Blood-Coagulation-Inspired Dual-Network Hydrogel with Delayed In Situ Gelation for Enhancing Intradiscal Diffusion...

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Biomedical Engineering

Background:

• Intervertebral disc degeneration (IVDD) is a major cause of chronic low back pain.
• Current injectable hydrogels face challenges with diffusion and in situ gelation in the nucleus pulposus.
• Developing effective hydrogels for minimally invasive IVDD treatment is crucial.

Purpose of the Study:

• To develop a novel dual-network hydrogel (HAD-HPTC) inspired by blood coagulation for IVDD treatment.
• To achieve time-programmed diffusion and delayed in situ gelation for enhanced hydrogel delivery and retention.
• To evaluate the therapeutic efficacy of HAD-HPTC in preclinical models of IVDD.

Main Methods:

• Fabrication of a biomimetic dual-network hydrogel with physical and chemical crosslinking networks.
• Utilizing hyaluronic acid-phenylboronic acid (HA-PBA) and tannic acid-cerium metal polyphenol networks (TA-Ce MPNs) for initial diffusion.
• Employing thiol-Michael addition between hyaluronic acid acrylate (HA-AA) and dithiothreitol (DTT) for delayed gelation.
• Incorporating antioxidant, anti-inflammatory, and anti-senescence properties via TA-Ce MPNs.
• Assessing hydrogel performance in rat and rabbit models of IVDD.

Main Results:

• The HAD-HPTC hydrogel demonstrated fluid-like diffusion and conformal filling upon injection.
• Delayed in situ gelation was achieved through the formation of a secondary chemical network.
• Integrated TA-Ce MPNs provided antioxidant, anti-inflammatory, and anti-senescence effects.
• In vivo studies showed superior disc height preservation, extracellular matrix restoration, and inflammation suppression compared to controls.
• The hydrogel promoted effective intervertebral disc regeneration.

Conclusions:

• Blood coagulation-inspired, time-programmed hydrogels represent a promising platform for IVDD treatment.
• The dual-network structure enhances hydrogel delivery, retention, and therapeutic efficacy.
• HAD-HPTC offers a potential minimally invasive strategy for intervertebral disc regeneration and alleviating chronic low back pain.