A Mechanically Matched Hydrogel Incorporated with Biomimetic Mineralized Liposome for Synergistic Nucleus Pulposus Repairment

Intervertebral disc degeneration (IVDD) is recognized as a major cause of back pain, yet the underlying mechanism of degeneration remains unclear. Although hydrogels have been explored to replace the nucleus pulposus (NP) to delay IVDD, mechanical incompatibility may exacerbate the degeneration. Moreover, a single mechanical support cannot effectively address the vicious cycle between damaged NP cells and the pathological microenvironment. To address these challenges, a mineralized liposome inspired by natural diatoms was developed. Liposome loading melatonin (MT) was utilized to mimic the core of diatoms, while the mineralized magnesium pyrophosphate shell incorporated with epigallocatechin gallate (EGCG), which decorated the liposome surface, was utilized to mimic the frustules of diatoms. After that, a mechanically matched hydrogel named PGB was prepared and acted as storage for loading the mineralized liposome. The mineralized layer of the liposome could be rapidly disintegrated in the IVDD acidic microenvironment, and the quickly released magnesium ions (Mg²⁺) could maintain NP cells active while the released EGCG could scavenge reactive oxygen species (ROS) in the NP microenvironment. Meanwhile, the continuously released liposome encapsulated with MT could adjust extracellular matrix (ECM) synthesis after cellular up by NP cells, achieving NP repair by an inside-out cooperation strategy. The hydrogel platform provides insight into the treatment of IVDD.