PURPOSE: Current dry eye treatment includes delivering comfort agents to the eye via drops, but low bioavailability and multiple administration continues to be a barrier to effective treatment. There exists a significant unmet need for devices to treat dry eye and for more comfortable contact lenses. METHODS: Using molecular imprinting strategies with an analysis of biology, we have rationally designed and synthesized hydrogel contact lenses that can release hyaluronic acid (HA) at a controlled rate. RESULTS: Delayed release characteristics were significantly improved through biomimetic imprinting, as multiple functional monomers provided non-covalent complexation points within nelfilcon A gels without altering structural, mechanical, or optical properties. The diffusion coefficient of 1.2 million Dalton HA was controlled by varying the number and variety of functional monomers (increasing the variety lowered the HA diffusion coefficient 1.5 times more than single functional monomers, and 1.6 times more than nelfilcon A alone). CONCLUSIONS: HA can be delivered from a daily disposable lens at a therapeutic rate of approximately 6 microg/h for 24 h. This is the first demonstration of imprinting a large molecular weight polymer within a hydrogel and the effect of imprinting on the reptation of the long chain macromolecule from the structure.