Calcium phosphate (CaP) biomaterials are amongst the most widely used synthetic bone graft substitutes, owing to their chemical similarities to the mineral part of bone matrix and off-the-shelf availability. However, their ability to regenerate bone in critical-sized bone defects has remained inferior to the gold standard autologous bone. Hence, there is a need for methods that can be employed to efficiently produce CaPs with different properties, enabling the screening and consequent fine-tuning of the properties of CaPs towards effective bone regeneration. To this end, we propose the use of droplet microfluidics for rapid production of a variety of CaP microparticles. Particularly, this study aims to optimize the steps of a droplet microfluidic-based production process, including droplet generation, in-droplet CaP synthesis, purification and sintering, in order to obtain a library of CaP microparticles with fine-tuned properties. The results showed that size-controlled, monodisperse water-in-oil microdroplets containing calcium- and phosphate-rich solutions can be produced using a flow-focusing droplet-generator microfluidic chip. We optimized synthesis protocols based on in-droplet mineralization to obtain a range of CaP microparticles without and with inorganic additives. This was achieved by adjusting synthesis parameters, such as precursor concentration, pH value, and aging time, and applying heat treatment. In addition, our results indicated that the synthesis and fabrication parameters of CaPs in this method can alter the microstructure and the degradation behavior of CaPs. Overall, the results highlight the potential of the droplet microfluidic platform for engineering CaP microparticle biomaterials with fine-tuned properties.

中文翻译：

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使用基于液滴的微流控平台优化快速生产磷酸钙微粒的可调工艺

磷酸钙 (CaP) 生物材料是最广泛使用的合成骨移植替代品之一，因为它们的化学性质与骨基质的矿物质部分相似，而且易于使用。然而，它们在临界尺寸骨缺损中再生骨的能力仍然不如金标准自体骨。因此，需要可用于有效生产具有不同特性的CaP的方法，从而能够筛选和随后微调CaP的特性以实现有效的骨再生。为此，我们建议使用液滴微流控技术来快速生产各种CaP微粒。特别是，本研究旨在优化基于液滴微流控的生产过程的步骤，包括液滴生成、液滴内CaP合成、纯化和烧结，以获得具有微调特性的CaP微粒库。结果表明，使用流动聚焦液滴发生器微流控芯片可以产生含有富含钙和磷酸盐溶液的尺寸受控的单分散油包水微滴。我们基于液滴内矿化优化了合成方案，以获得一系列不含和含有无机添加剂的 CaP 微粒。这是通过调整合成参数（例如前体浓度、pH 值和老化时间）以及应用热处理来实现的。此外，我们的结果表明，该方法中 CaP 的合成和制造参数可以改变 CaP 的微观结构和降解行为。总体而言，这些结果凸显了液滴微流控平台在设计具有微调特性的 CaP 微粒生物材料方面的潜力。