Indirect selective laser sintering printed microporous biphasic calcium phosphate scaffold promotes endogenous bone regeneration via activation of ERK1/2 signaling.

Fabrication technique determines the physicochemical and biological properties of scaffold, including 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 BCP scaffold was fabricated by SLS at relevantly 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-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 cells homing, endogenous bone regeneration, and vascularization in rabbit critical-size cranial defect. In conclusion, BCP scaffold fabricated by indirect SLS printing maintains the physicochemical properties of BCP and possess the capacity to recruit host precursor cells to the defect site and promote the endogenous bone regeneration possibly via activation of ERK1/2 signaling.