Table 2 An overview of these studies on cell-based tissue engineering

BMMSCs

Cell suspension

Minimal medium

Rat model of periodontitis

Comparing the BMMSCs injection group to the control groups, clinical examinations, X-rays, and histological analyses demonstrated considerable periodontal tissue regeneration. The inflammatory mediators interleukin 1β (IL-1β), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) were also blocked

[17]

hPDLSCs

Cell sheets

Temperature responsive dishes

CB-17/Icr-scid/scid mice

The hPDLSCs sheets exhibited no microbial contamination, strong periostin expression, and alkaline phosphatase activity. In vivo, it led immune-deficient rats to develop cementum and PDL-like tissue

[26]

Human DPSCs (hDPSCs)

Cell sheets and cell suspension

20.0 ug/ml Vc

Miniature pigs of the periodontitis

As compared to hDPSCs injection, hDPSCs sheets demonstrated a greater ability for bone repair

[20]

Rat PDL Cs and osteoblast like cells (MC3T3-E1cells)

Composite cell sheets

Temperature responsive dishes

Immunocompromised mice

In ectopic and orthotopic transplantation, a composite cell sheet containing 10 layers of cells regenerated functional PDL-like fibers and similar alveolar bone periodontal ligament structure

[28]

hPDLSCs and hJBMMSCs

Composite cell sheets

50 μg/ml L-ascorbic acid

Nude mice of ectopic transplantation

The composite cell sheets enhanced the expression of genes and proteins associated with bone and extracellular matrix

[29]

Human HUVECs and PDLCs

Composite cell sheets

Temperature-responsive culture dishes

Transplanted subcutaneously into immunodeficient mice

The cell sheets resulted in the creation of PDL-like tissues in vivo and increased numbers of blood vessel lumens while reducing necrosis and inflammation of the transplanted tissue

[30]

hPDLSCs, human alveolar bone stem cells (hABSCs) and human gingival margin-derived cells

A calcium phosphate-coated melt electrospinning polycaprolactone (CaP-PCL) scaffold that supports cell sheets

Temperature-responsive culture dishes and 50 μg/mlVc

Periodontal defect model in the athymic rat

Significant periodontal attachment formation was observed with the addition of hABSCs and sheets of hPDLCs. Human gingival margin-derived cell sheets failed to induce periodontal regeneration on the root surface as well as suppressed bone formation within the CaP-PCL scaffold

The scaffold optimized the regenerative effect of tooth-derived stem cells on cementum, PDL and alveolar bone. A well aligned PDL-like collagen fibers are generated which are inserted into the cementum and alveolar bone in mice

[34]

DPSCs, PDLSCs and ABSCs

3D printing

PCL/HA scaffold

Human amelogenin, and bone morphogenetic factor(BMP)-2

Transplanted subcutaneously into immunodeficient mice (Harlan)

The scaffolds optimized the regenerative effect of dental stem cells on cementum, PDL and alveolar bone. A well-aligned PDL-like collagen fibers are generated which are inserted into the cementum and alveolar bone in immunodeficient mice

[36]

Merino sheep PDLSCs and osteoblast

A biphasic scaffold based on the electrospun loaded cell sheets

Osteogenic media

The immunodeficient subcutaneous model

Higher mineralization density and improved adherence to the dentin surface could be seen in biphasic scaffolds

[37]

hPDLSCs human GMSCs human osteoblast

A trilayer porous scaffold based on chitosan—human compartments

-

Ectopic model in nude mice

Scaffolds exhibit high biocompatibility with tissue growth and vascularization in the wild-type mice and identified in nude mice a rich mineralized matrix inside the medium molecular weight-chitosan area, with weakly mineralized deposits at the dentin contact

[38]

-

A porous tri-layered scaffold

Cementum protein 1, fibroblast growth factor 2(FGF2), and platelet-rich plasma derived growth factors

Maxillary periodontal defects in rabbits

On examination of the microcomputed tomography, porous trilayer structure had fully repaired the defect and closed the wound. In contrast to the other three groups, the newly produced cementum, fibrous PDL, and alveolar bone with distinct bony trabeculae were mostly formed

[39]

rBMSCs

Porous chitosan was created using PCE copolymer electrospun nanofibrous mats

–

Sprague–Dawley rats periodontal defects

The electrospinning scaffold stimulates in vitro directed organization and ligament generation of rBMSCs. In comparison with the other two groups, it demonstrated in vivo a more regular organization of regenerated PDL, a wider development of mature collagen fibers, and an increase in periostin expression

[42]

Ovine osteoblasts

A biphasic scaffold polycaprolactone melt electrospun scaffold

–

Ectopic model in athymic nude rats

Alkaline phosphatase activity and mineralization significantly increased in the CaP-coated group, while in vivo, there was more bone formation, more pronounced vascularization, and greater periodontal attachment on the dentin surface

[43]

–

3D-printed PCL scaffolds

rhPDGF-BB

Human clinical trials

The scaffold was uncovered at 13 months; however, at 14 months, they found a 3-mm increase in adhesion and 75.9% stent retention, with primarily connective tissue healing and no bone repair evidence

[49]

hPDLSCs

Bioscaffolds made by extrusion 3D bioprinting technology

–

–

A composite of SA/Gel/n-HA hydrogels exhibited well rheological properties and a high swelling rate suitable for the printed scaffolds, which indicated that they had sufficient porosity

[51]

hPDLSCs

3D cell-printing

–

Calvarial defect model in athymic rats

As compared to the cell seeding group, the printed group showed orderly connective tissue between the scaffold and the athymic rat cranial bone

[54]