Some biomaterials are osteoinductive, that is, they are able to trigger the osteogenic process by inducing the differentiation of mesenchymal stem cells to the osteogenic lineage. Although the underlying mechanism is still unclear, microporosity and specific surface area (SSA) have been identified as critical factors in material-associated osteoinduction. However, only sintered ceramics, which have a limited range of porosities and SSA, have been analyzed so far. In this work, we were able to extend these ranges to the nanoscale, through the foaming and 3D-printing of biomimetic calcium phosphates, thereby obtaining scaffolds with controlled micro- and nanoporosity and with tailored macropore architectures. Calcium-deficient hydroxyapatite (CDHA) scaffolds were evaluated after 6 and 12 weeks in an ectopic-implantation canine model and compared with two sintered ceramics, biphasic calcium phosphate and β-tricalcium phosphate. Only foams with spherical, concave macropores and not 3D-printed scaffolds with convex, prismatic macropores induced significant ectopic bone formation. Among them, biomimetic nanostructured CDHA produced the highest incidence of ectopic bone and accelerated bone formation when compared with conventional microstructured sintered calcium phosphates with the same macropore architecture. Moreover, they exhibited different bone formation patterns; in CDHA foams, the new ectopic bone progressively replaced the scaffold, whereas in sintered biphasic calcium phosphate scaffolds, bone was deposited on the surface of the material, progressively filling the pore space. In conclusion, this study demonstrates that the high reactivity of nanostructured biomimetic CDHA combined with a spherical, concave macroporosity allows the pushing of the osteoinduction potential beyond the limits of microstructured calcium phosphate ceramics.

中文翻译：

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泡沫和3D打印的磷酸钙支架的成骨作用：纳米结构和孔结构的影响。

一些生物材料具有骨诱导性，也就是说，它们能够通过诱导间充质干细胞向成骨细胞系的分化来触发成骨过程。尽管尚不清楚其基本机制，但已将微孔性和比表面积（SSA）确定为与材料相关的骨诱导的关键因素。但是，到目前为止，仅对孔隙率和SSA范围有限的烧结陶瓷进行了分析。在这项工作中，我们能够通过仿生磷酸钙的发泡和3D打印将这些范围扩展到纳米级，从而获得具有可控的微孔和纳米孔度以及量身定制的大孔结构的支架。在异位植入犬模型中6周和12周后评估缺钙的羟基磷灰石（CDHA）支架，并将其与两种烧结陶瓷双相磷酸钙和β-磷酸三钙进行比较。只有具有球形，凹形大孔的泡沫，而不是具有凸形，棱形大孔的3D打印支架，才会引起明显的异位骨形成。其中，与具有相同大孔结构的常规微结构烧结磷酸钙相比，仿生纳米结构CDHA产生异位骨的发生率最高，并加速了骨形成。而且，它们表现出不同的骨形成模式。在CDHA泡沫中，新的异位骨逐渐取代了支架，而在烧结的双相磷酸钙支架中，骨骼沉积在了材料的表面，逐渐填充毛孔空间。总之，这项研究表明，纳米结构仿生CDHA的高反应性与球形凹大孔相结合，可以将骨诱导潜力推向超出微结构磷酸钙陶瓷极限的范围。