Abstract Chronic wounds and fibrotic scarring represent a significant unmet clinical need, affecting millions of patients annually and resulting in impaired tissue function, pain, and reduced quality of life. Current therapeutic approaches lack the spatiotemporal precision needed to modulate the wound microenvironment dynamically, devoid of delivering anti-inflammatory signals early and anti-fibrotic signals later in response to the wound’s own molecular cues. This project proposes the design and experimental validation of a two-stage, NF-κB/STAT3-responsive synthetic gene circuit encoded in a piggyBac transposon vector, engineered for stable integration into dermal fibroblasts. The circuit is designed to first sense early inflammatory NF-κB signaling and secrete IL-10 (an anti-inflammatory cytokine), then switch to a STAT3/NF-κB dual-input logic gate that drives decorin secretion (an anti-fibrotic proteoglycan) as the wound transitions to the proliferative phase. A dual Bxb1 serine integrase and PhiC31 integrase-based irreversible switching mechanism ensures the circuit can irreversibly switch off each phase sequentially, preventing vulnerability to infection or inability to properly heal. mCherry (Stage 1) and EGFP (Stage 2) have been incorporated to enable real-time monitoring of circuit state for testing circuit function and logic. Ideally, this genetic circuit would be transfected in patient-derived fibroblasts, which would be seeded into sutures used at the wound edge.