Fischetti Tiziana, Borciani Giorgia, Avnet Sofia, Rubini Katia, Baldini Nicola, Graziani Gabriela, Boanini Elisa
IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy.
Department of Biomedical and Neuromotor Sciences, University of Bologna, 40138 Bologna, Italy.
Nanomaterials (Basel). 2023 Jul 10;13(14):2040. doi: 10.3390/nano13142040.
Reproducing in vitro a model of the bone microenvironment is a current need. Preclinical in vitro screening, drug discovery, as well as pathophysiology studies may benefit from in vitro three-dimensional (3D) bone models, which permit high-throughput screening, low costs, and high reproducibility, overcoming the limitations of the conventional two-dimensional cell cultures. In order to obtain these models, 3D bioprinting offers new perspectives by allowing a combination of advanced techniques and inks. In this context, we propose the use of hydroxyapatite nanoparticles, assimilated to the mineral component of bone, as a route to tune the printability and the characteristics of the scaffold and to guide cell behavior. To this aim, both stoichiometric and Sr-substituted hydroxyapatite nanocrystals are used, so as to obtain different particle shapes and solubility. Our findings show that the nanoparticles have the desired shape and composition and that they can be embedded in the inks without loss of cell viability. Both Sr-containing and stoichiometric hydroxyapatite crystals permit enhancing the printing fidelity of the scaffolds in a particle-dependent fashion and control the swelling behavior and ion release of the scaffolds. Once Saos-2 cells are encapsulated in the scaffolds, high cell viability is detected until late time points, with a good cellular distribution throughout the material. We also show that even minor modifications in the hydroxyapatite particle characteristics result in a significantly different behavior of the scaffolds. This indicates that the use of calcium phosphate nanocrystals and structural ion-substitution is a promising approach to tune the behavior of 3D bioprinted constructs.
在体外重现骨微环境模型是当前的需求。临床前体外筛选、药物发现以及病理生理学研究可能会受益于体外三维（3D）骨模型，该模型允许高通量筛选、低成本且具有高重现性，克服了传统二维细胞培养的局限性。为了获得这些模型，3D生物打印通过结合先进技术和墨水提供了新的视角。在这种背景下，我们提议使用与骨矿物质成分相似的羟基磷灰石纳米颗粒，作为调节可打印性、支架特性并引导细胞行为的途径。为此，使用了化学计量比的和锶取代的羟基磷灰石纳米晶体，以获得不同的颗粒形状和溶解度。我们的研究结果表明，纳米颗粒具有所需的形状和组成，并且可以嵌入墨水中而不损失细胞活力。含锶和化学计量比的羟基磷灰石晶体都能够以颗粒依赖的方式提高支架的打印保真度，并控制支架的溶胀行为和离子释放。一旦将Saos-2细胞封装在支架中，在较晚时间点之前都能检测到较高的细胞活力，且细胞在整个材料中分布良好。我们还表明，即使羟基磷灰石颗粒特性的微小变化也会导致支架行为的显著不同。这表明使用磷酸钙纳米晶体和结构离子取代是调节3D生物打印构建体行为的一种有前途的方法。
