Hydrogen Ion Capturing Hydrogel Microspheres for Reversing Inflammaging

Inflammaging is deeply involved in aging-related diseases and can be destructive during aging. The maintenance of pH balance in the extracellular microenvironment can alleviate inflammaging and repair aging-related tissue damage. In this study, the hydrogen ion capturing hydrogel microsphere (GMNP) composed of mineralized transforming growth factor-beta (TGF-beta) and catalase (CAT) nanoparticles is developed via biomimetic mineralization and microfluidic technology for blocking the NLRP3 cascade axis in inflammaging. This GMNP can neutralize the acidic microenvironment by capturing excess hydrogen ions through the calcium carbonate mineralization layer. Then, the subsequent release of encapsulated TGF-beta and CAT can eliminate both endogenous and exogenous stimulus of NLRP3, thus suppressing the excessive activation of inflammaging. In vitro, GMNP can suppress the excessive activation of the TXNIP/NLRP3/IL-1 beta cascade axis and enhance extracellular matrix (ECM) synthesis in nucleus pulposus cells. In vivo, GMNP becomes a sustainable and stable niche with microspheres as the core to inhibit inflammaging and promote the regeneration of degenerated intervertebral discs. Therefore, this hydrogen ion-capturing hydrogel microsphere effectively reverses inflammaging by interfering with the excessive activation of NLRP3 in the degenerated tissues. Lactic acid produced in degenerated tissues can activate the NLRP3/Caspase-1/IL-1 beta axis and cause chronic inflammation, finally restricting tissue restoration. The engineered hydrogen ion-capturing hydrogel microspheres (GMNP) using biomimetic mineralization and microfluidic technologies can block the NLRP3 axis by simultaneously capturing excess hydrogen ions and suppressing mitochondrial reactive oxygen species (ROS), eventually reconstructing the tissue microenvironment and promoting tissue regeneration.image