Post-fabrication reconfiguration of hydrogels through thermodynamic asymmetry in dynamic chemistry

Designing soft materials with adaptive properties requires internal chemical processes that enable reconfiguration across multiple system levels. Dynamic covalent chemistry has provided powerful routes to dynamic polymer networks, yet it is typically employed in an equilibrium-based manner where the identity of the dynamic bond remains unchanged. Here, we introduce thermodynamic asymmetry in dynamic covalent chemistry to enable the replacement of network-defining linkages after material formation, rather than their mere bond shuffling. For combinations of hydrazones and oximes, we demonstrate near-quantitative hydrazone-to-oxime exchange under aqueous conditions. Kinetic modeling elucidates that the exchange is dominated by a hydrolytic pathway with a non-trivial concentration dependence. This chemistry enables diverse reconfigurations within hydrogels after their initial synthesis, achieving near-complete replacement at material scale. Treating pre-formed hydrazone gels with functional alkoxyamines enables topological, mechanical, and functional reprogramming without network deconstruction. This work establishes thermodynamically biased dynamic covalent exchange as a generalizable principle for materials, surface functions, or self-assembling systems, illustrating how molecular reaction pathways can be harnessed to deterministically alter structural and functional identity.