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Tailoring the atomic structure of advanced sol-gel materials for regenerative medicine through high-performance computing

通过高性能计算定制用于再生医学的先进溶胶凝胶材料的原子结构

基本信息

批准号：
EP/M004201/1
负责人：
Antonio Tilocca
金额：
$ 25.81万
依托单位：
University College London
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2015
资助国家：
英国
起止时间：
2015 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FM004201%2F1
关键词：
Tailoring atomic structure advanced sol

项目摘要

Increasing life expectancy is resulting in a growing number of surgical procedures to repair weakened or damaged tissues, such as bone and cartilage, with an increasing use of synthetic biomaterials. Current biomaterials used to replace living tissues are unable to cope with ongoing changes in the physiological environment, which is at odds with the tissues, that can self-repair while dynamically adapting to the local conditions. Next-generation biomaterials must be able to trigger the natural self-repair mechanisms of the body, providing a framework which stimulates cells to regenerate new tissues. Many therapies require the delivery of drugs, but the polymer capsules that deliver them degrade rapidly, releasing all the drug in one go, not necessarily in the right place. The sol-gel process, which assembles silica networks through a chemistry approach, allows one to make biodegradable silica nanoparticles that can deliver drugs or active ions where they are needed. Materials for tissue regeneration will ideally combine efficient biointegration, controllable biodegradability and cell-stimulation capabilities. Despite their proven ability to trigger the activity of cells that create new tissues, the potential of conventional melt-derived bioglasses (BGs) as next-generation biomaterials is limited by incomplete biodegradation and the difficulty to incorporate them in scaffold templates for tissue-engineering. BGs obtained through a sol-gel route show superior properties, such as higher and controlled solubility; the mild temperature of the sol-gel process allows scaffolds for tissue-engineering to be made, and also allows the incorporation of polymers to make hybrid materials with higher toughness and tighter control of biodegradability than bioceramics. Hybrids are potentially able to share the load with host tissue and respond to biomechanical stimuli.If any of this potential is to be fulfilled, it is critical to understand the evolution of the nanostructure during synthesis and how to incorporate cations, such as calcium, which affect the material's degradation rate and functionality.This project will apply breakthrough computer simulations to show how adjustable variables in the sol-gel process, e.g. chemical nature of the precursors (particularly the calcium source), solution pH and stabilisation temperature, affect the nanostructure of the particles, and thus their performance. Such simulations have not been possible previously. The knowledge gained will enable better control over the material behaviour, for instance enabling tailoring the degradation rate of a scaffold to the growth of the target tissue to be regenerated, and would represent a solid foundation to support the rational development of tissue-regeneration biomaterials incorporating sol-gel BGs as a core component. If substantial advances are to be sought in Biomaterials research, a more fundamental approach to understand the effects which steer the material's behaviour is now required, beyond established but expensive and intrinsically limited trial-and-error approaches. The huge rise in available computer power and methods now enables us to tackle challenges which were out of reach only a few years ago, such as directly modelling the dynamical changes in the sol-gel synthesis, like multiple polymerisation and condensation reactions between modified silica nanoparticles in solution. We thus now have the unique opportunity to gain fundamental insight which will be a key reference not only for the biomaterials community but also for chemists, engineers and materials scientists who use soft chemistry processing routes. The results from this project will support biomedical and biomaterial research towards better materials for regenerative medicine. These advances will lead in the future to more effective longer-term treatments of musculoskeletal traumas and diseases, especially in older people, with large social and economical benefits.

预期寿命的增加导致越来越多的外科手术来修复弱化或受损的组织，例如骨骼和软骨，并越来越多地使用合成生物材料。目前用于替代活组织的生物材料无法应对生理环境的持续变化，这与组织不一致，可以自我修复，同时动态适应局部条件。下一代生物材料必须能够触发身体的自然自我修复机制，提供一个刺激细胞再生新组织的框架。许多疗法都需要药物的输送，但输送药物的聚合物胶囊会迅速降解，一次性释放所有药物，而不一定是在正确的位置。溶胶-凝胶过程通过化学方法组装二氧化硅网络，允许人们制造可生物降解的二氧化硅纳米颗粒，可以在需要的地方提供药物或活性离子。用于组织再生的材料将理想地结合联合收割机有效的生物整合、可控的生物降解性和细胞刺激能力。尽管它们被证明有能力触发产生新组织的细胞的活性，但传统的熔融衍生生物玻璃（BG）作为下一代生物材料的潜力受到不完全生物降解和难以将其纳入组织工程支架模板的限制。通过溶胶-凝胶途径获得的BG显示出优异的上级性质，例如更高的和受控的溶解度;溶胶-凝胶过程的温和温度允许制备用于组织工程的支架，并且还允许掺入聚合物以制备具有比生物陶瓷更高的韧性和更严格的生物降解性控制的杂化材料。杂化材料有可能与宿主组织分担负载并对生物力学刺激做出反应。如果要实现任何这种潜力，关键是要了解合成过程中纳米结构的演变以及如何引入影响材料降解速率和功能的阳离子，如钙。该项目将应用突破性的计算机模拟来展示溶胶-凝胶过程中的可调节变量，例如前体（特别是钙源）的化学性质、溶液pH和稳定化温度，影响颗粒的纳米结构，从而影响它们的性能。这种模拟在以前是不可能的。所获得的知识将能够更好地控制材料行为，例如能够根据待再生的靶组织的生长来定制支架的降解速率，并且将代表支持将溶胶-凝胶BG作为核心组分的组织再生生物材料的合理开发的坚实基础。如果要在生物材料研究中寻求实质性的进展，现在需要一种更基本的方法来理解引导材料行为的影响，超越已建立但昂贵且内在有限的试错方法。可用计算机能力和方法的巨大增长现在使我们能够应对几年前无法实现的挑战，例如直接模拟溶胶-凝胶合成中的动态变化，例如溶液中改性二氧化硅纳米颗粒之间的多重聚合和缩合反应。因此，我们现在有独特的机会获得基本的见解，这将是一个关键的参考，不仅为生物材料界，而且为化学家，工程师和材料科学家谁使用软化学加工路线。该项目的结果将支持生物医学和生物材料研究，以获得更好的再生医学材料。这些进展将在未来导致更有效的长期治疗肌肉骨骼创伤和疾病，特别是在老年人中，具有巨大的社会和经济效益。