Development of long-term implantable luminescent biosensors for subcutaneous oxygen has proved challenging due to difficulties in immobilizing a biocompatible matrix that prevents sensor aggregation yet maintains sufficient concentration for transdermal optical detection. Here, Pd-porphyrins can be used as PEG cross-linkers to generate a polyamide hydrogel with extreme porphyrin density (≈5 × 10−3m). Dye aggregation is avoided due to the spatially constraining 3D mesh formed by the porphyrins themselves. The hydrogel exhibits oxygen-responsive phosphorescence and can be stably implanted subcutaneously in mice for weeks without degradation, bleaching, or host rejection. To further facilitate oxygen detection using steady-state techniques, an oxygen-non-responsive companion hydrogel is developed by blending copper and free base porphyrins to yield intensity-matched luminescence for ratiometric detection.Pd-porphyrins
are used as cross-linkers to generate an oxygen-responsive polyamide hydrogel. The implantable hydrogel is stable in vivo for weeks, biocompatible, and the high density of the Pd-porphyrin enables transdermal detection. By changing Pd chelation for Cu and free base porphyrins, an intensity-matched companion hydrogel is developed for a ratiometric sensing strategy.