Injectable PLGA microspheres with tunable magnesium ion release for promoting bone regeneration

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Orthopedic Engineering

Background:

• Magnesium ions (Mg²⁺) are crucial for bone tissue regeneration, but their effectiveness depends on concentration.
• Existing bone tissue engineering scaffolds lack precise control over Mg²⁺ release.
• Biodegradable microspheres offer a promising platform for controlled delivery of bioactive factors.

Purpose of the Study:

• To develop injectable, biodegradable microspheres for controlled Mg²⁺ release.
• To investigate the impact of varying MgO/MgCO₃ ratios on Mg²⁺ release kinetics.
• To evaluate the efficacy of these microspheres in promoting bone regeneration in vitro and in vivo.

Main Methods:

• Lactone-based biodegradable microspheres (PMg) were fabricated from poly(lactide-co-glycolide) (PLGA) co-embedded with MgO and MgCO₃ in different ratios.
• Mg²⁺ release profiles were analyzed based on MgO/MgCO₃ weight ratios.
• In vitro studies assessed microsphere cytotoxicity, bone marrow mesenchymal stromal cell (BMSC) attachment, proliferation, migration, and osteogenic differentiation.
• In vivo studies utilized a rat calvarial defect model to evaluate bone regeneration.

Main Results:

• PMg microspheres demonstrated tunable Mg²⁺ release; higher MgO fractions yielded faster release, while higher MgCO₃ fractions provided sustained release.
• All PMg microspheres were non-cytotoxic and promoted BMSC attachment, proliferation, migration, and osteogenic differentiation.
• PMg-III microspheres (1:1 MgO/MgCO₃ ratio) showed the strongest osteogenic potential in vitro.
• In vivo, PMg-III microspheres significantly enhanced bone regeneration in calvarial defects, increasing bone volume fraction (BV/TV) and bone mineral density (BMD) compared to controls.

Conclusions:

• Biodegradable microspheres can be engineered for precise, tunable Mg²⁺ release.
• Controlled Mg²⁺ release from PMg microspheres effectively promotes bone regeneration.
• This strategy offers a promising approach for developing advanced bone tissue engineering scaffolds for clinical applications.