Optimizing rhBMP-2 Therapy for Bone Regeneration: From Safety Concerns to Biomaterial-Guided Delivery Systems.

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Orthopedic Surgery

Background:

• Large hard tissue defects pose significant clinical challenges, with autografts and allografts having limitations in availability and compatibility.
• Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a potent osteoinductive factor but its clinical use is limited by dose-dependent complications.
• Conventional collagen carriers lead to rapid release and adverse outcomes, necessitating improved delivery strategies.

Purpose of the Study:

• To review the safety profile of rhBMP-2 and explore strategies for enhancing its therapeutic index.
• To examine advanced biomaterial platforms and molecular delivery approaches for controlled rhBMP-2 release.
• To outline a framework for optimizing rhBMP-2-based regenerative protocols for complex hard tissue defects.

Main Methods:

• Synthesis of preclinical and clinical data on rhBMP-2 safety and efficacy.
• Evaluation of advanced biomaterial carriers (composites, hydrogels, 3D scaffolds) for controlled release.
• Assessment of molecular delivery methods (cmRNA, gene therapy) for site-specific rhBMP-2 expression.

Main Results:

• Low doses of rhBMP-2 (0.5-1.0 mg/level) offer an optimal balance of efficacy and safety.
• Advanced biomaterials enable controlled spatial and temporal release, maintaining osteogenic efficacy.
• Molecular delivery approaches reduce dosing and systemic exposure by providing transient, site-specific expression.

Conclusions:

• Optimizing rhBMP-2 delivery through advanced biomaterials and molecular approaches is crucial for safe and effective bone regeneration.
• Lower rhBMP-2 doses are recommended to balance efficacy and minimize adverse effects.
• Integrating these strategies into multidisciplinary approaches holds significant potential for reconstructing complex hard tissue defects.