Rapid Fabrication of Diverse Hydrogel Microspheres for Drug Evaluation on a Rotating Microfluidic System

Abstract

Hydrogel microspheres are considered ideal carriers with broad applications in 3D cell culture, drug delivery, and microtissue construction. Although multiple methods have been developed for generating hydrogel microspheres, there is still a lack of a universal approach that combines operability, stability, cost-effectiveness, and biocompatibility. In this work, a novel rotating microfluidic system (RMS) is proposed, which can rapidly fabricate diverse poly(ethylene glycol) diacrylate/sodium alginate (PEGDA/SA) hydrogel microspheres by motor-driven rotation of the oil phase to form a special T-shaped structure with the needle. The main part of the system consists of commercially available motors, a beaker, and needles that do not require precision machining and are user-friendly with low cost. Moreover, by adjusting system parameters such as the needle structure, flow rate, and rotational speed, the platform enables rapid fabrication of hydrogel microspheres with different sizes and diverse cores, including crescent, thick wavy, oval, and spherical. Furthermore, tumor cell-laden hyaluronic acid methacrylate/sodium alginate (HAMA/SA) hydrogel microspheres were fabricated by using this system, which demonstrated good cell viability and proliferation in the subsequent 3D culture. In vitro drug evaluation of tumor models using cisplatin revealed the potential of this system for drug evaluation. These results indicated that RMS has good potential in other 3D cell culture-based biomedical applications.