Virtual Design of 3D-Printed Bone Tissue Engineered Scaffold Shape Using Mechanobiological Modeling: Relationship of Scaffold Pore Architecture to Bone Tissue Formation

Large bone defects are clinically challenging, with up to 15% of these requiring surgical intervention due to non-union. Bone grafts (autographs or allografts) can be used but they have many limitations, meaning that polymer-based bone tissue engineered scaffolds (tissue engineering) are a more promising solution. Clinical translation of scaffolds is still limited but this could be improved by exploring the whole design space using virtual tools such as mechanobiological modeling. In tissue engineering, a significant research effort has been expended on materials and manufacturing but relatively little has been focused on shape. Most scaffolds use regular pore architecture throughout, leaving custom or irregular pore architecture designs unexplored. The aim of this paper is to introduce a virtual design environment for scaffold development and to illustrate its potential by exploring the relationship of pore architecture to bone tissue formation. A virtual design framework has been created utilizing a mechanical stress finite element (FE) model coupled with a cell behavior agent-based model to investigate the mechanobiological relationships of scaffold shape and bone tissue formation. A case study showed that modifying pore architecture from regular to irregular enabled between 17 and 33% more bone formation within the 4-16-week time periods analyzed. This work shows that shape, specifically pore architecture, is as important as other design parameters such as material and manufacturing for improving the function of bone tissue scaffold implants. It is recommended that future research be conducted to both optimize irregular pore architectures and to explore the potential extension of the concept of shape modification beyond mechanical stress to look at other factors present in the body.

Automated summary

Large bone defects can be challenging clinically, and using polymer-based bone tissue engineered scaffolds shows promise as a solution. However, the clinical translation of such scaffolds is limited, and exploring the design space using virtual tools like mechanobiological modeling can improve this. This paper introduces a virtual design environment for scaffold development and demonstrates the potential of pore architecture in influencing bone tissue formation. The study shows that modifying pore architecture can significantly increase bone formation, suggesting that shape is as important as other design parameters for scaffold implants.