3D-printed near-infrared-light-responsive on-demand drug-delivery scaffold for bone regeneration

Abstract

Abstract Background: Although bioactive 3D-printed bone scaffolds loaded with multiple kinds of biomolecules have been developed for enhanced bone regeneration, the manipulation of the on-demand release profiles of different biomolecules during bone regeneration remains challenging. Method: In this study, we fabricated a 3D-printed dual-drug-loaded biomimetic scaffold. The near-infrared (NIR) light-responsive polydopamine-coated hydroxyapatite nanoparticles were designed to deliver the osteogenic drug, pargyline (PGL). Further, a chemotactic small-molecule drug, simvastatin (SIM), was directly incorporated into the hydroxyapatite/collagen bioink for 3D printing. We then evaluated the morphological, mechanical, photothermal properties of scaffold as well as the in vitro releasing profiles of SIM and PGL. Cell proliferation, adhesion, migration and osteogenic differentiation were investigated. The rabbit cranial defect model was utilized to evaluated the in vivo new bone formation. Results: Our scaffold displayed an on-demand sequential release of the two drugs, in which the SIM could be rapidly released during the early stage and the PGL could be released in a NIR light-responsive manner. This on-demand releasing profiles could optimize their therapeutic effects to align with the stem cell recruitment and osteoblastic differentiation, thereby promoting bone regeneration. The results confirmed the suitable mechanical strength, high photothermal conversion efficiency, good biocompatibility of our scaffold. The scaffold loaded with SIM could efficiently accelerate the migration of stem cells. In addition, the scaffold with on-demand sequential release promoted alkaline phosphatase (ALP) activity, significantly upregulated gene expression levels of osteogenesis-related markers, and enhanced new-bone-formation capabilities in rabbit cranial defect models. Conclusion: Our 3D-printed scaffold performs an on-demand delivery of drugs and enhanced bone regeneration. This scaffold not only offers a promising strategy to control the behavior of stem cells during bone regeneration but also provides an efficient strategy for controllable sequential release of different biomolecule in bone tissue engineering.