Upregulation of bone cell differentiation through immobilization within a synthetic extracellular matrix

Upregulation of bone cell differentiation through immobilization within a synthetic extracellular matrix
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DOI:
10.1016/j.biomaterials.2007.04.028
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发表时间:
2007-09-01
期刊:
影响因子:
14
通讯作者:
Granja, Pedro L.
Granja, Pedro L.
中科院分区:
工程技术1区
文献类型:
--
作者:
Evangelista, Marta B.;Hsiong, Susan X.;Granja, Pedro L.

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需要新的治疗策略来治疗由创伤、疾病或组织损失引起的骨缺损。用于细胞移植的可注射系统具有允许使用微创外科手术的优点,因此对患者的不适较少。在本研究中,假设Arg-Gly-Asp(RGD)偶联在二元(低和高分子量)可注射的藻酸盐组合物中能够影响三维(3D)结构中的骨细胞分化。固定化细胞的活力,代谢活性,细胞骨架组织,超微结构和分化(碱性磷酸酶(ALP),von Kossa,茜素红染色和骨钙素定量)进行了评估。RGD修饰的藻酸盐微球内的细胞能够与合成的细胞外基质建立更多的相互作用,如通过共聚焦激光扫描显微镜和透射电子显微镜成像所观察到的,并且当与固定在未修饰的藻酸盐微球内的细胞相比时,呈现出高得多的分化水平(更强烈的ALP和矿化染色以及更高水平的骨钙素分泌)。这些研究结果表明,共价偶联到藻酸盐的肽在影响细胞的行为在这个三维系统中是有效的,并可能提供足够的细胞移植成骨细胞的准备。(c)2007爱思唯尔有限公司保留所有权利。
There is a need for new therapeutic strategies to treat bone defects caused by trauma, disease or tissue loss. Injectable systems for cell transplantation have the advantage of allowing the use of minimally invasive surgical procedures, and thus for less discomfort to patients. In the present study, it is hypothesized that Arg-Gly-Asp (RGD)-coupled in a binary (low and high molecular weight) injectable alginate composition is able to influence bone cell differentiation in a three-dimensional (3D) structure. Viability, metabolic activity, cytoskeleton organization, ultrastructure and differentiation (alkaline phosphatase (ALP), von Kossa, alizarin red stainings and osteocalcin quantification) of immobilized cells were assessed. Cells within RGD-modified alginate microspheres were able to establish more interactions with the synthetic extracellular matrix as visualized by confocal laser scanning microscope and transmission electron microscopy imaging, and presented a much higher level of differentiation (more intense ALP and mineralization stainings and higher levels of osteocalcin secretion) when compared to cells immobilized within unmodified alginate microspheres. These findings demonstrate that peptides covalently coupled to alginate were efficient in influencing cell behavior within this 3D system, and may provide adequate preparation of osteoblasts for cell transplantation. (c) 2007 Elsevier Ltd. All rights reserved.