ArticleDrug design, development and therapy2026
Tideglusib-Preactivated Osteoblasts Encapsulated in Ceramic Particle-Reinforced GelMA Hydrogel for Enhanced Critical-Size Bone Defect Regeneration.
Article in Drug design, development and therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Purpose: Critical-size bone defects remain a clinical challenge due to limited intrinsic bone regeneration. This study developed a composite scaffold composed of osteoinductive biphasic calcium phosphate (BCP) ceramic particles and gelatin methacryloyl (GelMA) hydrogel, loaded with calvarial osteoblasts (OBs) pretreated with the glycogen synthase kinase-3β (GSK-3β) inhibitor Tideglusib on surface of BCP particles, and evaluated its bone regenerative efficacy. Methods: BCP particles were characterized by X-ray diffraction and scanning electron microscopy. GelMA was synthesized and characterized by FTIR and Results: BCP (200-300 μm, HA/β-TCP ~30:70) incorporation enhanced GelMA compressive modulus ~4-fold. In vitro, 1 μM Tideglusib optimally activated Wnt/β-catenin signaling and promoted OB proliferation, migration, and osteogenic differentiation, with sustained effects after drug removal. OBs on BCP particles showed time-dependent upregulation of osteogenic genes, and Tideglusib pretreatment further elevated this expression. In vivo, micro-CT revealed significantly higher BV/TV, Tb.N, Tb.Th, and BMD in the GPCT group versus others. Histology showed more mature bone with numerous osteocytes, partial degradation of BCP particles, and new bone area fraction >70% in GPCT. Conclusion: The composite BCP particle/GelMA scaffold with Tideglusib-pretreated OBs provides mechanical reinforcement and sustained osteogenic stimulation, effectively accelerating critical-size bone defect regeneration. This ex vivo pharmacological priming strategy represents a promising translational approach for bone tissue engineering.
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