Rapid fabrication of vascularized and innervated cell-laden bone models with biomimetic intrafibrillar collagen mineralization.,Nature Communications

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Rapid fabrication of vascularized and innervated cell-laden bone models with biomimetic intrafibrillar collagen mineralization.
Nature Communications ( IF 14.7 ) Pub Date : 2019-08-06 , DOI: 10.1038/s41467-019-11455-8
Greeshma Thrivikraman ₁ , Avathamsa Athirasala ₂ , Ryan Gordon ₃ , Limin Zhang ₃ , Raymond Bergan ₃ , Douglas R Keene ₄ , James M Jones ₅ , Hua Xie ₅ , Zhiqiang Chen ₆ , Jinhui Tao ₇ , Brian Wingender ₈ , Laurie Gower ₈ , Jack L Ferracane ₁ , Luiz E Bertassoni _{1,

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Affiliation

Bone tissue, by definition, is an organic-inorganic nanocomposite, where metabolically active cells are embedded within a matrix that is heavily calcified on the nanoscale. Currently, there are no strategies that replicate these definitive characteristics of bone tissue. Here we describe a biomimetic approach where a supersaturated calcium and phosphate medium is used in combination with a non-collagenous protein analog to direct the deposition of nanoscale apatite, both in the intra- and extrafibrillar spaces of collagen embedded with osteoprogenitor, vascular, and neural cells. This process enables engineering of bone models replicating the key hallmarks of the bone cellular and extracellular microenvironment, including its protein-guided biomineralization, nanostructure, vasculature, innervation, inherent osteoinductive properties (without exogenous supplements), and cell-homing effects on bone-targeting diseases, such as prostate cancer. Ultimately, this approach enables fabrication of bone-like tissue models with high levels of biomimicry that may have broad implications for disease modeling, drug discovery, and regenerative engineering.

中文翻译：

具有仿生纤维内胶原矿化作用的血管化和神经支配的载有骨的骨模型的快速制作。

骨组织，按照定义，是一种有机-无机纳米复合材料，其中代谢活性细胞嵌入在纳米级严重钙化的基质内。当前，没有能够复制这些骨组织确定性特征的策略。在这里，我们描述了一种仿生方法，其中将过饱和的钙和磷酸盐培养基与非胶原蛋白类似物结合使用，以引导纳米级磷灰石沉积在胶原蛋白的原纤维内和原纤维外空间中，其中胶原蛋白内嵌有骨祖细胞，血管和神经细胞。通过此过程，可以对骨骼模型进行工程设计，从而复制骨骼细胞和细胞外微环境的关键特征，包括其蛋白质引导的生物矿化，纳米结构，脉管系统，神经支配，固有的骨诱导特性（无外源性补充剂），以及对靶向骨的疾病（例如前列腺癌）的细胞归巢作用。最终，这种方法能够制造出具有高仿生水平的骨样组织模型，这可能对疾病建模，药物发现和再生工程产生广泛的影响。

更新日期：2019-08-06

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