Dextran sulfate-containing thermosensitive hydrogel improves tendon healing by modulating macrophage polarization

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Orthopedic Surgery

Background:

• Tendon rupture healing is hindered by low cell activity and post-injury inflammation.
• Current treatments face challenges in promoting effective tendon regeneration.

Purpose of the Study:

• To develop and evaluate a thermosensitive Pluronic-dextran sulfate (PDS) hydrogel for enhanced tendon repair.
• To assess the hydrogel's ability to modulate macrophage phenotypes and promote extracellular matrix deposition.
• To investigate the hydrogel's impact on tenocyte behavior and inflammatory markers.

Main Methods:

• Fabrication and characterization of a thermosensitive PDS hydrogel with a 13°C phase transition.
• In vitro assessment of hydrogel cytotoxicity, tenocyte proliferation, and migration.
• In vitro gene expression analysis of macrophage markers (M2, IL-1β) and anti-inflammatory effects.
• In vivo biocompatibility testing and evaluation in a rabbit Achilles tendon repair model.
• Assessment of biomechanical properties (tendon-breaking force) and gene expression in repaired tendons.

Main Results:

• The PDS hydrogel demonstrated thermosensitive solidification at 13°C and complied with ISO-10993 non-cytotoxicity standards.
• In vitro studies showed significant increases in tenocyte proliferation (33%) and migration (408%) with PDS hydrogel.
• PDS hydrogel upregulated anti-inflammatory M2 markers (EGR-2 by 4.1-fold) and reduced IL-1β levels by 75%.
• In vivo studies confirmed material biocompatibility and significantly enhanced tendon-breaking force (179.8 N vs. 52.6 N) in rabbit Achilles tendon repair.
• Mechanical and molecular analyses validated PDS hydrogel's promotion of tendon healing and macrophage modulation.

Conclusions:

• The thermosensitive PDS hydrogel is a biocompatible and effective material for promoting tendon healing.
• PDS hydrogel mitigates inflammation by modulating macrophage polarization towards an M2 phenotype.
• The developed hydrogel significantly enhances tenocyte activity and improves biomechanical properties of repaired tendons, showing potential for clinical application.