Inorganic-Organic Interpenetrating Network Hydrogels as Tissue-Integrating Luminescent Implants: Physicochemical Characterization and Preclinical Evaluation

Sensors capable of accurate, continuous monitoring of biochemistry are crucial to the realization of personalized medicine on a large scale. Great strides have been made to enhance tissue compatibility of long-term in vivo biosensors using biomaterials strategies such as tissue-integrating hydrogels. However, the low level of oxygen in tissue presents a challenge for implanted devices, especially when the biosensing function relies on oxygen as a measure-either as a primary analyte or as an indirect marker to transduce levels of other biomolecules. This work presents a method of fabricating inorganic-organic interpenetrating network (IPN) hydrogels to optimize the oxygen transport through injectable biosensors. Capitalizing on the synergy between the two networks, various physicochemical properties (e.g., swelling, glass transition temperature, and mechanical properties) are shown to be independently adjustable while maintaining a 250% increase in oxygen permeability relative to poly(2-hydroxyethyl methacrylate) controls. Finally, these gels, when functionalized with a Pd(II) benzoporphyrin phosphor, track tissue oxygen in real time for 76 days as subcutaneous implants in a porcine model while promoting tissue ingrowth and minimizing fibrosis around the implant. These findings support IPN networks for fine-tuned design of implantable biomaterials in personalized medicine and other biomedical applications.

Automated summary

The fabrication of inorganic-organic interpenetrating network (IPN) hydrogels offers an optimized oxygen transport system for injectable biosensors, with independently adjustable physicochemical properties while maintaining a 250% increase in oxygen permeability compared to controls. The functionalized gels, equipped with Pd(II) benzoporphyrin phosphor, successfully tracked tissue oxygen levels for 76 days in a subcutaneous porcine model, promoting tissue ingrowth and minimizing fibrosis around the implant. These findings demonstrate the potential of IPN networks for tailored design of implantable biomaterials in personalized medicine and other biomedical applications.