Multiscale Engineering of Cell Scaffold for Bone Regeneration

骨再生细胞支架的多尺度工程

• 批准号: 7248101
• 负责人: Nicholas Alexander Kotov
• 金额: $ 32.66万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7248101
• 关键词: Adhesions; Affect; Animal Testing; Animals; Architecture; Biological; Bone Marrow; Bone Regeneration; Bone Tissue; Bone Transplantation; Caliber; Cell Adhesion; Cell Density; Cell-Matrix Junction; Chemistry; Coculture Techniques; Condition; Controlled Environment; Cultured Cells; Defect; Degenerative Disorder; Development; Diffusion; Disease; Elasticity; Engineering; Facility Construction Funding Category; Goals; Growth; Hydroxyapatites; Immune; Implant; Infection; Injury; Life; Mechanics; Methods; Military Personnel; Modification; Molds; Morphology; Natural regeneration; Nature; Nutrient; Operative Surgical Procedures; Osteoblasts; Performance; Polymers; Porosity; Predisposition; Preparation; Process; Property; Range; Rate; Research; Research Personnel; Risk; SCID Mice; Shapes; Solutions; Sports; Stromal Cells; Structure; Surface; Surface Properties; Techniques; Testing; Tissue Donors; Tissue Engineering; Tissues; Trauma; War; Weight-Bearing state; age related; allogenic bone transplantation; base; bone; bone cell; calcium phosphate; calcium phosphate coating; cell growth; cell motility; cellular engineering; computer design; concept; design; desire; implantation; improved; in vivo; migration; nanocomposite; nanoparticle; nanoscale; nanostructured; polylactic acid-polyglycolic acid copolymer; programs; prototype; scaffold; subcutaneous; tissue regeneration

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.

描述（由申请人提供）：骨植入物在创伤、军事行动、先天性和退行性疾病以及运动和年龄相关损伤的受害者的治疗中需求量很大。对替代组织的需求远远超过供体组织的可用性。战争造成的伤害进一步加剧了赤字。在这个项目中，我们的目标是人造骨植入物的工程，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。借用大自然的概念，我们建议利用骨支架的多尺度设计，从10-8米到10-1米不等。人工骨组织的多种要求，包括机械和生物特性，使得这种方法非常必要。以下具体目标将追求生产和植入维持骨细胞快速发育的原型，以及高压缩强度。（1). 具有良好力学性能的可降解聚乳酸-磷酸钙纳米复合材料的制备（10-8-10-6 m尺度）（2). 构建具有倒胶体晶体（ICC）形貌的三维可生物降解支架结构（10-4-10-6 m尺度）。(3)通过在支架表面应用纳米颗粒优化表面粗糙度，增加细胞附着和生长（10-8-10-4 m尺度）；(4)。计算机设计交叉杆结构（10-3-10-1 m）的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。这些具体目标将使我们能够获得可植入支架的原型，确定潜在的挑战，并证明或反驳人工骨多尺度设计的主要概念。