Artesunate-loaded hydrogel promotes osteogenic differentiation and bone regeneration under inflammation: An in vitro
Cuicui Zhao1, Xiaofei Dong1, Han Zhu1
1Department of Prosthodontics, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing, Jiangsu 210008, PR China.
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, 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 S 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 Significance:
The AS/GelMA hydrogel promoted the repair of mandibular inflammatory bone defects in rats by coordinating anti-inflammatory and pro-osteogenic activities. This offers a promising biomaterial strategy for addressing residual inflammation-related bone loss in oral and maxillofacial surgery.
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