Investigation of mechanism of bone regeneration in a porous biodegradable calcium phosphate (CaP) scaffold by a combination of a multi-scale agent-based model and experimental optimization/validation

Abstract

Herein, we have developed a novel approach to investigate the mechanism of bone regeneration in a porous biodegradable calcium phosphate (CaP) scaffold by a combination of a multi-scale agent-based model, experimental optimization of key parameters and experimental data validation of the predictive power of the model. The advantages of this study are that the impact of mechanical stimulation on bone regeneration in a porous biodegradable CaP scaffold is considered, experimental design is used to investigate the optimal combination of growth factors loaded on the porous biodegradable CaP scaffold to promote bone regeneration and the training, testing and analysis of the model are carried out by using experimental data, a data-mining algorithm and related sensitivity analysis. The results reveal that mechanical stimulation has a great impact on bone regeneration in a porous biodegradable CaP scaffold and the optimal combination of growth factors that are encapsulated in nanospheres and loaded into porous biodegradable CaP scaffolds layer-by-layer can effectively promote bone regeneration. Furthermore, the model is robust and able to predict the development of bone regeneration under specified conditions.

Figure 1

Schematic of the computational flow

Figure 2

(a) Workflow of the computational algorithm (b) Finite element analysis model

Figure 3

3D bone formation and 2D slices of bone formation over time. (a), (b) and (c) show the 3D model under mechanical stimulation on days 10, 20 and 28, respectively. (d), (e) and (f) show 2D slices of bone formation on days 10, 20 and 28, respectively. The porous CaP scaffold, MSC, OBa, angiogenesis and pore structure are colored cyan, yellow, blue, red and white, respectively.

Figure 4

Dynamics of MSC (a), OBp (b) and OBa (c) over 28 days.

Figure 5

Results of training (a) and testing (b)