Division of Biomechanics and Engineering Design, KU Leuven, Celestijnenlaan 300 C, Bus 2419, 3001 Heverlee, Belgium.
Acta Biomater. 2011 Oct;7(10):3573-85. doi: 10.1016/j.actbio.2011.06.021. Epub 2011 Jun 23.
Bone formation is a very complex physiological process, involving the participation of many different cell types and regulated by countless biochemical, physical and mechanical factors, including naturally occurring or synthetic biomaterials. For the latter, calcium phosphate (CaP)-based scaffolds have proven to stimulate bone formation, but at present still result in a wide range of in vivo outcomes, which is partly related to the suboptimal use and combination with osteogenic cells. To optimize CaP scaffold selection and make their use in combination with cells more clinically relevant, this study uses an integrative approach in which mathematical modeling is combined with experimental research. This paper describes the development and implementation of an experimentally informed bioregulatory model of the effect of calcium ions released from CaP-based biomaterials on the activity of osteogenic cells and mesenchymal stem cell driven ectopic bone formation. The amount of bone formation predicted by the mathematical model corresponds to the amount measured experimentally under similar conditions. Moreover, the model is also able to qualitatively predict the experimentally observed impaired bone formation under conditions such as insufficient cell seeding and scaffold decalcification. A strategy was designed in silico to overcome the negative influence of a low initial cell density on the bone formation process. Finally, the model was applied to design optimal combinations of calcium-based biomaterials and cell culture conditions with the aim of maximizing the amount of bone formation. This work illustrates the potential of mathematical models as research tools to design more efficient and cell-customized CaP scaffolds for bone tissue engineering applications.
骨形成是一个非常复杂的生理过程，涉及许多不同类型的细胞参与，并受无数生化、物理和机械因素的调节，包括天然或合成的生物材料。对于后者，磷酸钙（CaP）基支架已被证明能刺激骨形成，但目前仍导致广泛的体内结果，这部分与成骨细胞的使用不当和组合有关。为了优化 CaP 支架的选择，并使它们与细胞的结合更具临床相关性，本研究采用了一种综合方法，将数学建模与实验研究相结合。本文描述了一种从 CaP 基生物材料中释放的钙离子对成骨细胞活性和间充质干细胞驱动异位骨形成的影响的实验信息生物调节模型的开发和实施。数学模型预测的骨形成量与相似条件下实验测量的量相对应。此外，该模型还能够定性地预测在细胞接种不足和支架脱钙等条件下观察到的骨形成受损的情况。设计了一种在计算机上的策略，以克服低初始细胞密度对骨形成过程的负面影响。最后，该模型被应用于设计基于钙的生物材料和细胞培养条件的最佳组合，目的是最大限度地增加骨形成量。这项工作说明了数学模型作为研究工具的潜力，可用于设计更高效和细胞定制的 CaP 支架，用于骨组织工程应用。
