Abstract

Objective This study aimed to prepare an artesunate (AS)-loaded gelatin methacryloyl (AS/GelMA) composite hydrogel and systematically evaluate its anti-inflammatory and pro-osteogenic effects in a lipopolysaccharide (LPS)-induced inflammatory microenvironment. Methods The AS/GelMA hydrogel was prepared, and its physicochemical properties were characterized by scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, and degradation, rheology, and compression tests. Biocompatibility was assessed by Cell Counting Kit-8, Live/Dead, and cytoskeleton staining, and anti-inflammatory and osteogenic activities were evaluated by quantitative real-time polymerase chain reaction, western blot, immunofluorescence, and Alizarin Red staining of rat bone marrow mesenchymal stem cells (rBMSCs) under LPS-induced inflammation. In vivo rat mandibular inflammatory defect models were constructed and assessed at two and four weeks post-surgery using micro-computed tomography and histological staining. Results The addition of AS enhanced the hydrogel's mechanical strength while maintaining its biocompatibility, interconnected porous structure, and injectability. In vitro , the AS/GelMA hydrogel significantly inhibited the expression of pro-inflammatory factors and significantly promoted osteogenic differentiation and mineralization under inflammation. In vivo , the AS/GelMA group showed no obvious visceral toxicity and accelerated higher-quality new bone formation at two and four weeks compared to controls. Conclusions The AS/GelMA composite hydrogel effectively coordinated dual anti-inflammatory and pro-osteogenic bioactivities, significantly promoting the repair of inflammatory bone defects. Therefore, AS/GelMA represents a promising biomaterial strategy to improve regenerative outcomes under inflammation-compromised conditions. Clinical