THERMAL ASSEMBLY OF MINERAL/COLLAGEN BIOMATERIALS

可注射生物材料可在体内从液体转化为固体或半固体，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应用前景。仿生策略是设计新的重建生物材料，可以受到矿化组织形成过程中潜在的生化和生物物理过程的启发。这项研究的长期目标是利用生物启发的原位自组装策略来形成胶原-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)的隔室可以被用来控制钙磷酸盐溶液中的矿物形成。我们设计了在室温下隔离钙，但加热到体温时迅速释放钙的脂质体。载钙脂质体悬浮在磷酸钠水溶液中的高过饱和溶液在环境条件下不发生反应，但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人体温度之间的差异来触发原位形成复合生物材料。我们的一般假设是，利用热触发的脂质体矿化和1型胶原的热凝胶化的双重过程，可以形成具有临床应用价值的自组装胶原/矿物复合生物材料。为了验证这些假说，并确定这些生物材料的结构-性能关系，我们设计了以下特定目标：1)制备含磷脂质体，并研究其与载钙脂质体在热触发下形成磷酸钙矿物的联合使用。2)将脂质体介导的热矿化与I型胶原的热凝胶化相结合，形成原位形成的胶原/矿物仿生复合材料。3)利用扫描和透射电子显微镜确定胶原网络结构和矿物质-胶原相互作用对复合材料性能的影响。4)利用动态力学分析来确定矿物含量、胶原结构以及矿物-胶原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.