Ma Rong, Sun Jihpeng, Park Sungwan, Nikolla Fiona, Liu Albert Tianxiang
Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan 48109, United States.
Department of Materials Science and Engineering, University of Michigan, Ann Arbor, Michigan 48109, United States.
Chem Bio Eng. 2025 Apr 24;2(5):312-321. doi: 10.1021/cbe.5c00017. eCollection 2025 May 22.
Hydrogel-based drug delivery systems hold significant clinical potential by enabling precise spatial and temporal control over therapeutic release, ranging from metabolites, macromolecules to other cellular and subcellular constructs. However, achieving programmable release of payloads with diverse molecular weights at distinct rates typically requires complex polymer designs that can compromise the accessibility and biocompatibility of the delivery system. We present a scalable method for producing injectable, micrometer-scale alginate hydrogel particles (microgels) with precisely tuned microstructures for multiplexed, programmable cargo release. Our approach integrates an established jetting technique with a simple postsynthesis ion-exchange process to fine-tune the cross-linked microstructure of alginate microgels. By varying cation type (Ca, Mg, Na) and concentration, we systematically modulate the microgels' chemical and physical properties to control release rates of model compounds, including rhodamine B, methylene blue, and dextrans of various molecular weights. Additionally, a PEG-alginate composite microgel system is used to demonstrate the pre-programmed stepwise release of rhodamine B. These findings offer a straightforward strategy for postsynthetic manipulation of ionic microgels with controllable release performances, paving the way for advanced biomedical applications.
基于水凝胶的药物递送系统具有巨大的临床潜力，能够实现对治疗性释放的精确时空控制，释放范围涵盖代谢物、大分子以及其他细胞和亚细胞结构。然而，要以不同速率实现具有不同分子量的有效载荷的可编程释放，通常需要复杂的聚合物设计，这可能会损害递送系统的可及性和生物相容性。我们提出了一种可扩展的方法，用于生产具有精确调谐微观结构的可注射微米级藻酸盐水凝胶颗粒（微凝胶），以实现多重可编程的货物释放。我们的方法将一种成熟的喷射技术与一个简单的合成后离子交换过程相结合，以微调藻酸盐微凝胶的交联微观结构。通过改变阳离子类型（钙、镁、钠）和浓度，我们系统地调节微凝胶的化学和物理性质，以控制模型化合物的释放速率，包括罗丹明B、亚甲蓝以及各种分子量的葡聚糖。此外，一个聚乙二醇 - 藻酸盐复合微凝胶系统被用于证明罗丹明B的预编程逐步释放。这些发现为具有可控释放性能的离子微凝胶的合成后操作提供了一种直接的策略，为先进的生物医学应用铺平了道路。
