Abstract
Endometriosis (EMs), a significant global health issue, characterized by unclear pathogenesis, nonspecific symptoms, and poor treatment outcomes. The organ-on-chip technology has achieved great advances in disease modeling, yet its potential in EMs-related research remains largely untapped. Herein, a microfluidic chip platform that integrates primary cell-laden microcapsules for personalized drug evaluation. Specifically, primary human ectopic endometrial stromal cells (hESCs) within microcapsules featuring a biocompatible carboxymethyl cellulose (CMC) core and a stable alginate (ALG) shell using precise microfluidic electrospray are encapsulated. These microcapsules are integrated into a chip with a branched gradient generator and multiple cell-culture chambers, enabling tailored and high-throughput drug screening. By exposing hESCs-microcapsules derived from primary cells of distinct patient individuals to various drugs on-chip, significant inter-individual variability was revealed, with a strong correlation to clinical outcomes. This unique combination of patient-specific 3D microenvironments and dynamic drug gradient control represents a paradigm shift in personalized EMs research. Further integrating with omics techniques, its capability in exploring promising drugs is showcased. These results reveal that the chip platform could deliver dependable and personalized drug screening outcomes, thereby benefiting both scientific inquiries and clinical therapies.