Dynamically Crosslinked Hydrogels

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DESCRIPTION (provided by applicant): Dynamically crosslinked hydrogels that respond to adenosine triphosphate (ATP) are proposed. The hydrogels will consist of interpenetrating networks of HPMA [N-(2-hydroxypropyl)methacrylamide] copolymers and microtubule filaments. The interpenetrating networks will be actively crosslinked through ATP-dependent kinesin motor proteins. The hydrogels are predicted to contract rapidly and forcefully in the presence of ATP, like a synthetic muscle. The specific aims of the proposal are: i.) To stabilize the dispersion of microtubules throughout a pHPMA matrix by modifying microtubules with HPMA polymer brushes, ii.) To crosslink microtubules and a pHPMA matrix by conjugating recombinant kinesin motors through their cargo-binding end to pHPMA. The physical properties of hydrogels crosslinked with active kinesin will be characterized in relation to the gel composition and crosslinking density, iii.) To characterize the ATP responsiveness of the hydrogels. The rate and extent of unloading of a drug (doxorubicin) in response to ATP will be determined. These novel hydrogels may find wide ranging biomedical applications in drug delivery, as active surface coatings or microactuators in medical devices.