Biomedical Engineering Reference
In-Depth Information
cells markedly cause the contraction of collagen with a reduction down to ~30%, which
might affect pulp tissue regeneration (Huang et al., 2006).
Examples of synthetic polymers are polylactic acid (PLA), polyglycolic acid (PGA) or their
co-polymers, poly lactic-co-glycolic acid (PLGA). Recent experiments demonstrate that
DPSCs seeded onto PLGA scaffolds regenerate a pulp/dentin-like tissue (Huang, 2009).
Other artificial scaffolds are hydrogels, like polyethylene glycol (PEG)-based polymers, or
inorganic compounds such as hydroxyapatite (HA), tricalcium phosphate (TCP) and
calcium polyphosphate (CPP). These are used to enhance bone conductivity and have
proved to be very effective for tissue engineering of DPSCs (Wang et al., 2006).
Apart from DPSCs and an appropriate scaffold, dental pulp regeneration also requires the
use of growth factors and ECM molecules that induce specific differentiation pathways and
maintain the odontoblast phenotype. It is known that several factors, such as transforming
growth factor β (TGF), bone morphogenic proteins (BMPs), platelet-derived growth factor
(PDGF), fibroblast growth factor (FGF), and vascular endothelial growth factor (VEGF), are
secreted by odontoblasts and incorporated within the dentine matrix during dentinogenesis.
When these molecules are released from the dentin, they are bioactive and fully capable of
inducing cellular responses, as for example those that lead to the generation of reparative
dentin and to dental pulp repair (Casagrande et al., 2011).
Dental pulp tissue engineering is an emerging field that can potentially have a major impact
on oral health. However, the source of morphogens required for stem cell differentiation
into odontoblasts and the scaffold characteristics that are more conducive to odontoblastic
differentiation are still unclear. (Demarco 2010) investigated the effect of dentin and scaffold
porogen on the differentiation of human dental pulp stem cells (DPSCs) into
odontoblasts.Poly-L-lactic acid (PLLA) scaffolds were prepared in pulp chambers of
extracted human third molars using salt crystals or gelatin spheres as porogen. DPSCs
seeded in tooth slice/scaffolds or control scaffolds (without tooth slice) were either cultured
in vitro or implanted subcutaneously in immunodefficient mice.
DPSCs seeded in tooth slice/scaffolds but not in control scaffolds expressed putative
odontoblastic markers (DMP-1, DSPP, and MEPE) in vitro and in vivo. DPSCs seeded in
tooth/slice scaffolds presented lower proliferation rates than in control scaffolds between 7
and 21 days (p < 0.05). DPSCs seeded in tooth slice/scaffolds and transplanted into mice
generated a tissue with morphological characteristics similar to those of human dental
pulps. Scaffolds generated with gelatin or salt porogen resulted in similar DPSC
proliferation. The porogen type had a relatively modest impact on the expression of the
markers of odontoblastic differentiation. Collectively, this work shows that dentin-related
morphogens are important for the differentiation of DPSC into odontoblasts and for the
engineering of dental pulp-like tissues and suggest that environmental cues influence DPSC
behavior and differentiation potential.
Yang et al (Yang 2010) investigated, moreover the in vitro and in vivo behavior of dental
pulp stem cells (DPSCs) seeded on electrospun poly(epsilon-caprolactone) (PCL)/gelatin
scaffolds with or without the addition of nano-hydroxyapatite (nHA). For the in vitro
evaluation, DNA content, alkaline phosphatase (ALP) activity and osteocalcin (OC)
measurement showed that the scaffolds supported DPSC adhesion, proliferation, and
odontoblastic differentiation. Moreover, the presence of nHA upregulated ALP activity and
promoted OC expression. Real-time PCR data confirmed these results. SEM micrographs
qualitatively confirmed the proliferation and mineralization characteristics of DPSCs on
both scaffolds. Subsequently, both scaffolds seeded with DPSCs were subcutaneously
