Optimizing Mandibular Scaffold Modulus/Porosity Balance

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/支架功能到完全天然骨的转变，但几乎没有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和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了“模量和互连的孔隙率/渗透率之间的正确平衡是什么，使得支架可以承受载荷，直到再生组织可以承受载荷？".为了回答这个关键问题，我们必须能够设计支架结构与特定的模量孔隙率关系，制造这些复杂的支架骨工程材料，并测试这些支架在一个良好的特点，在体内承重模型。 我们的总体假设是，能够承载载荷的最小刚度支架（刚度等于模量）与最高互连孔隙率/渗透率将实现最佳骨再生。我们的目标是在体内功能性承重部位中定义“最小刚度”和“最高孔隙率/渗透率”。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设计具有四种模量/孔隙率比的支架架构，这些比在最初和降解后跨越理论Hashin-Shtrikman界限。 具体目标2。使用固体自由成型制造技术从PPF/TCP制造设计的支架结构。Micro-CT支架检查架构并测量支架渗透性。 具体目的3.在具有已知骨再生动力学的小型猪下颌骨髁突承重部位测试支架。使用3D定量显微CT、力学测试和组织学确定模量/孔隙率比与4周和8周时骨再生的相关性。结果将提供关于承重所需的模量以及设计的孔隙率/渗透率如何影响骨再生的定量信息。这些信息将为设计支架提供指导，以优化从支架承重到骨再生和承重的过渡。

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.