Photothermal-triggered NO-releasing nanofiber membrane mitigates intervertebral disc degeneration via inflammation inhibition and matrix stabilization

Intervertebral disc-related low back pain represents a major source of chronic pain. Due to the inflammatory microenvironment and impaired extracellular matrix (ECM) synthesis in intervertebral disc degeneration (IVDD), annulus fibrosus (AF) injuries have limited healing capacity. Effective AF repair thus requires modulation of the inflammatory state, promotion of ECM deposition, and enhancement of cellular migration. In this study, we developed a multifunctional photothermal nanofibrous membrane system by electrospinning biocompatible chitosan (CS) and polyvinyl alcohol (PVA) integrated with the photosensitizer polyaniline (PANI) and the nitric oxide (NO) donor S-nitrosoglutathione (GSNO). The system enables mild photothermal therapy (MPTT)-NO synergy via NIR-triggered photothermal heating and controlled NO release. Under NIR irradiation, the generated mild heat induces AF cells to upregulate heat shock proteins (HSPs), thereby enhancing tissue repair. Furthermore, leveraging the thermosensitive release of NO from GSNO, PVA-CS-PANI-GSNO achieves spatiotemporal NO delivery under NIR control, which acts synergistically with MPTT to suppress inflammatory cytokine expression, promote ECM remodeling, and inhibit apoptosis of AF cells, ultimately facilitates the repair of the AF. By overcoming the limitations of systemic anti-inflammatory therapies imposed by the avascular nature of the AF, this strategy offers a promising avenue for the treatment of AF injuries associated with IVDD.