Relative Influence of Scaffold Design/Material Parameters On Bone Regeneration

支架设计/材料参数对骨再生的相对影响

基本信息

批准号：
7656840
负责人：
Scott J Hollister
金额：
$ 36.79万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-08-01 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7656840
关键词：
Address Affect Animal Model Architecture Binding Biocompatible Materials Bone Regeneration Bone Tissue Cells Characteristics Clinical Compressive Strength Coupled Coupling Data Descriptor Elasticity Engineering Experimental Designs Fibroblasts Generations Gingiva Guidelines Human Image In Vitro Measures Mechanics Modeling Mus Natural regeneration Orthopedics Osteogenesis Outcome Permeability Platelet Factor 4 Play Porosity Principal Investigator Property Relative (related person)Research Research Personnel Role Sampling Spinal Techniques Technology Tensile Strength Testing Time Tissue Engineering Tissues Vascularization Weight-Bearing state Work base bone bone engineering bone morphogenetic protein 7 calcium phosphate cellular transduction comparative craniofacial design gene therapy in vivo meetings mouse model poly-L-lactic acid polycaprolactone programs reconstruction scaffold subcutaneous substantia spongiosa tissue regeneration tissue support frame

项目摘要

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.

描述（由申请人提供）：骨支架应提供足够的负载并增强组织再生。然而，目前几乎没有严格的比较信息可以告诉人们，具有给定结构设计的给定材料将提供足够的承载力并提供最佳的骨再生。作为起点，我们将承载与有效弹性和强度相关联，并将增强组织再生与渗透性材料相关联作为设计变量。那么基本问题就变成了“支架的设计能否在保持最小承载特性的同时最大化渗透性？相对于材料的骨传导性，渗透性对于骨再生有多重要？”我们假设骨组织工程支架应该由最具骨传导性且具有最大渗透性的材料制成，以增强骨再生。此外，支架设计应使得0时刻的力学性能能够达到50 MPa的模量和2 MPa的抗压强度，在人体骨小梁的范围内。与这一假设相关，我们试图回答以下问题：1) 支架的设计能否满足最低 50/2 MPa 刚度/强度标准，以及这些机械性能的退化如何取决于渗透性和材料？ 2) 渗透性与渗透性有什么关系？在骨再生中发挥重要作用还是材料是压倒性因素？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：通过计算设计和制造由 HA/TCP、PLLA 和 PCL 制成的支架结构，其单一孔隙率为 60%，具有最大和次最大渗透性具体目标 2：确定设计支架在 0 时的弹性模量和极限强度是否满足人体小梁骨的最低值。确定设计/材料如何影响机械性能的退化。具体目标 3：通过递送 BMP-7 转导的人成纤维细胞，确定设计的渗透性和材料对 8 周和 16 周小鼠模型骨再生的影响。这项研究将为骨组织工程师提供关于支架渗透性和材料骨组织支架设计的相对重要性的关键信息，这对于临床骨组织工程应用至关重要。