Injectable Hybrid Hydrogel Loaded with circFADS1 Microspheres for the Differentiation of Nucleus Pulposus...

Intervertebral disc degenerative disease is a major contributor to chronic low back pain and has a profound impact on patients' quality of life. Nucleus pulposus tissue-derived stem cells (NPSCs) hold considerable promise for intervertebral disc repair due to their capacity for self-renewal and multipotent differentiation. However, challenges such as low survival rates and inefficient differentiation hinder their regenerative potential and therapeutic effectiveness, necessitating further optimization. In this study, we developed a composite system combining circFADS1-loaded microspheres with a hybrid hydrogel (HH) scaffold. This system provides a three-dimensional matrix and a bioactive microenvironment designed to enhance the differentiation capacity of NPSCs and facilitate intervertebral disc tissue repair. In vitro results demonstrated that the composite hydrogel supports NPSC growth and significantly improves their chondrogenic differentiation. Animal studies validated the system's ability to partially promote nucleus pulposus regeneration. This study presents a novel approach for tissue engineering-based treatments of degenerative disc disease.