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Cranial Bone Regeneration via Polymerized α-Ketoglutarate Based Biomaterials
Abstract   Peer reviewed

Cranial Bone Regeneration via Polymerized α-Ketoglutarate Based Biomaterials

Jeffrey S. Marschall and Hongli Sun
Journal of oral and maxillofacial surgery, Vol.84(8), pp.e13-e14
08/2026
DOI: 10.1016/j.joms.2026.05.034

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Abstract

Purpose Regeneration of bone in the craniofacial complex is a central focus for our specialty. Biomaterial based tissue engineering presents an alternative strategy to address the challenges posed by autologous reconstruction. The purpose of this investigation was to demonstrate the ability to regenerate cranial bone in a mouse model using a polymerized alpha ketoglutarate micro and nanoparticles. Materials and Methods Novel AKG-based polymeric microparticles and nanoparticles (PAKG MPs and NPs) are synthesized for sustained release. Biochemical and molecular biology techniques were used to characterize the materials. RNA-sequencing, confocal microscopy and in vivo animals studies were utilized to determine the osteogenic potentials of the biomaterials. Results In vitro data suggest that the chemical components, hydrophilicity, and size of the MPs can significantly affect their cytotoxicity and pro-osteogenic activity. Biodegradable PAKG MPs are highly phagocytosable in preosteoblasts MC3T3-E1 and primary bone marrow mesenchymal stem cells, significantly promoting their osteoblastic differentiation. RNA-Sequencing data suggest that PAKG MPs strongly activate Wnt/β-catenin and PI3K–Akt pathways for osteogenic differentiation. PAKG enables poly (L-lactic acid) and poly (lactic-co-glycolic acid) MPs (PLGA MPs) for efficient phagocytosis. PAKG MPs significantly improve large bone regeneration in a mouse cranial bone defect model. Conclusions PAKG-based materials show promise to improve osteogenic differentiation and bone regeneration and enable efficient intracellular drug delivery for cranial bone defects.

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