NIR-Activatable Antibacterial 3D-Printed Hydrogel Scaffold with Controllable Drug Release for Enhanced Vascularized Bone Regeneration

Abstract

Three-dimensional (3D)-printed scaffolds have been extensively researched in the field of tissue engineering for their exceptional biocompatibility as well as precise regenerative capabilities. However, developing photothermal-responsive scaffolds that exhibit near-infrared (NIR)-activatable mechanical shrinkage for controlled and highly sensitive drug release remains a significant challenge in achieving efficient and rapid bone repair. In this article, we designed a 3D-printed hydrogel scaffold (DFO-Au@GN) composed of deferoxamine (DFO)-loaded gold nanoparticles (AuNPs), gelatin methacrylate (GelMA), and N-isopropylacrylamide (NIPAM) to promote superior vascularized osteogenesis. The AuNPs were synthesized in a single step using gelatin as both the reducing agent and stabilizer, which not only demonstrated high drug loading efficiency but also imparted excellent photothermal conversion performance, mechanical and osteogenic properties to the scaffold. The composite scaffold exhibited a shrinkage property when irradiated by 808 nm NIR light, facilitating the controlled release of DFO and AuNPs. In vitro studies indicated that the heat generated by AuNPs effectively eradicated bacteria, thereby addressing the early infections associated with scaffold implantation. Additionally, the DFO-Au@GN scaffold efficiently stimulated angiogenesis from the activation of the hypoxia-inducible factor 1α (HIF-1α) signaling pathway and enhanced the ossification of bone marrow mesenchymal stem cells (BMSCs). The multifunctional scaffold was further demonstrated to significantly improve the repair efficiency of rat calvarial defects through the combined influence of mild thermal stimulation and biochemical induction and promote the formation of H-type vessels for the coupling of angiogenesis and osteogenesis from the results of animal experiments. Therefore, the DFO-Au@GN scaffold, in conjunction with NIR-triggered mild heat stimulation, holds considerable promise for the efficient and rapid treatment of bone defects.

Keywords: 3D printing; antibacterial activity; heat stimulation; photothermal responsiveness; vascularized bone regeneration.