Active Magnesium Boride/Alginate Hydrogels Rejuvenate Senescent Cells

The clearance of senescent cells may be detrimental to low cell density diseases, such as intervertebral disc degeneration (IVDD), and rejuvenating these cells presents a formidable obstacle. In this study, we investigate a mild-alkalization strategy employing magnesium boride-alginate (MB-ALG) hydrogels to rejuvenate senescent cells associated with age-related diseases. MB-ALG hydrogels proficiently ensnare senescent cells owing to their surface roughness. The hydrolysis of MB-ALG hydrogels liberates hydroxide ions (OH^-), effecting a transition from an acidic microenvironment (pH ∼ 6.2) to a mildly alkaline state (pH ∼ 8.0), thereby fostering senescent cell proliferation via activation of the PI3K/Akt/mTOR pathway. Additionally, H₂ aids in ROS clearance, which reduces cellular oxidative stress. And, Mg²⁺ rejuvenates senescent cells by inhibiting Ca²⁺ influx and fine-tuning the sirt1-p53 signaling pathways. Both <i>in vitro</i> and <i>in vivo</i> experiments conducted on rat intervertebral discs corroborate the sustained antisenescence and rejuvenation properties of MB-ALG hydrogels, with effects persisting for up to 12 weeks postoperation. These discoveries elucidate the role of mild-alkalization in dictating cellular destiny and provide key insights for addressing age-related diseases.