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Cartilage regeneration with dual-drug-releasing injectable hydrogel/microparticle system: In vitro and in vivo study.
Journal of Cellular Physiology ( IF 4.5 ) Pub Date : 2020-08-10 , DOI: 10.1002/jcp.30006 Ziba Naghizadeh 1 , Akbar Karkhaneh 1 , Hanieh Nokhbatolfoghahaei 2 , Saeed Farzad-Mohajeri 3 , Maryam Rezai-Rad 2 , Mohammad M Dehghan 3, 4 , Pouyan Aminishakib 5 , Arash Khojasteh 6
Journal of Cellular Physiology ( IF 4.5 ) Pub Date : 2020-08-10 , DOI: 10.1002/jcp.30006 Ziba Naghizadeh 1 , Akbar Karkhaneh 1 , Hanieh Nokhbatolfoghahaei 2 , Saeed Farzad-Mohajeri 3 , Maryam Rezai-Rad 2 , Mohammad M Dehghan 3, 4 , Pouyan Aminishakib 5 , Arash Khojasteh 6
Affiliation
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In this study, we developed an injectable in situ forming hydrogel/microparticle system consisting of two drugs, melatonin and methylprednisolone, to investigate the capability of the system for chondrogenesis in vitro and in vivo. The chemical, mechanical, and rheological properties of the hydrogel/microparticle were investigated. For in vitro evaluation, the adipose‐derived stem cells might be mixed with hydrogel/microparticles, then cellular viability was analyzed by acridine orange/propidium iodide and 4′,6‐diamidino‐2‐phenylindole staining and also dimethylmethylene blue assay were conducted to find the amount of proteoglycan. The real‐time polymerase chain reaction for aggrecan, sex‐determining region Y–Box 9, collagen I (COL1), and COL2 gene expression was performed after 14 and 21 days. For evaluation of cartilage regeneration, the samples were implanted in rabbit knees with cartilaginous experimental defects. Defects were created in both knees of three groups of rabbits. Group 1 was the control with no injection, and Groups 2 and 3 were loaded with hydrogel/cell and hydrogel/microparticle/cell; respectively. Then, after 3 and 6 months, histological evaluations of the defected sites were carried out. The amount of glycosaminoglycans after 14 and 21 days increased significantly in hydrogels/microparticles loaded with cells. The expression of marker genes was also significant in hydrogels/microparticles loaded with cells. According to histology analysis, the hydrogels/microparticles loaded with cells showed the best cartilage regeneration. Overall, our study revealed that the developed injectable hydrogel/microparticle can be used for cartilage regeneration.
中文翻译：
双药物释放可注射水凝胶/微粒系统的软骨再生：体外和体内研究。
在这项研究中，我们开发了一种可注射的原位形成水凝胶/微粒系统，由两种药物，褪黑激素和甲基强的松龙组成，以研究该系统在体外和体内的软骨形成能力。研究了水凝胶/微粒的化学、机械和流变学特性。对于体外评估，脂肪来源的干细胞可能与水凝胶/微粒混合，然后通过吖啶橙/碘化丙啶和 4',6-二脒基-2-苯基吲哚染色和二甲基亚甲基蓝测定分析细胞活力。找出蛋白多糖的数量。蛋白聚糖、性别决定区 Y-Box 9、胶原蛋白 I (COL1) 和 COL2 基因表达的实时聚合酶链反应在 14 天和 21 天后进行。对于软骨再生的评估，将样品植入具有软骨实验缺陷的兔膝关节。三组兔子的双膝均出现缺陷。第1组为未注射对照组，第2组和第3组分别加载水凝胶/细胞和水凝胶/微粒/细胞；分别。然后，在 3 个月和 6 个月后，对缺陷部位进行组织学评估。14 天和 21 天后，在装载有细胞的水凝胶/微粒中，糖胺聚糖的量显着增加。标记基因的表达在装载有细胞的水凝胶/微粒中也很重要。根据组织学分析，装载有细胞的水凝胶/微粒显示出最好的软骨再生。总的来说，我们的研究表明，开发的可注射水凝胶/微粒可用于软骨再生。
更新日期：2020-08-10
中文翻译：
双药物释放可注射水凝胶/微粒系统的软骨再生：体外和体内研究。
在这项研究中，我们开发了一种可注射的原位形成水凝胶/微粒系统，由两种药物，褪黑激素和甲基强的松龙组成，以研究该系统在体外和体内的软骨形成能力。研究了水凝胶/微粒的化学、机械和流变学特性。对于体外评估，脂肪来源的干细胞可能与水凝胶/微粒混合，然后通过吖啶橙/碘化丙啶和 4',6-二脒基-2-苯基吲哚染色和二甲基亚甲基蓝测定分析细胞活力。找出蛋白多糖的数量。蛋白聚糖、性别决定区 Y-Box 9、胶原蛋白 I (COL1) 和 COL2 基因表达的实时聚合酶链反应在 14 天和 21 天后进行。对于软骨再生的评估，将样品植入具有软骨实验缺陷的兔膝关节。三组兔子的双膝均出现缺陷。第1组为未注射对照组，第2组和第3组分别加载水凝胶/细胞和水凝胶/微粒/细胞；分别。然后，在 3 个月和 6 个月后，对缺陷部位进行组织学评估。14 天和 21 天后，在装载有细胞的水凝胶/微粒中，糖胺聚糖的量显着增加。标记基因的表达在装载有细胞的水凝胶/微粒中也很重要。根据组织学分析，装载有细胞的水凝胶/微粒显示出最好的软骨再生。总的来说，我们的研究表明，开发的可注射水凝胶/微粒可用于软骨再生。
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