Simulation Guided Manufacturing of Synthetic Bone

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.