3D-printed nano-hydroxyapatite/polylactic acid scaffold with simvastatin-loaded hydroxyethyl methacrylate/sulfobetaine methacrylate hydrogel for accelerated bone repair

Bone defects resulting from trauma, infection, or tumor resection often exceed the self-healing capacity of bone tissue, requiring bioactive and mechanically robust repair materials. In this study, a composite scaffold was developed via in-situ polymerization of a hydroxyethyl methacrylate/sulfobetaine methacrylate (HEMA/SBMA, abbreviated as HMSM) hydrogel with a 3D-printed nano-hydroxyapatite/polylactic acid (nHAP/PLA, abbreviated as NP) gradient scaffold to achieve controlled simvastatin (SIM) delivery and enhanced osteogenesis. The HMSM hydrogel served as a hydrophilic and biocompatible matrix, while the NP scaffold provided mechanical strength and structural support. SIM was incorporated into the hydrogel–scaffold composite (SIM@HMSM/NP) to establish a sustained drug-release system. The composite exhibited a smooth microstructure, uniform pore distribution, and a gradient architecture mimicking native bone. Mechanical testing demonstrated improved compressive strength compared with individual components, and in vitro studies revealed stable SIM release over 24 days with a degradation profile compatible with bone regeneration. The SIM@HMSM/NP showed excellent cytocompatibility, promoted bone marrow mesenchymal stem cell proliferation and osteogenic differentiation, and significantly enhanced bone formation in a rat calvarial defect model. These findings suggest that the SIM@HMSM/NP scaffold provides a promising strategy for sustained drug delivery and accelerated bone regeneration in critical-sized bone defects.