Hydrogel microarchitecture as a regulatory cue for in vitro odontogenic differentiation

Abstract

Objective: This study introduces an innovative, cost-effective, and easily reproducible strategy for engineering three-dimensional bioprinted GelMA-based scaffolds, designed with ordered macroporous and tubular architectures, and integrated microfluidic channels to advance structural and functional performance. Their geometric features were specifically designed to investigate how microarchitectural cues influence the mineralizing cell differentiation of human dental pulp cells (HDPCs). Methodology: The scaffolds were fabricated via an indirect bioprinting process using resin molds, resulting in cylindrical structures with distinct grid or honeycomb surface architectures. Biomaterials were characterized for morphology, surface topography, porosity, pore diameter, and degradability. Biological performance was evaluated by culturing HDPCs for 21 days to assess viability, proliferation, and mineralizing differentiation (ANOVA/Tukey; α=0.05). Results: Both scaffold designs exhibited interconnected porous networks, with the honeycomb configuration presenting significantly larger pores. HDPCs cultured on the scaffolds showed high viability and proliferation, with the honeycomb architecture promoting elevated ALP activity. However, the grid architecture more effectively influenced odontoblastic differentiation and mineralized matrix deposition. Conclusion: Our findings highlight the impact of biomaterial architecture on cellular behavior and reveal the potential of this novel bioprinting approach for bioactive dentin regeneration in dental tissue engineering.