Title: Tailoring the atomic structure of advanced sol-gel materials for regenerative medicine through high-performance computing
Funder: Engineering and Physical Sciences Research Council

Abstract: 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.


Research activity codes: 1.3 CHEMICAL AND PHYSICAL SCIENCES
Health categories: GENERIC HEALTH RELEVANCE