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Citterio et al. Plast Aesthet Res 2020;7:41 I http://dx.doi.org/10.20517/2347-9264.2020.29 Page 11 of 20

stem cells [120,122] in intrabony defects. These RCTs differ in the type of stem cells selected (PDLSCs,
DPSCs, or UC-MSCs) and in their application for the regenerative procedure (chairside use or isolation,
differentiation, and cell culture in a laboratory). Shailini and coworkers [121] applied the concept of “stem cell
niche” to periodontal regeneration. In this prospective, randomized, single-blinded, controlled trial with
parallel design, 16 patients with one intrabony defect were treated. In the test group, PDLSCs collected
from an extracted tooth, together with the soft-tissue adherent to the extracted root surface and to the
alveolar socket (PDL tissue niche), were directly mixed to a gelatin sponge and implanted in the intrabony
defect. The control group was treated with an open flap debridement. The results after one year showed a
greater improvement in PD reduction, CAL gain, and radiographic defect resolution in the group treated
with PDLSCs; however, the differences were not statistically significant. No adverse effects were reported,
thus suggesting the safety of the procedure.

Similar to Shailini, Chen and coworkers [120] studied the efficacy of PDLSCs. PDLSCs harvested from an
extracted tooth were isolated, characterized, and grown into sheets in a laboratory. In this single-center
randomized trial, 41 intrabony defects were treated with either GTR and PDLSC sheets in combination
with demineralized bovine bone matrix or with GTR and demineralized bovine bone matrix alone.
The results after one year showed an increased alveolar bone height in both groups, without statistically
significant differences between groups. As for the clinical periodontal parameters, no statistically significant
differences were found for the increased CAL, PD, or GR between the cell and control groups. No adverse
effects in the use of PDL cells sheets were reported.

While Chen and Shailini evaluated the efficacy of PDLSCs, Ferrarotti and coworkers [122] evaluated the use
of micrografts containing DPSCs delivered into intrabony defects in a collagen scaffold. In this parallel,
double-blind, prospective randomized trial, 29 patients with an intrabony defect were treated with
either minimally invasive surgical technique (MIST) plus dental pulp micrografts in a collagen sponge
biocomplex (test) or MIST plus collagen sponge alone (control). The micrografts enriched in DPSCs
were obtained from the pulp chamber of an extracted tooth, dissociated by the use of a biological tissue
disaggregator (Rigenera Machine System, Rigenera; HBW, Turin, Italy), and then seeded on a collagen
sponge scaffold. After one year, the results showed a statistically significant greater PD reduction, CAL gain,
and radiographic bone defect fill in the group treated with DPSCs on a scaffold, compared to the scaffold
alone. No adverse effects were reported.

Instead of using dental stem cells, Dhote and coworkers [123] tested the efficacy of non-dental stem cells on
periodontal regeneration, focusing their attention on the umbilical cord MSCs (UC-MSCs). In this parallel
designed RCT, 24 periodontal intrabony defects in 14 patients were treated by either applying allogeneic
cord blood MSCs on a beta-tricalcium phosphate (beta-TCP) scaffold in combination with platelet-derived
growth factor-BB (rh-PDGF-BB) or by open flap debridement (OFD). The results after six months showed
significantly greater CAL gain, PPD reduction and radiographic defect fill in the group treated with a
combination of allogeneic UC-MSCs, rh-PDGF-BB, and beta-TCP scaffold compared to the OFD. No
adverse effects were reported demonstrating the safety of mesenchymal stem cells derived from umbilical
cord for dental tissue engineering.

An interesting field of application for stem cells is represented by defects that cannot be predictably treated
with the techniques available today, such as furcation defects or supracrestal regeneration. The application
of stem cells to enhance the regeneration of furcations was tested in an RCT by Akbay and coworkers [113] ,
which evaluated the periodontal regenerative potential of PL grafts in Grade II furcation defects. Ten
patients were treated in a split mouth design: on one side, a molar was treated with a coronally positioned
flap with autogenous PDLSCs grafts obtained from third molars, while, on the other side, with a coronally
positioned flap alone. PL remnants attached to cementum and cellular cementum were collected by