Cyclic adenosine monophosphate (cAMP) is a second messenger involved in the 
dental regeneration. However, efficient long-lasting delivery of cAMP that is 
sufficient to mimic the in vivo microenvironment remains a major challenge. 
Here, cAMP was loaded in stem cells from apical papilla (SCAPs) using 
layer-by-layer self-assembly with gelatin and alginate polyelectrolytes 
(LBL-cAMP-SCAPs). LBL-cAMP-SCAPs expressed cAMP and increased the 
phosphorylation level of cAMP-response element-binding protein (CREB) which were 
evaluated by immunofluorescence and western blotting (WB). Enzyme-linked 
immunosorbent assay (ELISA) demonstrated that a sustained release of cAMP and 
vascular endothelial growth factor (VEGF) were present up to 14 days. Scanning 
electron microscopy (SEM) found LBL-coated SCAPs exhibited a spheroid-like 
morphology. CCK8 and live/dead staining showed that LBL treatment had no 
significant effect on cell proliferation and viability. LBL-cAMP-SCAPs enhanced 
mineralized nodule formation and up-regulated the mRNA levels of the 
osteogenesis-related genes, as well as related transcription factor-2 protein 
level which were revealed by Alizarin red staining, RT-PCR and WB, respectively. 
In conclusion, LBL self-assembly loaded with cAMP promoted the osteo/odontogenic 
differentiation of SCAPs, thereby providing a potential strategy for bioactive 
molecular delivery in dental regeneration.