Enhancing bone regeneration through 3D printed biphasic calcium phosphate scaffolds featuring graded pore sizes

Human long bones exhibit pore size gradients with small pores in the exterior cortical bone and large pores in the interior cancellous bone. However, most current bone tissue engineering (BTE) scaffolds only have homogeneous porous structures that do not resemble the graded architectures of natural bones. Pore-size graded (PSG) scaffolds are attractive for BTE since they can provide biomimicking porous structures that may lead to enhanced bone tissue regeneration. In this study, uniform pore size scaffolds and PSG scaffolds were designed using the gyroid unit of triply periodic minimal surface (TPMS), with small pores (400 μm) in the periphery and large pores (400, 600, 800 or 1000 μm) in the center of BTE scaffolds (designated as 400-400, 400-600, 400-800, and 400-1000 scaffold, respectively). All scaffolds maintained the same porosity of 70 vol%. BTE scaffolds were subsequently fabricated through digital light processing (DLP) 3D printing with the use of biphasic calcium phosphate (BCP). The results showed that DLP 3D printing could produce PSG BCP scaffolds with high fidelity. The PSG BCP scaffolds possessed improved biocompatibility and mass transport properties as compared to uniform pore size BCP scaffolds. In particular, the 400-800 PSG scaffolds promoted osteogenesis in vitro and enhanced new bone formation and vascularization in vivo while they displayed favorable compressive properties and permeability. This study has revealed the importance of structural design and optimization of BTE scaffolds for achieving balanced mechanical, mass transport and biological performance for bone regeneration.