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Simulation Guided Manufacturing of Synthetic Bone

仿真引导合成骨制造

基本信息

批准号：
2127263
负责人：
金额：
--
依托单位：
Newcastle University
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2018
资助国家：
英国
起止时间：
2018 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=studentship-2127263
关键词：
Simulation Guided Manufacturing Synthetic Bone

项目摘要

The focus of this research is to bridge two traditionally distant fields, high-performance simulations of cement formation and experimental synthesis of scaffolds in tissue engineering to enhance bone regeneration. The simulations will be iterated and validated with in vitro experiments to assess hydroxyapatite (HA) precipitation on collagen-based polymeric substrates [bone contains Calcium Phosphate (Ca/P) (69-80 wt. %) (Mainly HA), Collagen (17-20 wt. %), water, and proteins etc.]. The optimisation of these materials will be performed experimentally by assessing the mechanical and biological performance at different concentrations of polymer and Ca/P or HA. The key idea is that the experiments can be guided by novel high performance simulations of the self-assembly of collagen-polymer scaffolds and of bone tissue precipitation. At the end of this project, the main outcome will be to develop by simulation and produce, in vitro, a set of new bio-polymer or composite scaffolds with enhanced biological and mechanical properties ideally leading to a scaffold which closely mimics the properties of organic bone; such properties include, porosity, mechanical strength, bioactivity, and degradation rate.Many modern biomaterials have been shown to induce bone formation and repair, however, designing scaffolds which possess the optimal balance of biological and mechanical properties for bone repair is difficult. As such, the aim of this project is to develop an alternative approach for bone scaffold design by using simulations to guide their composition. The resulting simulation guided approach may revolutionise the way in which scaffolds for bone regeneration are designed and manufactured, first in silico (simulation) and then in vitro, by cutting the time and cost of experiments by orders of magnitude. In order to achieve this goal, the project is divided into 3 main objectives:1. To develop a novel high-performance simulation to guide the design and creation of new collagen-based bio-polymers or composites for enhanced bone formation. For this, the in vitro bone formation will be assessed using the biomimetic method (synthetic biochemical process) described by Kokubo et al, and cell experiments on various 2D polymeric substrates used in bone regeneration, which combine biodegradable polymers, collagen and calcium phosphate/apatite at different ratios. By measuring the rate of HA mineral deposition on different substrates, high-performance simulations described by Shvab et al will be adapted and tuned to predict the evolution of bone formation in terms of scaffold composition.2. To develop a novel high-performance simulation to guide the design and manufacturing of 3D porous scaffolds with structural and mechanical integrity capable of improving bone formation. Scaffolds will be manufactured with various porosities and mechanical properties in order to evaluate the effect of substrate morphology on in vitro bone formation. These attributes will be used as design variables and inputs for high-performance simulations to predict and guide bone formation in 3D polymeric scaffolds, requiring just hours of computation.3. To integrate developed mathematical models into a new high-performance simulation able to guide the design and manufacturing of new 3D collagen-based materials with enhanced structural and mechanical properties to improve bone regeneration. At the end of this project, the main outcome will be to produce in silico and in vitro a set of new porous materials with biological and mechanical properties similar to that of bone, capable of promoting greater regeneration rates and amounts of new bone tissue. Developed collagen-based materials will be optimised by the results of combined molecular dynamics and geometric simulations; If successful, this new simulation guided approach could predict and improve structural materials performance and likelihood of success.

这项研究的重点是弥合两个传统上相距甚远的领域：高性能的骨水泥形成模拟和组织工程中促进骨再生的支架实验合成。这些模拟将通过体外实验进行迭代和验证，以评估羟基磷灰石(HA)在胶原基聚合物基质[骨包含磷酸钙(Ca/P)(69-80wt.%)(主要是HA)、胶原(17-20wt.%)、水和蛋白质等]上的沉淀。对这些材料的优化将通过实验进行，方法是评估不同浓度的聚合物和Ca/P或HA的机械和生物性能。其关键思想是，这些实验可以由胶原-聚合物支架的自组装和骨组织沉淀的新的高性能模拟来指导。在这个项目的最后，主要的成果将是通过模拟开发并在体外产生一组新的生物聚合物或复合支架，具有增强的生物和力学性能，理想地导致支架接近于有机骨的性能；这些性能包括孔隙度、机械强度、生物活性和降解率。许多现代生物材料已经被证明可以诱导骨形成和修复，然而，设计具有最佳生物和力学性能平衡的支架用于骨修复是困难的。因此，本项目的目的是开发一种替代方法，通过使用模拟来指导骨支架的组成。由此产生的模拟引导方法可能会彻底改变骨再生支架的设计和制造方式，首先是在硅胶(模拟)中，然后是在体外，通过将实验的时间和成本减少数量级来实现。为了实现这一目标，该项目分为三个主要目标：1.开发一种新颖的高性能模拟，以指导设计和创造新的胶原基生物聚合物或复合材料，以促进骨形成。为此，将使用Kokubo等人描述的仿生方法(合成生化过程)以及在用于骨再生的各种2D聚合物基质上进行细胞实验来评估体外骨形成，这些2D聚合物基质以不同的比例结合可生物降解的聚合物、胶原和磷酸钙/磷灰石。通过测量羟基磷灰石在不同基质上的沉积速率，Shvab等人描述的高性能模拟将被适应和调整，以预测支架成分方面的骨形成演变。开发一种新的高性能模拟来指导三维多孔支架的设计和制造，该支架具有结构和机械完整性，能够促进骨形成。为了评估基质形态对体外成骨的影响，将制备具有不同孔隙率和力学性能的支架。这些属性将被用作高性能模拟的设计变量和输入，以预测和指导3D聚合支架中的骨形成，只需要几个小时的计算。将开发的数学模型集成到新的高性能模拟中，能够指导新型3D胶原基材料的设计和制造，这些材料具有增强的结构和机械性能，以改善骨再生。在该项目结束时，主要成果将是在硅胶和体外生产一套新的多孔材料，具有与骨相似的生物和机械性能，能够促进更大的再生速度和新骨组织的数量。开发的胶原基材料将通过结合分子动力学和几何模拟的结果进行优化；如果成功，这种新的模拟指导方法可以预测和改善结构材料的性能和成功的可能性。