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Transient, resolving inflammation plays a critical role in tissue repair and regeneration. In the context of joint disease, however, chronic inflammation following injury or with osteoarthritis can lead to irreversible articular cartilage degradation and joint pain. Developing tissue engineering strategies for the regeneration of articular cartilage remains challenging due to the harsh inflammatory environment of an injured or arthritic joint, which can promote degradation of engineered tissues as well as native articular cartilage. Here, we developed an artificial gene circuit for controlled, cell-based delivery of biologic drugs, based on a nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-responsive synthetic promoter. Using lentivirus-based gene therapy, we engineered murine induced pluripotent stem cells (iPSCs) capable of attenuating inflammation through controlled release of an anti-inflammatory drug …