Nanogel Integrated Zwitterionic Injectable Hydrogel with Sequential Drug-Releasing Capability for the Programmable...

Area of Science:

• Biomaterials Science
• Neuroscience
• Regenerative Medicine

Background:

• Spinal cord injury (SCI) is a severe neurological condition with complex pathogenesis.
• Existing drug delivery systems for SCI lack precise control over drug release.
• There is a need for advanced therapeutic strategies to manage SCI's acute and subacute phases.

Purpose of the Study:

• To design an integrative hydrogel system for controlled, sequential drug delivery after SCI.
• To investigate the therapeutic effects of melatonin and ibuprofen released sequentially from the hydrogel.
• To evaluate the hydrogel's potential for repairing spinal cord injury.

Main Methods:

• Development of a novel hydrogel system (Dex/Per-g-PSB) cross-linked with dendritic macromolecular nanogels (Per-g-PSB).
• Incorporation of melatonin (Mel) and ibuprofen (Ibu) into the hydrogel platform (Mel/Ibu@D/P-g-PSB) for sequential release.
• Assessment of drug release mechanisms (diffusion and electrostatic interactions) and their impact on SCI in preclinical models.

Main Results:

• The hydrogel platform achieved sequential release of melatonin and ibuprofen.
• Melatonin exhibited neuroprotective effects in the acute phase by downregulating inflammatory cytokines.
• Ibuprofen reduced RhoA signaling activation by blocking the ROCK pathway in the subacute phase, mitigating secondary damage.

Conclusions:

• The ion-sensitive hydrogel platform enables controlled, sequential drug delivery for SCI.
• The combined anti-inflammatory and ROCK pathway-blocking effects promote significant spinal cord repair.
• This innovative approach offers a promising therapeutic strategy for managing spinal cord injuries.