Gelatin methacrylate hydrogel loaded with brain-derived neurotrophic factor enhances small molecule-induced neurogenic differentiation of stem cells from apical papilla.

The limited neurogenic potential of adult stem cells and their non-specific lineage differentiation pose major challenges in cell-replacement therapy for neurological disorders. In our previous study, we demonstrated that the neurogenic potential of stem cells from apical papilla (SCAPs) was significantly improved upon induction with a small molecule cocktail. This study attempted to investigate whether neuronal differentiation of SCAPs induced by a small molecule cocktail can be further enhanced in a three-dimensional gelatin methacrylate hydrogel loaded with brain-derived neurotrophic factor (BDNF-GelMA). The physiological properties and neural differentiation of SCAPs treated with a combination of small molecules and BDNF-GelMA were evaluated by CCK8, Live/Dead assay, quantitative reverse transcription-polymerase chain reaction, western blot and immunocytochemistry. SCAPs embedded in BDNF-GelMA displayed superior morphological characteristics when induced by a small molecule cocktail, similar to neuronal phenotypes as compared to pure GelMA. There was significant upregulation of neural markers including Tuj1 and MAP2 by SCAPs embedded in BDNF-GelMA, as compared to pure GelMA. Hence, GelMA hydrogel loaded with a potent neurotrophic factor (BDNF) provides a conducive scaffold that can further enhance the differentiation of small molecule-treated SCAPs into neuronal-like cells, which may provide a therapeutic platform for the management of neurological disorders.