Inorganic Ion Eluting Nanoparticulate Mineralized Collagen Glycosaminoglycan Materials (UCLA Case No. 2023-140)

UCLA researchers from the Division of Plastic and Reconstructive Surgery at the UCLA David Geffen School of Medicine have developed an innovative inorganic ion-eluting nanoparticulate mineralized collagen glycosaminoglycan (MC-GAG) material designed for advanced tissue regeneration, particularly bone repair.

INNOVATION: UCLA researchers led by Professor Justine Lee have developed next-generation biomaterial that innovatively couples nanoparticulate mineral release with biologically active collagen glycosaminoglycan scaffolds to optimize bone healing via a synergistic osteogenic and anti-resorptive mechanism. The focus of this innovation is a biocompatible scaffold combining mineralized collagen with glycosaminoglycan, augmented by nanoscale mineral particles capable of releasing inorganic ions such as calcium and phosphate. These ions are critical signaling molecules that modulate cellular behavior in the bone remodeling microenvironment. The inventive scaffold balances promotion of bone formation and suppression of bone resorption through molecular signaling pathways modulated by released inorganic ions, making it a promising candidate for orthopedic, craniofacial, and dental tissue engineering applications.

ADVANTAGES:

• Ion-eluting capability: The scaffold releases calcium and phosphate ions in a controlled manner, which promotes osteogenic differentiation of mesenchymal stem cells (MSCs) and enhances bone tissue regeneration.
• Dual biological action: Beyond stimulating bone-forming cells, the material also inhibits osteoclast activity, thereby reducing bone resorption. This dual effect is achieved both directly by mineral ions and indirectly by promoting secretion of osteoprotegerin (OPG), a natural inhibitor of osteoclasts, from MSCs interacting with the scaffold.
• Nanoparticulate mineralization: The nanoscale mineral phase mimics natural bone extracellular matrix more closely than conventional materials, enabling better integration and cell signaling.
• Growth factor independence: Unlike some regeneration methods, this scaffold operates without the need for exogenous growth factors, simplifying regulatory approval and reducing risks associated with biologics.

DEVELOPMENT TO DATE:

• Demonstrated efficient bone regeneration in preclinical models, including enhanced skull defect repair, with improved biomechanical properties such as hardness and resistance to microfracture.

RELATED PUBLICATIONS (by the inventors only): Ren X, Dejam D, Oberoi MK, Dahan NJ, Zhou Q, Huang KX, Bedar M, Chan CH, Kolliopoulos V, Dewey MJ, Harley BAC, Lee JC. Osteoprotegerin-eluting nanoparticulate mineralized collagen scaffolds improve skull regeneration. Biomater Adv. 2023 Feb;145:213262. doi: 10.1016/j.bioadv.2022.213262. Epub 2022 Dec 20. PMID: 36565669; PMCID: PMC10089592.