Granular Hydrogel Composites for Noninvasive Optical Biosensing

Granular hydrogels are attracting increasing attention for tissue engineering and regenerative medicine applications, owing to their highly tunable physical characteristics, exceptional modularity, and naturally interconnected microporosity. These features are also attractive for next-generation biosensors that better integrate with the body. To apply the granular hydrogel paradigm to biosensor development, porphyrin-containing chemo-optical oxygen- and glucose-biosensing microdomains were encapsulated within poly(ethylene glycol) (PEG) hydrogel microparticles (80.8 ± 37.0 μm), which were fabricated using thiol-vinyl sulfone chemistry and a batch emulsification. Importantly, the granular hydrogel system demonstrated shear thinning capabilities and were annealed with a PEG-tetra-thiol linker to form granular hydrogels. This granular hydrogel platform possessed an average porosity of 25.0% ± 6.6% and a low shear storage modulus of 1448.7 ± 708.3 Pa, indicating a low crosslinking density and large mesh size, which permits analyte diffusion to the sensing microdomains. In vitro testing of granular hydrogels loaded with oxygen-biosensing microdomains demonstrated responsiveness from 0% to 21% oxygen and a Stern-Volmer quenching constant of 0.0131 ± 0.0003 μM^-1. Additionally, in vitro testing of granular hydrogels with glucose-biosensing microdomains under a physiologically relevant oxygen concentration demonstrated a glucose sensitivity of 0.308 ± 0.068 μs·dL/mg, and a sensing range of detection from 32.8 ± 18.0 to 180.9 ± 17.8 mg/dL, which spans from hypoglycemia to mild hyperglycemia. Furthermore, biosensing performance was maintained after electron-beam sterilization. In summary, these results demonstrate proof-of-concept for integrating chemo-optical biosensors into granular hydrogels as well as the ability to measure physiologically relevant fluctuations in oxygen and glucose.