Active\nMagnesium Boride/Alginate Hydrogels Rejuvenate\nSenescent Cells

The\nclearance of senescent cells may be detrimental to low cell\ndensity diseases, such as intervertebral disc degeneration (IVDD),\nand rejuvenating these cells presents a formidable obstacle. In this\nstudy, we investigate a mild-alkalization strategy employing magnesium\nboride-alginate (MB-ALG) hydrogels to rejuvenate senescent cells associated\nwith age-related diseases. MB-ALG hydrogels proficiently ensnare senescent\ncells owing to their surface roughness. The hydrolysis of MB-ALG hydrogels\nliberates hydroxide ions (OH<sup>–</sup>), effecting a transition\nfrom an acidic microenvironment (pH ∼ 6.2) to a mildly alkaline\nstate (pH ∼ 8.0), thereby fostering senescent cell proliferation\nvia activation of the PI3K/Akt/mTOR pathway. Additionally, H<sub>2</sub> aids in ROS clearance, which reduces cellular oxidative stress.\nAnd, Mg<sup>2+</sup> rejuvenates senescent cells by inhibiting Ca<sup>2+</sup> influx and fine-tuning the sirt1-p53 signaling pathways.\nBoth <i>in vitro</i> and <i>in vivo</i> experiments\nconducted on rat intervertebral discs corroborate the sustained antisenescence\nand rejuvenation properties of MB-ALG hydrogels, with effects persisting\nfor up to 12 weeks postoperation. These discoveries elucidate the\nrole of mild-alkalization in dictating cellular destiny and provide\nkey insights for addressing age-related diseases.