Optimizing Mandibular Scaffold Modulus/Porosity Balance

描述(申请人提供)：虽然骨组织工程的理想基础是从支架功能到共享骨/支架功能再到完全自然的骨的过渡，但几乎没有关于设计支架来优化这种过渡的信息。一个简化的起点是将支架功能与机械弹性系数相关联，并将组织再生与支架孔隙率/渗透率相关联。支架设计的基本问题变成了“在弹性系数和相互连接的孔隙率/渗透率之间达到什么样的平衡，才能使支架能够承受负荷，直到再生组织能够承受负荷？”为了回答这个关键问题，我们必须能够设计具有特定模孔率关系的支架结构，用骨工程材料制造这些复杂支架，并在具有良好特性的活体承载模型中测试这些支架。 我们的总体假设是，能够承载负荷的最小硬度支架(刚性等于弹性系数)，再加上最高的相互连接的孔隙率/渗透率，将实现最佳的骨再生。我们的目标是定义体内功能承重部位的“最小硬度”和“最高孔隙率/渗透率”。我们将通过以下三个具体目标来验证这一假设： 具体目标1.使用计算拓扑优化技术设计具有四个模孔率的脚手架结构，其初始和退化后均跨越理论Hashin-Shtrikman界限。 具体目标2.利用固体自由成型技术制作PPF/TCP设计的脚手架结构。Micro-CT支架用于检查建筑和测量支架的渗透性。 具体目的3.在已知骨再生动力学的小型猪下颌骨髁状突承载部位测试支架。使用三维定量显微CT、力学测试和组织学方法，确定4周和8周时，模数/孔隙率与骨再生之间的关系。这些结果将提供关于承载所需的模数以及设计的孔隙率/渗透率如何影响骨再生的定量信息。这些信息将为支架设计提供指导，以优化从支架承载到骨再生和承载的过渡。

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.