Mechanochemical Reaction Cascade for Sensitive Detection of Covalent Bond Breakage in Hydrogels

A novel strategy is reported for sensing chemical bond breakage in hydrogels at low levels of mechanical stress using a mechanochemical reaction cascade to generate fluorescence. Hydrogels are promising substrates and frameworks for cell growth and tissue engineering, particularly for cardiovascular repair and cartilage replacement. For these applications, it is important to maintain careful control over gel mechanical properties so that these hydrogels not only match the properties of the desired tissue for replacement but also retain their integrity for extended periods. Since the failure of hydrogels begins with the breakage of cross-links within the structure, methods are needed to sense these initial events for monitoring the performance of implants. In this work, it was hypothesized that nonspecific covalent bond breakage would produce radicals that would react with water to produce reactive oxygen species, which in turn could activate fluorophores sensitive to these. A series of multiarm poly(ethylene glycol) hydrogels were synthesized with a variety of cross-links of different bond dissociation energies. It was found that gels loaded with the masked fluorophore 3'-(p-aminophenyl) fluorescein became fluorescent during compression, even with as little as 5 kPa of pressure. The effect of compression on fluorescence activation was found to depend primarily on the strength of the cross-linking functional group. Future studies include utilizing this system to image mechanical variability in heterogeneous gel structures.