Three-dimensional-printed hydroxyapatite/nanoclay/polycaprolactone composite scaffold for immunomodulation and bone defect repair

Abstract

Excessive inflammation remains a major impediment to the clinical repair of critical-sized bone defects, with the immune micro-environment playing a pivotal role in osteogenesis. An appropriate local immune response following biomaterial implantation is essential for successful bone tissue regeneration. In this study, a hydroxyapatite/montmorillonite nanoclay/polycaprolactone (HNP) composite scaffold was designed and subsequently fabricated using three-dimensional (3D) printing, with the aim of modulating macrophage polarization and promoting bone regeneration. The resulting HNP scaffold exhibited favorable mechanical strength and significantly promoted bone marrow mesenchymal stem cell adhesion, proliferation, secretion of osteogenic cytokines, and osteogenic differentiation. Moreover, it modulated the bone immune micro-environment by suppressing M1 macrophage polarization and promoting a shift toward the M2 phenotype, thereby establishing a pro-osteogenic immune milieu. In vivo studies using a rat calvarial defect model demonstrated that, compared with other groups, the HNP scaffold markedly enhanced M2 macrophage polarization, promoted angiogenesis, and accelerated new bone formation. Overall, the 3D-printed HNP scaffold effectively regulated the immune micro-environment and facilitated both bone regeneration and neovascularization, highlighting its strong potential as a candidate for bone tissue engineering applications.

Keywords

Bone repair / Hydroxyapatite / Macrophage polarization / Nanoclay / Three-dimensional printing