Dynamically Crosslinked Hydrogels

描述（由申请人提供）：提出对三磷酸腺苷（ATP）有反应的动态交联水凝胶。水凝胶将由HPMA [N-（2-羟丙基）甲基丙烯酰胺]共聚物和微管细丝的互穿网络组成。互穿网络将通过atp依赖的运动蛋白主动交联。预计水凝胶在ATP的存在下会迅速而有力地收缩，就像合成肌肉一样。该建议的具体目标是：1)通过用HPMA聚合物刷修饰微管来稳定微管在pHPMA基质中的分散。通过重组激酶马达的载货结合端与pHPMA偶联，将微管与pHPMA基质交联。与活性激酶交联的水凝胶的物理性质将与凝胶组成和交联密度有关。表征水凝胶对ATP的响应性。药物（阿霉素）对ATP反应的卸载速率和程度将被确定。这些新型水凝胶可以在药物输送中找到广泛的生物医学应用，作为医疗设备中的活性表面涂层或微致动器。

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.