIONAL SCAFFOLD; 3D-PRINTED SCAFFOLDS;COMPOSITE SCAFFOLDS; IN-VITRO; IMPLANTS; HYDROGELS; STRENGTH;FABRICATION; DESIGN

    Effective clinical methods for large bone defects are not yet available on account of the complex intrinsic structure and mechanical characteristics of natural bone tissue. It remains a challenge to restore bone damage to its original form by tissue engineering. With the continuous development of three-dimensional (3D) printing in recent years, the emergence of new technical supports and material innovations has established the foundation for bone tissue engineering (BTE). 3D printing has significant advantages for personalized treatment, as it allows for the specific fabrication of scaffolds with appropriate size, shape and intrinsic structural characteristics via patients' computerized axial tomography scan or magnetic resonance imaging. In this review, we first systematically reviewed the development of 3D printing, printing methods and the selection of printing inks, then focused on the application of high-strength hydrogels in 3D printing for BTE. A brief anticipation of the future development of 3D printing was presented.[GRAPHICS].

    ...
  • 4.Alginate microgels as delivery vehicles for cell-based therapies in tissue engineering and regenerative medicine

    • 关键词:
    • Alginate; Microgels; Cell encapsulation; Cell delivery; Microfabrication;MESENCHYMAL STEM-CELLS; IN-VITRO; MICROFLUIDIC GENERATION; ISLETTRANSPLANTATION; APA MICROCAPSULES; BONE; HYDROGEL; MICROSPHERES;ENCAPSULATION; MICROBEADS

    Conventional stem cell delivery typically utilize administration of directly injection of allogenic cells or domesticated autogenic cells. It may lead to immune clearance of these cells by the host immune systems. Alginate microgels have been demonstrated to improve the survival of encapsulated cells and overcome rapid immune clearance after transplantation. Moreover, alginate microgels can serve as three-dimensional extracellular matrix to support cell growth and protect allogenic cells from rapid immune clearance, with functions as delivery vehicles to achieve sustained release of therapeutic proteins and growth factors from the encapsulated cells. Besides, cell-loaded alginate microgels can potentially be applied in regenerative medicine by serving as injectable engineered scaffolds to support tissue regrowth. In this review, the properties of alginate and different methods to produce alginate microgels are introduced firstly. Then, we focus on diverse applications of alginate microgels for cell delivery in tissue engineering and regenerative medicine.

    ...
  • 5.The fabrication of antibacterial hydrogels for wound healing

    • 关键词:
    • Antibacterial hydrogels; Fabrication; Antibacterial agents;Light-assisted antibacterial; Wound healing;ANTIMICROBIAL HYDROGELS; SILVER NANOPARTICLES; RAPID STERILIZATION;INJECTABLE HYDROGEL; HIGH-STRENGTH; CHITOSAN; ADHESIVE; HEMOSTASIS;PERFORMANCE; FIBERS

    Antimicrobial hydrogels have been proposed to be interesting materials used for wound healing due to their unique properties. Therefore, numerous scientists have made efforts to design and synthesize antibacterial hydrogels. At present, there are two commonly used methods for preparing antibacterial hydrogels. One is combining antibacterial agents with hydrogels. Antibacterial drugs include antibiotics, some biological extracts, natural polymers and some metal nanoparticles. In this review, physical combination (directly incorporating, swelling diffusion method, encapsulated in carriers) and chemical combination (hydrogels with inherent antibacterial activity, forming chemical bonds) are introduced depending on the methods and types of antibacterial agents incorporated with hydrogels. The other one is light-assisted antibacterial hydrogels, which involve photothermal antibacterial hydrogels and photo-dynamic antibacterial hydrogels. The common methods to prepare light-assisted antibacterial hydrogels are also described in this work. With the rapid improvements in antibacterial technology, many novel antibacterial hydrogels are constantly emerging. The most relevant studies and the latest status of research in this area were evaluated in this review.

    ...
  • 6.The fabrication of antibacterial hydrogels for wound healing

    • 关键词:
    • Antibacterial hydrogels; Fabrication; Antibacterial agents;Light-assisted antibacterial; Wound healing;ANTIMICROBIAL HYDROGELS; SILVER NANOPARTICLES; RAPID STERILIZATION;INJECTABLE HYDROGEL; HIGH-STRENGTH; CHITOSAN; ADHESIVE; HEMOSTASIS;PERFORMANCE; FIBERS

    Antimicrobial hydrogels have been proposed to be interesting materials used for wound healing due to their unique properties. Therefore, numerous scientists have made efforts to design and synthesize antibacterial hydrogels. At present, there are two commonly used methods for preparing antibacterial hydrogels. One is combining antibacterial agents with hydrogels. Antibacterial drugs include antibiotics, some biological extracts, natural polymers and some metal nanoparticles. In this review, physical combination (directly incorporating, swelling diffusion method, encapsulated in carriers) and chemical combination (hydrogels with inherent antibacterial activity, forming chemical bonds) are introduced depending on the methods and types of antibacterial agents incorporated with hydrogels. The other one is light-assisted antibacterial hydrogels, which involve photothermal antibacterial hydrogels and photo-dynamic antibacterial hydrogels. The common methods to prepare light-assisted antibacterial hydrogels are also described in this work. With the rapid improvements in antibacterial technology, many novel antibacterial hydrogels are constantly emerging. The most relevant studies and the latest status of research in this area were evaluated in this review.

