Living Biohybrid Hydrogels for Co‐Delivery of Oxygen, Anti‐Cancer Drugs, and Probiotics: Effects on Cancer and Healthy Cell Viability

In recent studies, oxygen (O 2 ) delivery biomaterials have been developed to reduce hypoxia‐induced problems in, e.g., tumor tissues. However, none of these studies have used inhibitory effects of probiotics in combination therapies with O 2 and anticancer drugs for advanced cancer treatment applications. In this study, we report a new probiotic‐enriched 3D‐printed biomaterial (3D‐BioHybrid‐DOX/SPEP) that is capable of O 2 , probiotic, and acidic pH (pH 6.0) sensitive anticancer drug (Doxorubicin = DOX) co‐release. 3D‐BioHybrid‐DOX/SPEP shows sustained O 2 and pH‐responsive anticancer drug release over 14 days. The release of short‐chain fatty acids, including butyric acid, was detected on days 1 and 7 of incubation, indicating that the O 2 delivery component of the system supports probiotic viability while mitigating the toxic effects of DOX. The CFU results show that the 3D‐BioHybrid‐DOX/SPEP supports probiotic viability at 1 and 7 days of incubation. In vitro cell experiments indicate that the healthy cell viability is ca. 2 times higher than cancer cells after 1 and 7 days of incubation at hypoxia conditions in 3D‐BioHybrid‐DOX/SPEP due to the co‐administration of O 2 , DOX, and probiotics.