A One-Stone-Two-Birds Strategy for Intervertebral Disc Repair: Constructing a Reductive Chelation Hydrogel to...

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Biochemistry

Background:

• Intervertebral disc degeneration (IVDD) involves nucleus pulposus (NP) cell fibrosis and extracellular matrix (ECM) breakdown.
• Bioactive hydrogels offer potential for regulating cellular functions and tissue homeostasis in IVDD.
• Current treatments for IVDD face limitations in addressing the complex cellular and matrix pathology.

Purpose of the Study:

• To design and evaluate a dynamic hydrogel (HA-NCSN/Cu) for treating intervertebral disc degeneration (IVDD).
• To investigate the hydrogel's ability to mitigate inflammation and promote ECM regeneration in NP cells.
• To assess the therapeutic efficacy of the hydrogel combined with photothermal therapy in an IVDD model.

Main Methods:

• A dynamic hydrogel (HA-NCSN/Cu) was synthesized using hyaluronic acid grafted with thiourea (HA-NCSN) and Cu2+.
• The hydrogel's photothermal properties and reactive oxygen species (ROS) scavenging capabilities were characterized.
• RNA sequencing was employed to analyze cellular pathway alterations, and in vitro/in vivo experiments were conducted to evaluate therapeutic effects.

Main Results:

• The HA-NCSN/Cu hydrogel exhibited a rapid photothermal effect and effectively scavenged ROS, reducing NP cell inflammatory stress.
• Glutathione signaling pathways were significantly altered, and mild photothermal therapy activated the TGF-β/Smad pathway.
• This promoted the expression of Aggrecan and Collagen II, leading to ECM regeneration and restoration of disc structure and function in vivo.

Conclusions:

• The dynamic HA-NCSN/Cu hydrogel demonstrates significant potential for treating IVDD by modulating inflammation and enhancing matrix regeneration.
• The combination of ROS scavenging and photothermal therapy offers a promising strategy for IVDD treatment.
• This bioactive hydrogel represents a viable therapeutic candidate for restoring damaged intervertebral disc function.