Scalable fabrication of freely shapable 3D hierarchical Cu-doped hydroxyapatite scaffolds via rapid gelation for enhanced bone repair

Abstract

Critical-sized bone defects present a formidable challenge in tissue engineering, necessitating innovative approaches that integrate osteogenesis and angiogenesis for effective repair. Inspired by the hierarchical porous structure of natural bone, this study introduces a novel method for the scalable production of ultra-long, copper-doped hydroxyapatite (Cu-HAp) fibers, utilizing the rapid gelation properties of guar gum (GG) under controlled conditions. These fibers serve as foundational units to fabricate three-dimensional porous scaffolds with a biomimetic hierarchical architecture. The scaffolds exhibit a broad pore size distribution (1–500 μm) and abundant nanoporous features, mimicking the native bone extracellular matrix. Physicochemical characterization and in vitro assays demonstrated that the copper doping significantly enhanced osteogenic and angiogenic activities, with optimized concentrations (0.8 % and 1.2 % Cu) facilitating the upregulation of osteogenesis-related genes and proteins, as well as promoting endothelial cell proliferation. In vivo studies further confirmed the scaffolds' efficacy, with the 1.2Cu-HAp group showing a remarkable increase in bone regeneration (bone volume/total volume ratio: 35.7 ± 1.87 %) within the defect site. This research offers a promising strategy for the rapid fabrication of multifunctional scaffolds that not only support bone tissue repair but also actively accelerate the healing process through enhanced vascularization.