BACKGROUND The translation from animal research into the clinical environment remains problematic, as animal systems do not adequately replicate the human in vivo environment. Bioreactors have emerged as a good alternative that can reproduce part of the human in vivo processes at an in vitro level. However, in vitro bone formation platforms primarily utilize stem cells only, with tissue based in vitro systems remaining poorly investigated. As such, the present pilot study explored the tissue behavior and cell survival capability within a new in vitro skeletal muscle tissue-based biomaterial organoid bioreactor system to maximize future bone tissue engineering prospects. RESULTS Three dimensional printed β-tricalcium phosphate/hydroxyapatite devices were either wrapped in a sheet of rat muscle tissue or first implanted in a heterotopic muscle pouch that was then excised and cultured in vitro for up to 30 days. Devices wrapped in muscle tissue showed cell death by day 15. Contrarily, devices in muscle pouches showed angiogenic and limited osteogenic gene expression tendencies with consistent TGF-ß1, COL4A1, VEGF-A, RUNX-2, and BMP-2 up-regulation, respectively. Histologically, muscle tissue degradation and fibrin release was seen being absorbed by devices acting possibly as a support for new tissue formation in the bioceramic scaffold that supports progenitor stem cell osteogenic differentiation. CONCLUSIONS These results therefore demonstrate that the skeletal muscle pouch-based biomaterial culturing system can support tissue survival over a prolonged culture period and represents a novel organoid tissue model that with further adjustments could generate bone tissue for direct clinical transplantations.

中文翻译：

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创伤使用基于肌肉生物材料的成骨类器官系统在体外诱导组织存活：概念研究的证明。

背景技术由于动物系统不能充分复制人体内环境，因此从动物研究到临床环境的翻译仍然存在问题。生物反应器已经成为一种很好的替代品，可以在体外水平上复制人类体内的部分过程。然而，体外骨形成平台主要仅利用干细胞，而基于组织的体外系统仍未得到充分研究。这样，当前的先导研究探索了一种新的基于体外骨骼肌组织的生物材料类器官生物反应器系统中的组织行为和细胞存活能力，以最大化未来的骨组织工程前景。结果将三维打印的β-磷酸三钙/羟基磷灰石装置包裹在大鼠肌肉组织中，或者首先植入异位肌肉袋中，然后将其切除并在体外培养长达30天。包裹在肌肉组织中的设备在第15天时会发生细胞死亡。相反，肌肉袋中的设备显示出血管生成和有限的成骨基因表达趋势，具有一致的TGF-ß1，COL4A1，VEGF-A，RUNX-2和BMP-2上调，分别。从组织学上看，肌肉组织降解和纤维蛋白释放被装置吸收，该装置可能充当支持祖细胞干细胞成骨分化的生物陶瓷支架中新组织形成的支持。