Dynamically Crosslinked Hydrogels

描述（由申请方提供）：提出了对三磷酸腺苷（ATP）有响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。这些互穿网络将通过ATP依赖的驱动蛋白马达蛋白而活跃地交联。据预测，水凝胶在ATP存在下会迅速而有力地收缩，就像合成肌肉一样。建议的具体目标是：（一）为了通过用HPMA聚合物刷修饰微管来稳定微管在整个pHPMA基质中的分散，ii.）通过将重组驱动蛋白马达通过其货物结合端与pHPMA偶联，交联微管和pHPMA基质。与活性驱动蛋白交联的水凝胶的物理性质将关于凝胶组成和交联密度来表征，iii.）表征水凝胶的ATP响应性。将测定药物（多柔比星）响应ATP的卸载速率和程度。这些新型水凝胶在药物输送、活性表面涂层或医疗器械中的微致动器等方面具有广泛的生物医学应用前景。

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.