02314nas a2200277 4500000000100000000000100001008004100002260001500043653001900058653002000077653001400097653003100111653001600142653001800158100001900176700001700195700002000212700001500232700001700247700001800264245013500282856006700417300001200484520152600496022001402022 2023 d c2023-11-2910acancer-on-chip10acervical cancer10acisplatin10amicrophysiological systems10aneutrophils10aorgan-on-chip1 aElena Kromidas1 aAlicia Geier1 aAdrian Weghofer1 aHui-Yu Liu1 aMartin Weiss1 aPeter Loskill00aImmunocompetent PDMS-Free Organ-on-Chip Model of Cervical Cancer Integrating Patient-Specific Cervical Fibroblasts and Neutrophils uhttps://onlinelibrary.wiley.com/doi/abs/10.1002/adhm.202302714 a23027143 aDespite preventive measures and available treatments, cervical cancer still ranks as the fourth most prevalent cancer among women worldwide and remains the leading cause of cancer death in women in many developing countries. To gain further insights into pathogenesis and to develop novel (immuno)therapies, more sophisticated human models recreating patient heterogeneities and including aspects of the tumor microenvironment are urgently required. A novel polydimethylsiloxane-free microfluidic platform, designed specifically for the generation and ccultivation of cervical cancerous tissue, is introduced. The microscale open-top tissue chambers of the cervical cancer-on-chip (CCoC) enable facile generation and long-term cultivation of SiHa spheroids in co-culture with donor-derived cervical fibroblasts. The resulting 3D tissue emulates physiological architecture and allows dissection of distinct effects of the stromal tissue on cancer viability and growth. Treatment with cisplatin at clinically-relevant routes of administration and dosing highlights the platform's applicability for drug testing. Moreover, the model is amenable for integration and recruitment of donor-derived neutrophils from the microvasculature-like channel into the tissue, all while retaining their ability to produce neutrophil extracellular traps. In the future, the immunocompetent CCoC featuring donor-specific primary cells and tumor spheroids has the potential to contribute to the development of new (immuno)therapeutic options. a2192-2659