Mechanically Tunable Hydrogel Microfibers for Biomimetic Tumor Drug Testing

Abstract Chemotherapy continues to be the principal systemic treatment modality for neuroblastoma patients, yet the absence of accurate in vitro tumor microenvironment models has significantly limited chemotherapeutic efficacy. In this study, innovative bioresponsive hydrogel microfibers is proposed that replicate the mechanical properties of the extracellular matrix surrounding neuroblastoma cells for assessing tumor drug responses. These microfibers feature an alginate/poly (N‐isopropyl acrylamide) shell encapsulating a carboxymethyl cellulose core, fabricated through precision microfluidic technology. Due to the precise manipulation afforded by microfluidics, it is possible to continuously generate fibers that encapsulate cells with uniform dimensions and meticulously defined structures. Additionally, the rapid temperature response characteristics enabled the microfibers to mimic the mechanical properties of the extracellular matrix, thereby regulating the cellular pressure environment and rapidly forming highly active three‐dimensional tumor spheroids. Ultimately, this findings demonstrate that neuroblastoma spheroids within the microfibers display varying sensitivities to different chemotherapy drugs under distinct external pressure conditions. In conclusion, this biomimetic microfiber platform provides a reliable foundation for replicating the neuroblastoma microenvironment and facilitating clinically relevant drug efficacy assessments.