THERMAL ASSEMBLY OF MINERAL/COLLAGEN BIOMATERIALS

可注射的生物材料在原位经历从液体到固体或半固体的转变，在许多颅面和牙科外科手术中作为重建和治疗材料具有潜在的用途。仿生策略是设计新的重建生物材料，可以从矿化组织形成过程中发生的潜在生化和生物物理过程中得到启发。本研究的长期目标是采用原位自组装的生物启发策略来形成胶原-矿物复合生物材料。最近，我们已经证明合成磷脂囊泡（脂质体）的隔室可以用来控制磷酸钙溶液中的矿物形成。我们设计的脂质体可以在室温下隔离钙，但在加热到体温时迅速释放钙。由载钙脂质体组成的高度过饱和溶液悬浮在磷酸钠水溶液中，发现在环境条件下不反应，但当加热到体温时迅速形成磷酸钙矿物。在这项研究中，我们将利用环境温度和体温之间的差异来触发复合生物材料的原位形成。我们的一般假设是，1型胶原的热触发脂质体矿化和热凝胶化的双重过程可以被利用来形成具有有用临床性能的自组装胶原/矿物复合生物材料。以下具体目标旨在验证这些假设，并确定这些生物材料的结构-性质关系：1)制备含磷酸盐脂质体，并研究其与载钙脂质体结合使用以热触发形成磷酸钙矿物。2)将脂质体介导的热矿化与I型胶原的热凝胶化相结合，制备原位成型的胶原/矿物仿生复合材料。3)利用扫描电镜和透射电镜测定胶原网络结构和矿物-胶原相互作用对复合性能的影响。4)利用动态力学分析来确定矿物质含量、胶原蛋白结构以及矿物质-胶原蛋白相互作用对机械强度的影响。

Injectable biomaterials which undergo a transformation from a fluid to a solid or semi-solid in-situ are potentially useful as reconstructive and therapeutic materials in numerous craniofacial and dental surgical procedures. Biomimetic strategies are designing new reconstructive biomaterials can be inspired by the underling biochemical and biophysical processes which occur during mineralized tissue formation. The long term goal of this research is to employ the bioinspired strategy of in-situ self-assembly to form a collagen-mineral composite biomaterial. Recently, we have shown that the compartments of synthetic phospholipid vesicles (liposomes) can be exploited to control mineral formation in a calcium phosphate solution. We designed liposomes which sequestered Ca at room temperature but released Ca rapidly when heated to body temperature. Highly supersaturated solutions consisting of Ca loaded liposomes suspended in aqueous sodium phosphate were found to be unreactive under ambient conditions, but rapidly formed calcium phosphate minerals when heated to body temperature. In this research we will exploit the difference between ambient and body temperature to trigger in-situ formation of a composite biomaterial. Our general hypothesis is that the dual processes of thermally triggered liposomal mineralization and thermal gelation of type 1 collagen can be exploited to form a self-assembling collagen/mineral composite biomaterial with useful clinical properties. The following specific aims are designed to test these hypotheses, and to determine the structure-property relationships of these biomaterials: 1) Prepare phosphate-containing liposomes and study their use in combination with calcium-loaded liposomes for thermally-triggered formation of calcium phosphate minerals. 2) Combined liposome-mediated thermal mineralization with thermal gelation of type I collagen to create an in-situ forming collagen/mineral biomimetic composite. 3) Utilize scanning and transmission electron microscopy to determine collagen network structure and mineral-collagen interactions on composite properties. 4) Utilize dynamic mechanical analysis to determine the effect of mineral content, collagen structure, and mineral-collagen interactions on mechanical strength.