高分子水凝胶因其特殊的三维网络结构和粘弹性能在药物载体等生物材料领域受到很大关注，是当今先进材料研究的热点之一。天然胶原是一种生物高分子，在体外一定溶液条件下能自组装形成水凝胶，但自组装胶原水凝胶的结构性能不稳定，已有研究表明化学交联是最有效的改性途径。针对目前自组装胶原水凝胶化学交联存在的问题，本项目拟依据胶原生物合成的仿生学原理，结合采用胶原自组装和多元羧酸NHS酯调控制备可用作药物载体的胶原水凝胶材料。采用交联度测定、荧光共振能量转移、共聚焦激光显微镜等手段研究溶液中胶原的聚集态结构；采用荧光偏振、二维荧光、流变等手段研究胶原溶液-凝胶相变行为；采用原子力显微镜、动态热机械分析以及对典型抗癌药物的控制释放等手段，研究胶原水凝胶的结构、基本理化性质和载药释药性能；揭示三个方面的关系并获得胶原自组装与多元羧酸NHS酯调控制备药物控释用胶原水凝胶的方法和原理，为胶原基水凝胶材料的制备提供理

Polymeric hydrogel, a hot issue of research in advanced materials, has been given a great attention in the fields of biomaterials including drug delivery since it has special three dimensional network structures and viscoelasticity. Collagen is a biological macromolecule and can self-assemble from solution into a hydrogel under special conditions in vitro. However, the self-assembled collagen hydrogel is structurally unstable and chemical crosslinking has been shown to be the best modification method. Aiming at the problems existed in the chemical crosslinking of self-assembled collagen hydrogel, the fund is to prepare the collagen hydrogel for drug delivery with a combination of collagen self-assembling and multiple carboxylic acidic N-hydroxysuccinimide esters based on the bionics concerning collagen bio- synthesis. The aggregation structure of collagen in solution was studied by the degree of cross-linking determination, fluorescence resonance energy transfer, and confocal reflectance microscopy. The phase change of collagen solution into gel was investigated by fluorescence polarization, two-dimensional fluorescence correlation spectroscopy and rheology. The structure, basic physicochemical properties and the loading-release property of collagen hydrogels were studied by atomic force microscopy, dynamic mechanical analysis, and the controlled release against typical anti-cancer drug. The relationship among these three aspects was accordingly disclosed. The means and principles for the preparation of the collagen hydrogel for drug delivery by collagen self-assembling and multiple carboxylic acidic N-hydroxysuccinimide esters were obtained to supply the preparation of collagen based hydrogels with academic basis.