Optimizing Mandibular Scaffold Modulus/Porosity Balance

描述（由申请人提供）：虽然骨组织工程理想地基于从支架功能到共享骨/支架功能到完全天然骨的过渡，但几乎没有关于设计支架来优化这种过渡的信息。一个简单的出发点是将支架功能与力学模量和组织再生与支架孔隙率/渗透性联系起来。基本的支架设计问题变成了“在模量和相互连接的孔隙率/渗透性之间的正确平衡是什么，以便支架能够承受载荷，直到再生组织能够承受载荷？”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关系的支架结构，用骨工程材料制造这些复杂的支架，并在具有良好特征的体内承重模型中测试这些支架。

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.