Advances in bone regeneration: Photothermal-responsive hydrogel accelerates healing via STING inhibition
image: Schematic illustration of the GMHD/TFe@Aca hydrogel system: (1) Near-infrared (NIR) light triggers controlled release of acacetin from tannic acid-iron nanoparticles; (2) Acacetin inhibits STING pathway, reducing inflammation by suppressing M1 macrophages while promoting M2 polarization; (3) Enhanced bone regeneration occurs through collagen deposition, angiogenesis, and osteogenesis in cranial defects. The hydrogel demonstrates excellent mechanical strength and spatiotemporal drug release capabilities for precision bone repair.
Credit: Shanghai University
Bone defects, caused by trauma, infection, tumors, or osteoporosis, are common clinical issues, with over 8 million new fracture cases and approximately 9 million osteoporotic fractures annually worldwide. Traditional bone graft materials partially repair defects but cannot fully mimic the biological and mechanical properties of autologous bone. In recent years, hydrogels have become a research hotspot in bone repair due to their excellent biocompatibility and drug-controlled release capabilities. However, precisely regulating the immune microenvironment to accelerate bone healing remains a critical challenge.
This new work developed a novel photothermal-responsive hydrogel (GMHD/TFe@Aca) that significantly enhances bone defect repair by inhibiting the STING signaling pathway and modulating macrophage polarization. The findings were published in Nano Research. The team incorporated the natural flavonoid Acacetin, a STING inhibitor, into the photothermal-responsive hydrogel. Experiments showed that Acacetin effectively suppresses proinflammatory M1 macrophage polarization while promoting anti-inflammatory M2 macrophage activation, reducing inflammation and accelerating bone tissue regeneration. Additionally, Acacetin inhibits osteoclast differentiation, maintaining bone metabolism balance. The hydrogel has the following advantages:1) Precise Drug Release: The hydrogel controllably releases drugs under near-infrared (NIR) stimulation, enabling targeted local therapy. 2) Superior Mechanical Properties: With high compressive strength (45.63 kPa) and adhesion (12.52 N), it meets the mechanical demands of bone defect repair. 3) Dual Regulatory Effects: Acacetin inhibits the STING pathway, modulates macrophage polarization, and promotes angiogenesis and collagen synthesis, comprehensively accelerating bone repair.
In a mouse cranial defect model, the GMHD/TFe@Aca hydrogel significantly promoted new bone formation. NIR irradiation accelerated drug release, further enhancing repair outcomes. After 8 weeks, the experimental group showed a significantly higher bone volume fraction (BV/TV) than the control group, with no observable thermal damage or toxicity. This technology offers a novel strategy for bone repair, combining immune modulation and regenerative functions, with potential to advance clinical translation.
About the Authors
This study was co-led by Prof. Li Su from Shanghai University, Prof. Yuanqing Gao from Nanjing Medical University, and Prof. Minyu Zhu from The First Affiliated Hospital of Wenzhou Medical University. Masters Dinglei Zhang and Qingqiu Huang, along with Ph.D. candidate Dingjun Xu, served as co-first authors. The research was supported by the National Natural Science Foundation of China (Grant No. 81981340417), Zhejiang Provincial Natural Science Foundation of China (Grant No. LY21H070003), and Basic Research Project of Wenzhou City, China (Grant No. Y20220923).
About Nano Research
Nano Research is a peer-reviewed, open access, international and interdisciplinary research journal, sponsored by Tsinghua University and the Chinese Chemical Society, published by Tsinghua University Press on the platform SciOpen. It publishes original high-quality research and significant review articles on all aspects of nanoscience and nanotechnology, ranging from basic aspects of the science of nanoscale materials to practical applications of such materials. After 18 years of development, it has become one of the most influential academic journals in the nano field. Nano Research has published more than 1,000 papers every year from 2022, with its cumulative count surpassing 7,000 articles. In 2024 InCites Journal Citation Reports, its 2024 IF is 9.0 (8.7, 5 years), and it continues to be the Q1 area among the four subject classifications. Nano Research Award, established by Nano Research together with TUP and Springer Nature in 2013, and Nano Research Young Innovators (NR45) Awards, established by Nano Research in 2018, have become international academic awards with global influence.