Hybrid Inorganic-Organic Interpenetrating Network Hydrogels as Optical Biosensors

Chronic disease management currently requires frequent withdrawal of bodily fluids to assess biomolecule levels and are associated with patient discomfort and noncompliance. Thus, a need exists for less invasive, on-demand biochemistry monitoring. Our lab has investigated poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogels functionalized with glucose oxidase and palladium benzoporphyrin phosphors as fully-implantable luminescent glucose sensors. These pHEMA-based sensors can be injected subcutaneously and have successfully monitored rising and falling blood glucose two hours after implantation in porcine models. However, decreasing tissue oxygen levels near the sensor as the injection site heals prevented long-term sensor function in vivo (i.e. 30 days). This work investigates the use of the siloxane methacrylate, 3-[Tris(trimethylsiloxy) silyl]propyl methacrylate (TRIS) and N, N-dimethyl acrylamide (DMA) to create hybrid inorganic-organic interpenetrating network hydrogels (IPNs). IPNs were fabricated using a sequential polymerization method. A 50:50 v:v% TRIS:DMA hydrogel containing a palladium benzoporphyrin oxygen indicator was fabricated. This first network was then soaked overnight in a DMA homopolymer precursor, photopolymerized throughout the first network, and hydrated in PBS. Stern-Volmer oxygen diffusion kinetics (luminescence lifetime) indicate a 300% increase in oxygen permeability through the IPNs compared to pHEMA. Additionally, we have enhanced gel hydration by 33% while maintaining similar glucose transport to pHEMA gels (Dglucose = 3.6 x 10-7cm2/s). Introduction of microdomains containing glucose oxidase indicate optical response to glucose in the hypo-and euglycemic ranges in vitro, indicating potential of these gels as glucose biosensors. Ongoing efforts include extending the dynamic range into the hyperglycemic region and evaluating in vivo performance of IPNs as oxygen sensors (phosphor only) and glucose sensors (IPN microcomposite) in porcine models.