Combined nucleus pulposus and annulus fibrosus bioactive scaffolds enhance intervertebral disc defect regeneration

Abstract

Combined repair of nucleus pulposus (NP) and annulus fibrosus (AF) is an effective treatment method after discectomy. Tissue engineering techniques for the treatment of discectomy defects typically employ the use of hydrogels. However, this poses challenges due to inadequate mechanical properties and the inability to restore the natural cross-lamellar structure of the AF. Here, we utilized a blend of 3 %(w/v) gelatin methacryloyl (GelMA) hydrogel and biomimetic polycaprolactone (PCL) scaffolds loaded with transforming growth factor β1 (TGF-β1) to repair trapezoidal defects in the AF. The biomimetic PCL microfiber scaffolds significantly improved the compressive strength of the GelMA hydrogel. Additionally, we employed 5 %(w/v) GelMA hydrogel delivered with growth differentiation factor 5 (GDF5) to restore the hydration of the NP following discectomy. The addition of GDF5 and TGF-β1 to the GelMA hydrogel effectively induced stem cell differentiation into NP and AF, respectively. This combined reparative strategy demonstrated favorable outcomes in ovine lumbar spine defects. Magnetic Resonance Imaging (MRI) taken at 1 and 3 months revealed the restoration of NP hydration, while histological staining indicated increased extracellular matrix deposition and preservation of intervertebral disc (IVD) integrity. Our combined treatment strategy offers a promising avenue for achieving endogenous regeneration of IVD following discectomy.