Simvastatin and nanofibrous poly(l-lactic acid) scaffolds to promote the odontogenic potential of dental pulp cells in an inflammatory environment

Abstract

The regeneration potential of stem cells is dependent on their microenvironment. In this study, we investigated the effect of the microenvironment of dental pulp stem cells (DPSCs), including 3D structure of a macroporous and nanofibrous scaffold, the inflammatory stimulus lipopolysaccharide (LPS) and a biological molecule simvastatin, on their regenerative potential of mineralized dentin tissue. The results demonstrated that LPS upregulated inflammatory mediators and suppressed the odontogenic potential of DPSCs. Known as a lipid-lowing agent, simvastatin was excitingly found to repress the expression of pro-inflammatory mediators, up-regulate odontoblastic markers, and exert a pro-angiogenic effect on endothelial cells, resulting in enhanced vascularization and mineralized dentin tissue regeneration in a biomimetic 3D tissue engineering scaffold. This novel finding is significant for the fields of stem cells, inflammation and dental tissue regeneration.

Simvastatin Induces In Vitro Mineralization Effects of Primary Human Odontoblast-Like Cells

“…This corresponds well with the SV concentrations used in other studies (0.01, 0.1, 1 and 10 µM) investigating human odontoblast-like and dental pulp stem cells [ 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ]. The mentioned studies examined different parameters of human cells, for instance expression levels of ALP-conversion rates and dentin matrix acidic phosphoprotein 1 (DMP-1) [ 29 , 30 , 31 , 35 , 36 ], dentin sialophosphoprotein (DSPP) [ 29 , 32 , 34 , 35 , 36 , 37 , 39 ], bone morphogenic protein 2 (BMP-2) [ 34 , 36 , 37 , 39 ], osteocalcin (OCN) [ 30 , 31 , 32 , 34 , 36 , 37 ], osteopontin (OPN) [ 30 , 31 ], osteonectin (ON) [ 29 , 31 ], Runx-2 [ 30 , 34 , 37 ], platelet endothelial cell adhesion molecule (PECAM-1) [ 31 ], mineralization [ 30 , 31 , 34 , 35 , 36 , 37 , 39 ] and viability [ 29 ...…”

“…The mentioned studies examined different parameters of human cells, for instance expression levels of ALP-conversion rates and dentin matrix acidic phosphoprotein 1 (DMP-1) [ 29 , 30 , 31 , 35 , 36 ], dentin sialophosphoprotein (DSPP) [ 29 , 32 , 34 , 35 , 36 , 37 , 39 ], bone morphogenic protein 2 (BMP-2) [ 34 , 36 , 37 , 39 ], osteocalcin (OCN) [ 30 , 31 , 32 , 34 , 36 , 37 ], osteopontin (OPN) [ 30 , 31 ], osteonectin (ON) [ 29 , 31 ], Runx-2 [ 30 , 34 , 37 ], platelet endothelial cell adhesion molecule (PECAM-1) [ 31 ], mineralization [ 30 , 31 , 34 , 35 , 36 , 37 , 39 ] and viability [ 29 , 33 , 34 , 35 , 36 , 37 ]. For these investigations, especially dental pulp cells [ 29 , 31 , 33 , 35 , 36 , 37 , 39 ], dental pulp stem cel...…”

“…Therefore, 24 cultures per group with 3 replicates and 6 replicates per culture were established. The number of investigated primary cultures of dental cells in previous studies ranges from one culture [ 35 ], 4 cultures [ 33 , 39 ], 5 cultures [ 32 ] to about 90 individual carious primary teeth as part of an in vivo study [ 38 ]. In about 50% of the studies the quantity of cultures was not mentioned [ 29 , 31 , 34 , 36 , 37 ].…”

Inflammation and dysfunction in human aortic endothelial cells associated with poly‐l‐lactic acid degradation in vitro are alleviated by curcumin

“…As a classic marker, NF‐κb plays a key role in the inflammatory response (Sethi et al, ). Expression of NF‐κb associated with PLLA was found to be a component of drug delivery system and causes no inflammation (Soares et al, ). However, in our precious study, NF‐κb expression associated with PLLA degradation extract was observed with dose‐dependency (Chen et al, ), which was confirmed by Western bolt in the present study.…”

Evaluation of human dental stem cell growth characteristics and cellular morphological changes in response to extracellular matrix nanotopography

“…PLLA nanofiber architecture structurally simulates collagen fibers and directly modifies cell behaviours, including adhesion, proliferation, and differentiation. The regenerative potential of dental pulp cells/NF-PLLA constructs has been investigated in various studies 21. Thus, PLLA nanofibers were used as the in vitro structural biomimetic of the native nanotopography found in the ECM/stem cell niche in vivo.…”