Injectable Multifunctional Drug Delivery System for Hard Tissue Regeneration under Inflammatory Microenvironments

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Tissue Engineering

Background:

• Developing effective strategies for hard tissue regeneration requires advanced hydrogel systems.
• These systems should amplify progenitor cell regeneration by delivering therapeutics during inflammation.

Purpose of the Study:

• To engineer an injectable, multifunctional drug delivery system for hard tissue regeneration.
• To investigate the potential of dexamethasone (DEX)-loaded halloysite clay nanotubes (HNTs) within a gelatin methacryloyl (GelMA) hydrogel for bone regeneration under inflammatory conditions.

Main Methods:

• Engineered injectable GelMA hydrogels incorporating DEX-loaded HNTs.
• Analyzed hydrogel physicochemical properties, mechanical strength, and DEX release kinetics.
• Evaluated cytocompatibility with human exfoliated deciduous teeth-derived mesenchymal stem cells (SHEDs).
• Assessed anti-inflammatory effects and mineralization potential both in vitro and in vivo.

Main Results:

• DEX-loaded HNTs enhanced GelMA hydrogel mechanical strength without altering degradation or swelling.
• GelMA formulations with HNTs/DEX showed excellent cytocompatibility with SHEDs.
• Optimal osteogenic differentiation of SHEDs was observed with 10% HNT/DEX incorporation.
• In vitro studies demonstrated DEX-controlled release promoted mineralization and counteracted inflammation in LPS-stimulated SHEDs.
• In vivo experiments showed significantly enhanced bone formation with DEX-loaded nanotube-modified GelMA compared to controls.

Conclusions:

• Engineered DEX-loaded HNT-modified GelMA hydrogels represent a promising injectable system for hard tissue regeneration.
• This approach effectively promotes progenitor cell differentiation and bone formation, even in inflammatory environments.
• The developed hydrogel system shows significant potential for clinical translation in regenerative medicine.