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

Abstract 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.