Relative Influence of Scaffold Design/Material Parameters On Bone Regeneration

描述（由申请人提供）：骨支架应提供足够的承重和增强组织再生。然而，目前，很少有严格的比较信息可以告诉人们，给定的材料与给定的建筑设计将提供足够的承载和最好的骨再生。作为出发点，我们将承重与有效弹性和强度联系起来，并将增强组织再生与渗透性材料作为设计变量。那么根本的问题就变成了“支架能否在设计时保持最小的承载特性，同时最大化通透性？相对于材料的骨导电性，通透性对于骨再生有多重要？”我们假设骨组织工程支架应该采用最具导骨性和最大通透性的材料来制造，以促进骨再生。此外，支架的设计应使时间0时的力学性能达到模量50 MPa和抗压强度2 MPa，在人体小梁骨的范围内。与此假设相关，我们试图回答以下问题：1)支架能否设计成满足最小50/2 MPa刚度/强度标准，这些机械性能的退化如何取决于渗透率和材料？2)通透性在骨再生中起重要作用还是材料是一个压倒性的因素？我们将通过三个具体目标来回答这些基本的支架设计问题：具体目标1：在单一孔隙率为60%、渗透率为最大和次最大的情况下，通过计算设计和制造HA/TCP、PLLA和PCL的支架结构。具体目标2：确定设计的支架在0满足人体小梁骨最小值时的弹性模量和极限强度。确定设计/材料如何影响机械性能的退化。具体目标3：通过传递BMP-7转导的人成纤维细胞，确定设计的通透性和材料对小鼠模型8周和16周骨再生的影响。该研究将为骨组织工程师提供关于支架通透性和材料骨组织支架设计相对重要性的关键信息，这将对临床骨组织工程应用至关重要。

DESCRIPTION (provided by applicant): Bone scaffolds should provide adequate load bearing and enhance tissue regeneration. However, at present, there is little rigorous comparative information that will tell one that a given material with a given architecture design will provide adequate load bearing and give the best bone regeneration. As a starting point, we associate load bearing with effective elasticity and strength, and enhanced tissue regeneration with permeability material as design variables. Then the fundamental question becomes "can scaffolds be designed to maintain minimum loading bearing characteristics while maximizing permeability and how important is permeability for bone regeneration relative to material osteoconductivity?" We hypothesize that Bone tissue engineering scaffolds should be fabricated from the most osteoconductive material with maximal permeability to enhance bone regeneration. Furthermore, the scaffold design should be such that the mechanical properties at time 0 can achieve a modulus of 50 MPa and compressive strength of 2 MPa, within the range of human trabecular bone. Related to this hypothesis, we seek to answer the questions: 1) can scaffolds be designed to meet the minimum 50/2 MPa stiffness/strength criteria and how does degradation of these mechanical properties depend on permeability and material?, and 2) does permeability play a significant role in bone regeneration or is material an overwhelming factor? We will answer these fundamental scaffold design questions through three specific aims: Specific Aim 1: Computationally design and fabricate scaffolds architectures from HA/TCP, PLLA, and PCL at a single porosity of 60% with maximal and sub-maximal permeability Specific Aim 2: Determine elastic modulus and ultimate strength of designed scaffolds at 0 meet minimum human trabecular bone values. Determine how design/material influence degradation of mechanical properties. Specific Aim 3: Determine the influence of designed permeability and material on bone regeneration in a mouse model at 8, and 16 weeks by delivering BMP-7 transduced human fibroblasts. This study will give bone tissue engineers critical information as to as to the relative importance of scaffold permeability and material bone tissue scaffold design, which will be crucial for clinical bone tissue engineering applications.