A time-dependent mechanobiology-based topology optimization to enhance bone growth in tissue scaffolds

Scaffold-based bone tissue engineering has been extensively developed as a potential means to treatment of large bone defects. To enhance the biomechanical performance of porous tissue scaffolds, computational design techniques have gained growing popularity attributable to their compelling efficiency and strong predictive features compared with time-consuming trial-and-error experiments. Nevertheless, the mechanical stimulus necessary for bone regeneration, which characterizes dynamic nature due to continuous variation in the bone-scaffold construct system as a result of bone-ingrowth and scaffold biodegradation, is often neglected. Thus, this study proposes a time-dependent mechanobiology-based topology optimization framework for design of tissue scaffolds, thereby developing an ongoing favorable microenvironment and ensuring a long-term outcome for bone regeneration. For the first time, a level-set based topology optimization algorithm and a time-dependent shape derivative are developed to optimize the scaffold architecture. In this study, a large bone defect in a simulated 2D femur model and a partial defect in a 3D femur model are considered to demonstrate the effectiveness of the proposed design method. The results are compared with those obtained from stiffness-based topology optimization, time-independent design and typical scaffold constructs, showing significant advantages in continuing bone ingrowth outcomes.