3D-printed multifunctional composite scaffolds incorporating copper ions/amoxicillin/hydroxyapatite for synergistic...

The repair of large bone defects presents significant clinical challenges due to the complex healing process involving early infection control, followed by angiogenesis and osteogenesis. However, conventional biological scaffolds often fail to support these sequential stages, limiting their effectiveness in achieving complete and functional bone regeneration. To address this challenge, a multifunctional vascularized composite bone scaffold was fabricated in this study using 3D printing technology, utilizing gelatin (GEL) and sodium alginate (SA) as the hydrogel matrix, with incorporation of copper ions (Cu²⁺) and amoxicillin (AMX)-loaded hydroxyapatite microspheres (mHAPs@AMX). The rapid initial release and synergistic action of Cu²⁺ and AMX effectively enhanced early-stage antibacterial activity. Subsequently, the sustained release of Cu²⁺ promoted angiogenesis, while the combined effects of Cu²⁺ and mHAPs synergistically enhanced later-stage osteogenesis. The fabricated scaffold demonstrated excellent physicochemical characteristics, along with effective antibacterial and drug release properties. Furthermore, in vitro cell studies and in vivo animal models of rat skull defect repair further validated that the fabricated scaffold had superior biocompatibility and capacity to promote vascularized bone regeneration, highlighting its potential for clinical application for repairing large bone defects.