Dexamethasone Long-Term Controlled Release from Injectable Dual-Network Hydrogels with Porous Microspheres...

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Regenerative Medicine

Background:

• Developing injectable, long-lasting platforms for bone regeneration remains a challenge.
• Existing methods lack controlled drug release and optimal immune modulation for bone healing.

Purpose of the Study:

• To create an injectable, controlled-release hydrogel platform for enhanced bone regeneration.
• To investigate the osteogenic and immunomodulatory effects of drug-loaded microspheres within a dual-network hydrogel.

Main Methods:

• Synthesized porous dexamethasone/hexagonal mesoporous silica/poly(lactic-co-glycolic acid) microspheres (PDHP).
• Formulated an injectable photocurable dual-network hydrogel using methacrylated silk (SilMA) and sodium alginate (SA) loaded with PDHP.
• Evaluated in vitro drug release kinetics, biocompatibility, and osteogenic effects.
• Assessed in vivo bone regeneration in cranial defects of Sprague-Dawley rats.

Main Results:

• PDHP demonstrated superior promotion of bone mesenchymal stem cell proliferation and osteogenic differentiation compared to controls.
• The PDHP-loaded hydrogel provided sustained drug release for over 4 months and achieved zero-order release in vitro for 48 days.
• A 1% microsphere concentration in the hydrogel significantly enhanced osteogenic gene expression (BMP-2, OPN) and M2 macrophage polarization.
• In vivo studies showed the PDHP/SS hydrogel effectively promoted cranial bone defect healing, angiogenesis, and M2 macrophage polarization while suppressing M1 macrophages.

Conclusions:

• The developed injectable hydrogel platform with drug-loaded microspheres offers a promising solution for long-term, controlled drug delivery in bone tissue engineering.
• The platform's ability to modulate the immune microenvironment and promote angiogenesis contributes to effective in situ bone healing.
• This advanced hydrogel system holds significant potential for clinical applications in treating bone defects and abnormalities.