Optimizing Mandibular Scaffold Modulus/Porosity Balance

优化下颌支架模量/孔隙率平衡

• 批准号: 7117770
• 负责人: Scott J Hollister
• 金额: $ 54.47万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7117770
• 关键词: bioengineering /biomedical engineering; biomaterial development /preparation; biomaterial evaluation; biomaterial interface interaction; biomechanics; biotechnology; bone regeneration; computed axial tomography; mandibular condyle; membrane permeability; miniature swine; statistics /biometry; tissue engineering; tissue support frame

DESCRIPTION (provided by applicant): While skeletal tissue engineering is ideally based on transition from scaffold function to shared bone/scaffold function to completely natural bone, almost no information exists on designing scaffolds to optimize this transition. A simplified starting point is to associate scaffold function with mechanical modulus and tissue regeneration with scaffold porosity/permeability. The fundamental scaffold design question becomes "What is the right balance between modulus and interconnected porosity/permeability such that the scaffold can bear load until the regenerate tissue can bear load?". To answer this critical question we must be able to design scaffold architectures with specific modulus porosity relationships, fabricate these complex scaffolds from bone engineering materials, and test these scaffolds in a well characterized in vivo load bearing model. Our global hypothesis is that a minimally stiff scaffold (stiff equates to modulus) capable of load bearing coupled with the highest interconnected porosity/permeability will achieve optimal bone regeneration. Our goal is to define "minimally stiff' and "highest porosity/permeability" in an in vivo functional load bearing site. We will test this hypothesis through the following three specific aims: Specific Aim 1. Use computational topology optimization techniques to design scaffold architectures with four modulus/porosity ratios that span the theoretical Hashin-Shtrikman bounds initially and after degradation. Specific Aim 2. Fabricate designed scaffold architectures from PPF/TCP using Solid Free-Form Fabrication techniques. Micro-CT scaffolds to examine architecture and measure scaffold permeability. Specific Aim 3.Test scaffolds in minipig mandibular condyle load bearing site that has known bone regeneration dynamics. Determine how modulus/porosity ratios correlate with bone regeneration at 4 and 8 weeks using 3D quantitative micro-CT, mechanical testing, and histology. The results will provide quantitative information as to what modulus is necessary for load bearing and how designed porosity/permeability influence bone regeneration. This information will provide guidelines for designing scaffolds to optimize transition from scaffold load bearing to bone regeneration and load bearing.

描述（由申请人提供）：虽然骨骼组织工程理想地基于从支架功能到共享骨/支架功能再到完全天然骨的转变，但几乎不存在关于设计支架以优化这种转变的信息。一个简化的起点是将支架功能与机械模量相关联，将组织再生与支架孔隙率/渗透性相关联。基本的支架设计问题变成“模量和互连孔隙率/渗透性之间的正确平衡是什么，使得支架可以承受负载，直到再生组织可以承受负载？”。为了回答这个关键问题，我们必须能够设计具有特定模量孔隙率关系的支架结构，用骨工程材料制造这些复杂的支架，并在特征良好的体内承载模型中测试这些支架。 我们的总体假设是，能够承载的最小刚性支架（刚性等于模量）与最高的互连孔隙率/渗透性相结合将实现最佳的骨再生。我们的目标是定义体内功能性承载部位的“最小刚性”和“最高孔隙度/渗透性”。我们将通过以下三个具体目标来检验这一假设： 具体目标 1. 使用计算拓扑优化技术来设计具有四种模量/孔隙率比的支架结构，这些比值跨越初始和降解后的理论 Hashin-Shtrikman 边界。 具体目标 2. 使用固体自由成型制造技术从 PPF/TCP 制造设计的脚手架架构。 Micro-CT 支架用于检查结构并测量支架渗透性。 具体目标 3. 在已知骨再生动力学的小型猪下颌骨髁承载部位测试支架。使用 3D 定量显微 CT、机械测试和组织学确定模量/孔隙率比与 4 周和 8 周时骨再生的关系。结果将提供关于承载所需的模量以及设计的孔隙率/渗透性如何影响骨再生的定量信息。该信息将为设计支架提供指导，以优化从支架承载到骨再生和承载的过渡。