    ...
  • 7.Alginate microgels as delivery vehicles for cell-based therapies in tissue engineering and regenerative medicine

    • 关键词:
    • Alginate; Microgels; Cell encapsulation; Cell delivery; Microfabrication;MESENCHYMAL STEM-CELLS; IN-VITRO; MICROFLUIDIC GENERATION; ISLETTRANSPLANTATION; APA MICROCAPSULES; BONE; HYDROGEL; MICROSPHERES;ENCAPSULATION; MICROBEADS

    Conventional stem cell delivery typically utilize administration of directly injection of allogenic cells or domesticated autogenic cells. It may lead to immune clearance of these cells by the host immune systems. Alginate microgels have been demonstrated to improve the survival of encapsulated cells and overcome rapid immune clearance after transplantation. Moreover, alginate microgels can serve as three-dimensional extracellular matrix to support cell growth and protect allogenic cells from rapid immune clearance, with functions as delivery vehicles to achieve sustained release of therapeutic proteins and growth factors from the encapsulated cells. Besides, cell-loaded alginate microgels can potentially be applied in regenerative medicine by serving as injectable engineered scaffolds to support tissue regrowth. In this review, the properties of alginate and different methods to produce alginate microgels are introduced firstly. Then, we focus on diverse applications of alginate microgels for cell delivery in tissue engineering and regenerative medicine.

    ...
  • 8.Iron Oxide Nanoparticles in the Application of Magnetic Resonance Imaging

    • 关键词:
    • iron oxide nanoparticles( IONP); surface modification; imagingmechanism; MRI application;MRI; BIOCOMPATIBILITY

    The application of Gd-based contrast agent is widely broad for magnetic resonance imaging in clinic diagnosis. However, the toxicity of Gd-based contrast agent still cannot be ignored. Therefore, most researchers have made a great effort to find low toxic contrast agent. lion oxide nanoparticles (IONP) have a great dark contrast effects in magnetic resonance imaging (MRI) due to their superparamagnetic properties , and they also have good biocompatibility. With the rapid development of biomaterials and molecular image technology, the application of IONP in MRI has become more and more broad. In recent years , IONP has made great progress in dual-modal imaging. What' s more, IONP is not only used to clinical diagnosis, but also in treatment. It offers some new strategies for the treatment of disease. Based on the magnetic resonance imaging mechanism and preparation, surface modification of IONP, this review elaborates the research progress of IONP in magnetic resonance imaging in recent years.

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  • 9.The Bonding Strength and Stability Between Hydroxyapatite Coating and Titanium or Titanium Alloys

    • 关键词:
    • titanium implant; HA coating; bonding strength; stability;CALCIUM-PHOSPHATE COATINGS; ELECTROPHORETIC DEPOSITION; COMPOSITE;TI-6AL-4V; IMPLANT; ADHESION; INTERFACE; SPRAY; FUNCTIONALIZATION;FABRICATION

    Titanium (Ti) and Ti alloys have been the main clinical application materials for bone and dental implants due to their excellent mechanical properties and good biocompatibility. However, it is not easy to achieve rapid osseointegration with surrounding bone tissues because of the biological inertia of titanium materials. Therefore, the biological activity of implant surface is further required. Hydroxyapatite (HA) is the main inorganic component of human bones and teeth, which has good bioactivity and biocompatibility. But restricted by its own brittleness, HA is often used as a coating material to cover the surface of Ti substrates to improve the biological activity of implants. However, the problems of weak bonding strength between coating and substrate and poor mechanical stability of coating have been the main factors limiting the wide clinical applications of HA coated titanium implants. From the aspects of coating structure, composition and preparation method, the research status and development trend of improving the interface bonding strength between Ti substrate and HA coating at home and abroad are summarized, which could provide a reference for the preparation and application of high-performance titanium implants.

    ...
  • 10.The Bonding Strength and Stability Between Hydroxyapatite Coating and Titanium or Titanium Alloys

    • 关键词:
    • titanium implant; HA coating; bonding strength; stability;CALCIUM-PHOSPHATE COATINGS; ELECTROPHORETIC DEPOSITION; COMPOSITE;TI-6AL-4V; IMPLANT; ADHESION; INTERFACE; SPRAY; FUNCTIONALIZATION;FABRICATION

    Titanium (Ti) and Ti alloys have been the main clinical application materials for bone and dental implants due to their excellent mechanical properties and good biocompatibility. However, it is not easy to achieve rapid osseointegration with surrounding bone tissues because of the biological inertia of titanium materials. Therefore, the biological activity of implant surface is further required. Hydroxyapatite (HA) is the main inorganic component of human bones and teeth, which has good bioactivity and biocompatibility. But restricted by its own brittleness, HA is often used as a coating material to cover the surface of Ti substrates to improve the biological activity of implants. However, the problems of weak bonding strength between coating and substrate and poor mechanical stability of coating have been the main factors limiting the wide clinical applications of HA coated titanium implants. From the aspects of coating structure, composition and preparation method, the research status and development trend of improving the interface bonding strength between Ti substrate and HA coating at home and abroad are summarized, which could provide a reference for the preparation and application of high-performance titanium implants.

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