Scaffold-based tissue engineering requires a resorbable scaffold that can restore function and guide regeneration. Recent advances in material fabrication have expanded our control of compositional and architectural features to approach the complexity of native tissue. However, iterative scaffold design to balance multiple design targets toward optimizing regenerative performance remains both challenging and time-consuming. The number of design parameter combinations for scaffold manufacturing to achieve target properties is nearly limitless. Although a trial-and-error experimental approach may lead to a favorable scaffold design, the time and costs associated with such an approach are enormous. Computational optimization approaches are well suited to sample such a multidimensional design space and streamline the identification of target scaffold parameters for experimental evaluation. In this computational biomechanics approach, target fabrication parameters are identified by using a computational model to iterate across design parameter combinations (input) and predict the resulting graft properties (output). Herein, we describe the three key stages of this model-directed scaffold design: (1) model development, verification, and validation; (2) in silico optimization; and (3) model-directed scaffold fabrication and testing. Although there are several notable examples that have demonstrated the potential of this approach, additional accurate and physiologically appropriate computational simulations are needed to expand its utility across the field. In addition, continued advances in material fabrication are needed to provide the requisite control and resolution to produce the model-directed design. Finally, and most importantly, active collaboration between experts in materials science and computational modeling are critical to realize the full potential of this approach to accelerate scaffold development.
Keywords: advanced manufacturing; biomaterials; in silico optimization; model-directed design; tissue engineering.