Injectable hydrogel loaded with exosomes from hypoxic umbilical cord-derived mesenchymal stem cells alleviates intervertebral disc degeneration by reversing nucleus pulposus cell senescence

Intervertebral disc degeneration is a significant contributor to the development of spinal disorders. Previous studies have shown that the senescence of nucleus pulposus cells can worsen the degradation of intervertebral disks. Therefore, targeting the senescence of nucleus pulposus cells may be a promising therapeutic approach for the treatment of intervertebral disc degeneration. This study investigated the use of exosomes from hypoxic umbilical cord-derived mesenchymal stem cells to reverse nucleus pulposus cells senescence and delay intervertebral disc degeneration progression. MicroRNA sequencing of hypoxic umbilical cord-derived mesenchymal stem cells revealed the presence of functional microRNAs, with the p53 signalling pathway identified as a key factor. To enhance the release time of hypoxic umbilical cord-derived mesenchymal stem cells <i>in vivo</i>, hyaluronic acid methacryloyl hydrogel was used to load hypoxic umbilical cord-derived mesenchymal stem cells and create a sustained-release system. This system effectively repaired the degradation of the extracellular matrix, reversed nucleus pulposus cells senescence and alleviated intervertebral disc degeneration progression in a rat model. Overall, this study highlights the potential of hypoxic umbilical cord-derived mesenchymal stem cells in reducing nucleus pulposus cell senescence and suggests the possibility of combining it with a sustained-release system as a novel therapeutic strategy for intervertebral disc degeneration.