In situ spermidine-integrated dynamic hyaluronic acid-based hydrogels platforms for anti-inflammation and...

Area of Science:

• Biomaterials Science
• Ophthalmology
• Regenerative Medicine

Background:

• Subconjunctival injuries cause vision impairment via inflammation and fibrosis.
• Current treatments lack efficient drug delivery and responsiveness to dynamic healing processes.
• There is a critical need for safe treatments with dual anti-inflammatory and anti-fibrotic effects.

Purpose of the Study:

• To develop an innovative dual-crosslinked hyaluronic acid-based dynamic hydrogel for subconjunctival injury management.
• To utilize the hydrogel as a carrier for sustained release of spermidine (SPD).
• To evaluate the hydrogel's anti-inflammatory and anti-fibrotic therapeutic potential in vivo.

Main Methods:

• Fabrication of a dual-crosslinked hyaluronic acid hydrogel capable of immobilizing and releasing spermidine via dynamic bonds.
• Assessment of hydrogel properties including injectability, self-healing, and sustained release.
• In vivo evaluation of the hydrogel-SPD system in a subconjunctival injury model to analyze inflammatory and fibrotic markers.

Main Results:

• The engineered hydrogel exhibited injectability, self-healing, and controlled, sustained spermidine release.
• The system demonstrated synergistic anti-inflammatory and antioxidant effects.
• In vivo studies showed significant reduction in pro-inflammatory signaling and suppression of fibrotic progression by modulating collagen deposition.

Conclusions:

• This dual-crosslinked hyaluronic acid-based dynamic hydrogel serves as an effective carrier for spermidine delivery.
• The developed therapeutic system offers a promising approach for managing subconjunctival injuries by mitigating inflammation and fibrosis.
• This work provides a foundation for treating various ocular surface fibrotic diseases.