Magnetically actuated tissue engineered scaffold: insights into mechanism of physical stimulation.
Magnetically actuated tissue engineered scaffold: insights into mechanism of physical stimulation.
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DOI：
10.1039/c5nr05500h
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发表时间：
2016-02-14
期刊：
影响因子：
6.7
通讯作者：
Cohen S
中科院分区：
文献类型：
--
作者：
Sapir-Lekhovitser Y;Rotenberg MY;Jopp J;Friedman G;Polyak B;Cohen S
提供正确的刺激条件，在体外和体内产生有效的组织促进微环境是再生医学组织发育的最终目标之一。已经表明，除了分子信号（例如生长因子）之外，物理信号也是产生功能性细胞构建体所需要的。这些线索与生物组织的工程化特别相关，在生物组织中，机械应力激活机械敏感性受体，启动导致功能成熟组织产生的生化途径。与嵌入三维（3D）支架结构内的可磁化纳米颗粒偶联的均匀磁场远程地产生瞬时物理力，该瞬时物理力可以转移到紧邻纳米颗粒存在的细胞。本研究探讨了磁响应藻酸盐支架在均匀磁场中由于支架壁的排列而发生可逆形状变形的假设。使用定制的适合于原子力显微镜的亥姆霍兹线圈装置，我们原位监测基质尺寸的变化作为施加的磁场、支架壁结构内磁性颗粒的浓度和基质的刚度的函数。我们的研究结果表明，磁响应支架暴露于外部施加的时变均匀磁场进行可逆的形状变形。这表明，由于支架壁对齐和松弛的交替模式，产生弯曲/拉伸力的可能性不大，该弯曲/拉伸力可能对细胞施加机械效应。我们认为，矩阵结构的变形是由固定的磁性纳米粒子在矩阵壁导致在磁化后的支架壁的集体对齐。在实验条件下，可以赋予在支架壁上生长的细胞的估计机械力大约为1 pN，这与报道的在细胞水平上诱导机械转导效应的阈值很好地相关。这项工作是我们了解如何准确地创造适当的刺激微环境，促进细胞组织形成成熟的组织工程构建体的下一步。
Providing the right stimulatory conditions resulting in efficient tissue promoting microenvironment in vitro and in vivo is one of the ultimate goals in tissue development for regenerative medicine. It has been shown that in addition to molecular signals (e.g. growth factors) physical cues are also required for generation of functional cell constructs. These cues are particularly relevant to engineering of biological tissues, within which mechanical stress activates mechano-sensitive receptors, initiating biochemical pathways which lead to the production of functionally mature tissue. Uniform magnetic fields coupled with magnetizable nanoparticles embedded within three dimensional (3D) scaffold structures remotely create transient physical forces that can be transferrable to cells present in close proximity to the nanoparticles. This study investigated the hypothesis that magnetically responsive alginate scaffold can undergo reversible shape deformation due to alignment of scaffold’s walls in a uniform magnetic field. Using custom made Helmholtz coil setup adapted to an Atomic Force Microscope we monitored changes in matrix dimensions in situ as a function of applied magnetic field, concentration of magnetic particles within the scaffold wall structure and rigidity of the matrix. Our results show that magnetically responsive scaffolds exposed to an externally applied time-varying uniform magnetic field undergo a reversible shape deformation. This indicates on possibility of generating bending/stretching forces that may exert a mechanical effect on cells due to alternating pattern of scaffold wall alignment and relaxation. We suggest that the matrix structure deformation is produced by immobilized magnetic nanoparticles within the matrix walls resulting in a collective alignment of scaffold walls upon magnetization. The estimated mechanical force that can be imparted on cells grown on the scaffold wall at experimental conditions is in the order of 1 pN, which correlates well with reported threshold to induce mechanotransduction effects on cellular level. This work is our next step in understanding of how to accurately create proper stimulatory microenvironment for promotion of cellular organization to form mature tissue engineered constructs.