Self-Assembly of Mesostructure Biomaterials

描述（由申请人提供）：这项为期两年的提案研究了使用自组装合成具有多孔三维（3D）结构的生物材料的可行性。许多设想的生物医学装置的开发，包括用于组织修复的支架和支架、用于离体细胞扩增的生物反应器和用于受控药物递送的微粒，将需要精确控制生物材料的孔径和几何形状的方法。目前的3D制造方法通常依赖于机械加工或逐层光刻，因此在速度、分辨率或对软材料的适用性方面受到限制。为了解决这些限制，所提出的工作使用微尺度液体膜之间的定向选择力来实现3D结构的组装。这种广泛适用的材料合成策略提供了在1至1000微米尺寸尺度下对孔径和几何形状的控制，从而能够合成具有复杂内部结构的生物材料。具体而言，这项工作将针对适合作为生物反应器的材料的组装，该生物反应器可以在整个工程组织构建体中运输和交换气体或溶液。这些自组装材料将具有大的表面积与体积比和宽度为10-50微米的内部通道网格。自组装过程将依赖于10至100微米大小的金属多面体之间的毛细作用力，以诱导多面体聚集成多孔支架。在惰性金属、可降解聚合物和I型胶原凝胶中复制这些开放几何形状将产生具有一组用于内部灌注的通道的模型组织构造。这项工作将创建三种类型的生物反应器：（1）具有有序阵列的互连通道的胶原蛋白凝胶，（2）其通道由金属支持物内衬的多孔胶原蛋白凝胶，以及（3）其通道由人脐静脉内皮细胞内衬的多孔胶原蛋白凝胶。每个反应器将由包埋在凝胶中的人真皮成纤维细胞组成;对于每种类型的反应器，这项工作将确定网络几何形状和灌注速率如何影响成纤维细胞的最大可持续密度及其增殖和凋亡速率。

DESCRIPTION (provided by applicant): This two-year proposal examines the feasibility of using self-assembly to synthesize biomaterials that have porous three-dimensional (3D) architectures. Development of many envisioned biomedical devices, including scaffolds and stents for tissue repair, bioreactors for the expansion of cells ex vivo, and microparticles for controlled drug delivery, will require methods to precisely control the pore sizes and geometries of biomaterials. Current methods for 3D fabrication often rely on machining or layer-by-layer lithography, and are thus limited in speed, resolution, or applicability to soft materials. To address these limitations, the proposed work uses directional, selective forces between microscale liquid films to effect assembly of 3D structures. This broadly applicable strategy for materials synthesis affords control over pore sizes and geometries at the 1- to 1000-micrometer size scale, and thereby enables the synthesis of biomaterials that have complex internal structure. Specifically, this work will target the assembly of materials suitable as bioreactors that can transport and exchange gases or solutions throughout an engineered tissue construct. These self-assembled materials will have large surface area-to-volume ratios and a grid of internal channels 10-50 micrometers in width. The self-assembling process will rely on capillary forces between 10- to 100-micrometer-sized metallic polyhedra to induce the aggregation of polyhedra into porous scaffolds. Replication of these open geometries in inert metals, degradable polymers, and type I collagen gels will yield model tissue constructs that possess a set of channels for internal perfusion. This work will create three types of bioreactors: (1) collagen gels that have ordered arrays of interconnected channels, (2) porous collagen gels whose channels are lined by a metallic support, and (3) porous collagen gels whose channels are lined by human umbilical vein endothelial cells. Each reactor will consist of human dermal fibroblasts embedded within a gel; for each type of reactor, this work will determine how network geometry and perfusion rate affect the maximum sustainable density of fibroblasts and their rates of proliferation and apoptosis.