Controlled Release of TGF-β3 for Effective Local Endogenous Repair in IDD Using Rat Model

Abstract

Introduction: Intervertebral disc (IVD) degeneration (IDD) is one of the most widespread musculoskeletal diseases worldwide and remains an intractable clinical challenge. Currently, regenerative strategies based on biomaterials and biological factors to facilitate IVD repair have been widely explored. However, the harsh microenvironment, such as increased ROS and acidity, of the degenerative region impedes the efficiency of IVD repair. Here, an intelligent biodegradable nanoplatform using hollow manganese dioxide (H-MnO₂) was developed to modulate the degenerative microenvironment and release transforming growth factor beta-3 (TGF-β3), which may achieve good long-term therapeutic effects on needle puncture-induced IDD.

Methods: Surface morphology and elemental analysis of the MnO₂ nanoparticles (NPs) were performed by transmission electron microscopy and an energy-dispersive X-ray spectroscopy detector system, respectively. The biological effects of MnO₂ loaded with TGF-β3 (TGF-β3/MnO₂) on nucleus pulposus cells (NPCs) were assessed via cytoskeleton staining, EdU staining, qPCR and immunofluorescence. The efficacy of TGF-β3/MnO₂ on needle puncture-induced IDD was further examined using MRI and histopathological and immunohistochemical staining.

Results: The MnO₂ NPs had a spherical morphology and hollow structure that dissociated in the setting of a low pH and H₂O₂ to release loaded TGF-β3 molecules. In the oxidative stress environment, TGF-β3/MnO₂ was superior to TGF-β3 and MnO₂ NPs in the suppression of H₂O₂-induced matrix degradation, ROS, and apoptosis in NPCs. When injected into the IVDs of a rat IDD model, TGF-β3/MnO₂ was able to prevent the degeneration and promote self-regeneration.

Conclusion: Use of an MnO₂ nanoplatform for biological factors release to regulate the IDD microenvironment and promote endogenous repair may be an effective approach for treating IDD.

Keywords: endogenous repair; hollow manganese dioxide; intervertebral disc degeneration; oxidative stress; transforming growth factor beta-3.