Bone defects caused by trauma, infection, tumors, or osteoporosis pose significant clinical challenges, especially with rising fracture incidence in aging populations. The regulation of immune microenvironment in bone defect lesions by drug-loaded hydrogel has been shown to accelerate bone healing. In this study, we developed a photothermal-responsive hydrogel (GMHD/TFe@Aca) loaded with acacetin, a natural flavonoid with anti-inflammatory and immunomodulatory properties. The hydrogel loaded with TFe@Aca nanoparticles exhibited excellent mechanical properties, biocompatibility, and low cytotoxicity. In a mouse model of bone defect, this photothermal-responsive hydrogel facilitated sustained drug release at the bone defect site, with the drug release rate controlled through light stimulation. Acacetin was found to inhibit stimulator of interferon genes (STING) activation, suppress M1 macrophage polarization, and promote M2 polarization. Near-infrared (NIR)-triggered acacetin release further accelerated bone repair by reducing inflammatory cytokines, promoting collagen synthesis, and enhancing angiogenesis. These findings highlight GMHD/TFe@Aca as a multifunctional material capable of modulating inflammation and promoting bone regeneration, offering a promising strategy for bone defect treatment and advancing biomaterial development in regenerative medicine.

Rhodiola crenulate is the edible medicinal herbal medicine widely used for altitude sickness in China. Interestingly, our previous work has found that R. crenulate extract (RCE) could significantly improve the pathology associated with dextran sulfate sodium-induced colitis. Thus, the current research aims to reveal the pharmacodynamic material basis of RCE, as well as its mechanism against colitis. The chemical characterization of RCE was performed by UHPLC-HR-MS, through which a total of 88 constituents were identified. Meanwhile, our results also found 29 constituents absorbed into blood and 8 metabolized absorbable compounds. The decreased flavonoids prototype and the elevated sulfated products of phenols were observed under pathophysiological conditions of colitis. The metabolomics study revealed that colitis caused the alternation of fatty acid metabolism, steroid hormone biosynthesis and bile acid metabolism. Correspondingly, RCE could prevent colitis by improving fatty acid metabolism and secondary bile acid metabolism.