Macias Elioth, Yee-de León Juan F, Gonzalez-Vilchis Rosa Angelica, Cantoral-Sánchez Ariel, Flores-Loera Francisco Javier, Alvarez Mario Moisés, Santiago Grissel Trujillo-de, Ray Mallar, Madadelahi Masoud
School of Engineering and Sciences, Tecnologico de Monterrey, Monterrey, 64849, Nuevo León, Mexico.
Centro de Biotecnología-FEMSA, Tecnologico de Monterrey, 64849, Monterrey, Nuevo León, Mexico.
Microsyst Nanoeng. 2025 Aug 28;11(1):166. doi: 10.1038/s41378-025-01009-y.
Biopolymer core-shell microspheres play a crucial role in various biomedical applications, including drug delivery, tissue engineering, and diagnostics. These applications require microparticles with consistent, well-controlled size and precise shape fidelity. However, achieving high-throughput synthesis of size and shape-controlled core-shell biopolymer microgels remains a significant challenge. Herein, we present a one-step process for the high-throughput generation of monodisperse, luminescent, chitosan alginate core-shell microspheres by a novel manipulation of a centrifugal microfluidic device. We utilized the pH sensitivity of chitosan and the ionic gelation properties of alginate to create well-defined core-shell morphologies. To address particle merging issues and promote uniform particle size generation, we introduced an innovative pulsed mode operation in our centrifugal microfluidics device. We also incorporated fluorescent, nitrogen-functionalized graphene quantum dots into the core-shell structures, thereby rendering them useful for real-time imaging, which is necessary for diagnostic and therapeutic applications. To enhance biocompatibility, the alginate solution was supplemented with fish gelatin (FG). The resulting microspheres exhibited excellent structural integrity maintaining their core-shell structure after 15 days. Biocompatibility was demonstrated by C2C12 cell viability exceeding 88% after 15 days and by bacterial viability reaching the same percentage after 2 days. The system demonstrates considerable scalability, allowing for the consistent production of large quantities of microspheres without compromising functionality. The streamlined and efficient methodology simplifies the production process while unlocking new possibilities in targeted therapies, tissue regeneration, and diagnostics.
生物聚合物核壳微球在各种生物医学应用中发挥着关键作用，包括药物递送、组织工程和诊断。这些应用需要尺寸一致、可控且形状保真度精确的微粒。然而，实现尺寸和形状可控的核壳生物聚合物微凝胶的高通量合成仍然是一项重大挑战。在此，我们通过对离心微流控装置进行新颖的操作，提出了一种高通量生成单分散、发光的壳聚糖-海藻酸盐核壳微球的一步法。我们利用了壳聚糖的pH敏感性和海藻酸盐的离子凝胶化特性来创建明确的核壳形态。为了解决颗粒合并问题并促进均匀粒径的生成，我们在离心微流控装置中引入了创新的脉冲模式操作。我们还将荧光、氮功能化的石墨烯量子点纳入核壳结构，从而使其可用于实时成像，这对于诊断和治疗应用是必要的。为了提高生物相容性，海藻酸盐溶液中添加了鱼明胶（FG）。所得微球表现出优异的结构完整性，在15天后仍保持其核壳结构。15天后C2C12细胞活力超过88%以及2天后细菌活力达到相同百分比，证明了其生物相容性。该系统具有相当大的可扩展性，能够在不影响功能情况下持续生产大量微球。这种简化高效的方法简化了生产过程，同时为靶向治疗、组织再生和诊断开辟了新的可能性。
