Polydopamine-Functionalized HMS/PLGA Composite Microsphere Scaffold Modulates Enhances Immunomodulation and Bone...

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Regenerative Medicine

Background:

• Developing poly(lactic-co-glycolic acid) (PLGA)-based scaffolds with osteogenic activity, hydrophilicity, and mechanical strength is challenging.
• Hexagonal mesoporous silica (HMS)/PLGA composite microsphere scaffolds (HP) were previously developed.
• Surface modification is crucial for enhancing scaffold properties.

Purpose of the Study:

• To develop and evaluate a polydopamine (PDA)-modified HMS/PLGA composite microsphere scaffold (PHP) for enhanced bone regeneration.
• To assess the effects of PHP on cell proliferation, osteogenic differentiation, and immune microenvironment modulation.
• To investigate the in vivo efficacy of PHP in a rat calvarial defect model.

Main Methods:

• Fabrication of HP and PDA-modified PHP scaffolds.
• In vitro assessment of scaffold properties (compressive strength, hydrophilicity, porosity).
• In vitro evaluation of bone marrow stromal cell (BMSC) proliferation and osteogenic differentiation.
• In vivo study using a rat calvarial defect model with micro-CT and histological analysis.
• Immunohistochemical analysis of macrophage polarization markers (CD163, iNOS).

Main Results:

• PHP exhibited improved compressive strength and hydrophilicity compared to HP, while maintaining porosity.
• In vitro studies showed PHP promoted BMSC proliferation and osteogenic differentiation, upregulating osteogenic gene expression.
• PHP induced M2 anti-inflammatory macrophage polarization.
• In vivo, PHP significantly enhanced bone regeneration in rat calvarial defects.
• PHP upregulated BMP-2 and VEGF expression, promoting osteogenesis and angiogenesis.
• Immunostaining confirmed M2 polarization (increased CD163, decreased iNOS) in vivo.

Conclusions:

• The ternary composite scaffold (PHP) effectively integrates HMS structural features with PDA surface functionalization.
• PHP demonstrates simultaneous regulation of the immune microenvironment and osteogenesis.
• This scaffold represents a promising strategy for clinically translatable bone repair materials.