Layer-by-layer self-assembly polyelectrolytes loaded with cyclic adenosine monophosphate enhances the osteo/odontogenic differentiation of stem cells from apical papilla

J Biomed Mater Res A. 2021 Feb;109(2):207-218. doi: 10.1002/jbm.a.37017. Epub 2020 Jul 9.

Abstract

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.

Keywords: cell encapsulation; layer-by-layer; self-assembly; stem cell; tissue engineering.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alginates / chemistry
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cyclic AMP / chemistry*
  • Cyclic AMP Response Element-Binding Protein / chemistry
  • Dental Papilla / cytology
  • Dental Papilla / drug effects*
  • Gelatin / chemistry
  • Humans
  • Odontogenesis / drug effects*
  • Odontogenesis / genetics
  • Osteogenesis / drug effects*
  • Osteogenesis / genetics
  • Polyelectrolytes / chemistry*
  • RNA, Messenger / biosynthesis
  • Stem Cells / drug effects*
  • Up-Regulation / drug effects
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Alginates
  • Cyclic AMP Response Element-Binding Protein
  • Polyelectrolytes
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • Gelatin
  • Cyclic AMP