Multiscale Engineering of Cell Scaffold for Bone Regeneration

描述（由申请人提供）：骨植入物在治疗创伤、军事行动、先天性和退行性疾病以及运动和年龄相关伤害的受害者方面需求量很大。对替代组织的需求远远超过了供体组织的可用性。战争造成的伤害进一步加剧了赤字。在这个项目中，我们将针对人工骨植入物的工程设计，这些人工骨植入物可以提供无限的骨材料供应，并消除免疫排斥或疾病转移的风险。借用自然界的概念，我们建议利用多尺度设计的骨支架跨越规模从10-8到10-1米。人工骨组织的多种要求，包括机械和生物学性能，使得这种方法非常必要。将追求以下具体目标，以生产和植入物原型，维持骨细胞的快速发育以及高压缩强度。（一）.制备具有改善的机械性能的PLGA和磷酸钙（CP）纳米颗粒的可生物降解的纳米复合材料（10-8-10-6 μ m规模）;（2）.构建具有倒置胶体晶体（ICC）形貌的3D生物可降解支架结构（10-4-10-6 m尺度）。(3)通过将纳米颗粒应用于支架表面（10-8-10-4 m尺度）优化表面粗糙度来增加细胞附着和生长;（4）.使用计算机设计的横杆几何形状（10-3-10-1 m比例）从PLGA-CP复合材料制备ICC支架;和（5）。具有最佳几何形状、机械性能和表面粗糙度的集成支架的体内测试。这些特定目标将使我们能够获得可植入支架的原型，识别潜在的挑战，并证明或反驳人工骨多尺度设计的主要概念。

DESCRIPTION (provided by applicant): Bone implants are in great demand for the treatment of for victims of trauma, military actions, congenital and degenerative diseases, as well as sports- and age-related injuries. The need for replacement tissue far outweighs the availability of donor tissue. The deficit is further exacerbated by war injuries. In this project we will target engineering of artificial bone implants that can potentially provide an endless supply of the bone material and eliminate the risk of immune rejection or disease transfer. Borrowing the concept from Nature, we propose to take advantage of multi-scale design of the bone scaffolds spanning the scale from 10-8 to 10-1 m. Multiple requirements of the artificial bone tissue, that include both mechanical and biological properties, make this approach acutely necessary. The following Specific Aims will be pursued to produce and implant prototype sustaining rapid development of bone cells, as well as high compression strengths. (1). Preparation of a biodegradable nanocomposite of PLGA and calcium phosphate (CP) nanoparticles with improved mechanical properties (10-8-10-6 m scale); (2). Construction of 3D biodegradable scaffold structure with inverted colloidal crystal (ICC) topography (10-4-10-6 m scale). (3) Increased cell attachment and growth by optimizing surface roughness through the application of nanoparticles to the scaffold surface (10-8-10-4 m scale); (4). Preparation of ICC scaffolds from PLGA-CP composite with a computer-designed cross-bar geometry (10-3-10-1 m scale); and (5). In vivo testing of the integrated scaffold with optimal geometry, mechanical properties, and surface roughness. These Specific Aims will allow us to obtain prototypes of implantable scaffolds, identify potential challenges and prove or disprove the principal concept of multi-scale design for artificial bone.