Permeable Hydrogel Encapsulated Osteosarcoma-on-a-Chip for High-Throughput Multi-Drugs Screening

Pharmacological chemotherapy remains a cornerstone in treating osteosarcoma (OS), where the application of drug combinations not only enhances therapeutic efficacy but also mitigates adverse side effects. However, the absence of an efficient and reliable drug screening platform poses a significant challenge in optimizing these combination therapies. In this study, we introduce a novel OS chip designed to facilitate the high-throughput and precise evaluation of drug combination efficacy, addressing this critical gap in OS treatment research. Leveraging the precise control of microfluidic electrospray technology, we successfully fabricated core–shell microcarriers (CSMs) encapsulating OS cells with uniform size and monodisperse distribution. Through three-dimensional culture, OS cell spheroids were efficiently formed within the CSMs, which were subsequently integrated into a microfluidic chip equipped with a concentration gradient generator and cell culture chambers. This innovative platform enables high-throughput screening of single drugs and diverse drug combinations. Our results demonstrate that this OS-on-a-chip exhibits significant potential for clinical drug screening, offering a robust tool for optimizing therapeutic strategies in OS treatment. Summary Innovative osteosarcoma-on-a-chip for high-throughput drug screening Core–shell microcarriers enable uniform 3D OS spheroid formation Microfluidic electrospray technology for precise drug combination testing Concentration gradient generator enhances multi-drug efficacy evaluation