RANKL delivery from calcium phosphate containing PLGA microspheres

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Orthopedic Research

Background:

• Bone substitute materials should ideally degrade and be replaced by new bone.
• Receptor Activator of Nuclear factor Kappa-B Ligand (RANKL) stimulates osteoclast formation, crucial for bone remodeling.

Purpose of the Study:

• To investigate methods for loading RANKL into injectable calcium phosphate cement (CPC).
• To evaluate the effect of loading methods on RANKL release and biological activity.

Main Methods:

• RANKL was loaded onto or incorporated into poly(lactic-co-glycolic acid) (PLGA) microspheres (hollow and dense).
• Microspheres were embedded in CPC; controls included non-embedded microspheres and RANKL adsorbed onto plain CPC.
• RANKL release (RP-HPLC) and osteoclast-like cell formation were assessed.

Main Results:

• Sustained release of active RANKL was achieved when adsorbed onto PLGA microspheres.
• Inactive RANKL was released from CPC-PLGA formulations with incorporated RANKL or RANKL in the CPC liquid phase.
• Effective RANKL loading in injectable CPC requires adsorption to PLGA microspheres.

Conclusions:

• Adsorption to PLGA microspheres is the optimal method for loading RANKL into injectable CPC.
• This approach enables sustained release of active RANKL for potential bone regeneration applications.