Bayesian computer-aided experimental design of heterogeneous scaffolds for tissue engineering

This paper presents a Bayesian methodology for computer-aided experimental design of heterogeneous scaffolds for tissue engineering applications. These heterogeneous scaffolds have spatial distributions of growth factors designed to induce and direct the growth of new tissue as the scaffolds degrade. While early scaffold designs have been essentially homogenous, new solid freeform fabrication (SFF) processes enable the fabrication of more complex, biologically inspired heterogeneous designs with controlled spatial distributions of growth factors and scaffold microstructures. SFF processes dramatically expand the number of design possibilities and significantly increase the experimental burden placed on tissue engineers in terms of time and cost. Therefore, we use a multi-stage Bayesian surrogate modeling methodology (MBSM) to build surrogate models that describe the relationship between the design parameters and the therapeutic response. This methodology is well suited for the early stages of the design process because we do not have accurate models of tissue growth, yet the success of our design depends on understanding the effect of the spatial distribution of growth factors on tissue growth. The MBSM process can guide experimental design more efficiently than traditional factorial methods. Using a simulated computer model of bone tissue regeneration, we demonstrate the advantages of Bayesian versus factorial methods for designing heterogeneous fibrin scaffolds with spatial distributions of growth factors enabled by a new SFF process.