Redefining architectural effects in 3D printed scaffolds through rational design for optimal bone tissue regeneration

Internal architecture of tissue scaffolds plays a significant role in their ability to heal critical-size bone defects. Many studies have investigated these effects but lack isolating architectural features in 3D space, hindering optimization of pore shape to improve bone ingrowth and consequently clinical outcome. To address this challenge, we developed a systematic design strategy and a high-fidelity and-precision ceramic printing technique using a stereolithography desktop printer. We used these techniques to print 5 scaffold architectures with different surface convexities/concavities, pore interconnectivities, and permeabilities, while maintaining the same porosity, average pore size, and surface area. We determined the mechanical effects of the architecture using mechanical tests with in-situ imaging, finite element, and computational fluid dynamic simulations. The effects of architecture on bioactivity and bone ingrowth were determined in a rabbit calvarial critical-size defect model at 12-week implantation, using mu-computed tomography, and histology. The results showed that bone ingrowth is significantly affected by pore interconnectivity in 3D space and maximum fluid permeability in 3D regardless of flow direction, but not permeability in one or few directions. Surface convexity/concavity did not affect bone formation in our 3D scaffolds. Bone ingrowth in scaffolds with highly interconnected pores resulted in a significantly tougher and stronger bioceramic/bone composites, compared to the inherently brittle scaffolds pre-implantation. Our findings provide a rational design of 3D scaffolds architectures for effective translation to the clinic and could be used to predict the tissue regeneration capacity of scaffolds with other architectures or made of other materials. (c) 2021 Elsevier Ltd. All rights reserved.

Automated summary

This study investigated the effects of internal architecture of tissue scaffolds on healing critical-size bone defects. Results showed that pore interconnectivity and maximum fluid permeability in 3D space significantly impacted bone ingrowth, while surface convexity/concavity did not affect bone formation. High interconnected pore structures in scaffolds resulted in significantly tougher and stronger bioceramic/bone composites post-implantation.