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

随着合成生物材料的使用越来越多，预期寿命的延长导致了越来越多的外科手术，以修复骨骼和软骨等虚弱或受损的组织。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，这种变化与组织不一致，可以在动态适应当地条件的同时进行自我修复。下一代生物材料必须能够触发人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。许多疗法需要药物输送，但输送药物的聚合物胶囊会迅速降解，一次释放所有药物，不一定是在正确的地方。溶胶凝胶法通过化学方法组装二氧化硅网络，使人们能够制造出可生物降解的二氧化硅纳米颗粒，这种纳米颗粒可以将药物或活性离子输送到需要的地方。用于组织再生的材料将理想地结合有效的生物整合、可控的生物降解性和细胞刺激能力。尽管传统的熔融衍生生物玻璃(BGS)已被证明有能力触发细胞的活动来创造新的组织，但作为下一代生物材料的潜力受到不完全生物降解和将它们整合到组织工程支架模板中的困难的限制。通过Sol-Gel方法获得的BGS表现出优异的性能，例如更高且可控的溶解度；Sol-Gel过程的温和温度允许制造用于组织工程的支架，也允许加入聚合物来制备比生物陶瓷具有更高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荷，并对生物力学刺激做出反应。如果要实现这一潜力，关键是要了解合成过程中纳米结构的演变，以及如何结合阳离子，如钙，这将影响材料的降解率和功能。本项目将应用突破性的计算机模拟来展示溶胶-凝胶过程中的可调变量，如前驱体的化学性质(特别是钙源)、溶液pH和稳定温度，影响粒子的纳米结构，从而影响其性能。这样的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的行为，例如能够根据待再生目标组织的生长情况调整支架的降解速度，并将为支持以溶胶-凝胶BGS为核心成分的组织再生生物材料的合理开发奠定坚实的基础。如果要寻求在生物材料研究方面取得实质性进展，现在就需要一种更根本的方法来了解指导材料行为的影响，而不是既定的但昂贵的和内在有限的试错方法。可用的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还遥不可及的挑战，例如直接模拟溶胶-凝胶合成中的动态变化，如改性二氧化硅纳米颗粒在溶液中的多重聚合和缩合反应。因此，我们现在有了一个独特的机会来获得基本的见解，这不仅将是生物材料界的关键参考，也将是使用软化学加工路线的化学家、工程师和材料科学家的关键参考。该项目的结果将支持生物医学和生物材料研究，为再生医学提供更好的材料。这些进展将导致未来对肌肉骨骼创伤和疾病，特别是对老年人的更有效的长期治疗，具有巨大的社会效益和经济效益。

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.