The decrease of tissue
oxygen content due to pathological conditions leads to severe cell death and tissue damage. Restoration of tissue
oxygen content is the primary treatment goal. To accurately and efficiently assess efficacy of a treatment, minimally invasive, and long-term detection of
oxygen concentration in the same tissue location represents a clinically attractive strategy. Among the different
oxygen concentration measurement approaches, electron paramagnetic resonance (EPR) has the potential to accomplish this. Yet there lacks
injectable EPR probes that can maintain a consistent concentration at the same tissue location during treatment period to acquire a stable EPR signal, and can finally be eliminated from body without retrieval. Herein, we developed
injectable and bioeliminable
hydrogel-based polymeric EPR probes that exhibited fast gelation rate, slow
weight loss rate, and high
oxygen sensitivity. The probe was based on
N-Isopropylacrylamide (NIPAAm),
2-hydroxyethyl methacrylate (
HEMA), dimethyl-γ-butyrolactone
acrylate (DBA), and tetrathiatriarylmethyl (TAM) radical. The
injectable probes can be implanted into tissues using a minimally invasive injection approach. The high gelation rate (~10 s) allowed the probes to quickly solidify upon injection to have a high retention in tissues. The polymeric probes overcame the toxicity issue of current small molecule EPR probes. The probes can be gradually hydrolyzed. Upon complete hydrolysis, the probes became water soluble at 37 °C, thus having the potential to be removed from the body by urinary system. The probes showed slow
weight loss rate so as to maintain EPR signal intensity for extended periods while retaining in a certain tissue location. The probes remained their high
oxygen sensitivity after in vitro hydrolysis and in vivo implantation for 4 weeks. These
hydrogel-based EPR probes have attractive properties for in vivo
oxygen detection.