Abstract

The fabrication technique determines the physicochemical and biological properties of scaffolds, including the porosity, mechanical strength, osteoconductivity, and bone regenerative potential. Biphasic calcium phosphate (BCP)-based scaffolds are superior in bone tissue engineering due to their suitable physicochemical and biological properties. We developed an indirect selective laser sintering (SLS) printing strategy to fabricate 3D microporous BCP scaffolds for bone tissue engineering purposes. The green part of the BCP scaffold was fabricated by SLS at a relevant low temperature in the presence of epoxy resin (EP), and the remaining EP was decomposed and eliminated by a subsequent sintering process to obtain the microporous BCP scaffolds. Physicochemical properties, cell adhesion, biocompatibility, in vitro osteogenic potential, and rabbit critical-size cranial bone defect healing potential of the scaffolds were extensively evaluated. This indirect SLS printing eliminated the drawbacks of conventional direct SLS printing at high working temperatures, i.e. wavy deformation of the scaffold, hydroxyapatite decomposition, and conversion of β-tricalcium phosphate (TCP) to α-TCP. Among the scaffolds printed with various binder ratios (by weight) of BCP and EP, the scaffold with 50/50 binder ratio (S4) showed the highest mechanical strength and porosity with the smallest pore size. Scaffold S4 showed the highest effect on osteogenic differentiation of precursor cells in vitro, and this effect was ERK1/2 signaling-dependent. Scaffold S4 robustly promoted precursor cell homing, endogenous bone regeneration, and vascularization in rabbit critical-size cranial defects. In conclusion, BCP scaffolds fabricated by indirect SLS printing maintain the physicochemical properties of BCP and possess the capacity to recruit host precursor cells to the defect site and promote endogenous bone regeneration possibly via the activation of ERK1/2 signaling.