Table 3 Various strategies for endogenous regeneration in periodontal regeneration

Stromal cell derived factor-1 (SDF-1) and BMP-2

Supramolecular

Rats with a maxillary periodontal bone deficiency

The release of these two bioactive substances from the hydrogel was precise, synchronized, and continuous, according to in vitro and in vivo data. And a better bone regeneration rate of 56.7% bone volume fraction was attained

[68]

CEMP1, FGF 2, platelet-rich plasma-derived growth factors

A scaffold made of trilayered nanocomposite hydrogel

Maxillary periodontal defects in the rabbits

Further evidence of the formation of new cementum, fibrous PDL, and alveolar bone with distinct bony trabeculae in contrast to those of the other three groups obtained from histological and immunohistochemical analyses

[39]

Vascular endothelial growth factor (VEGF) and BMP-2

Gelatin microparticles incorporated within the scaffold pores

Rat cranial critical size

Large quantities of bone growth were seen in the scaffold pores and along its outer surfaces in the dual release and BMP-2 groups. Osteoid secretion and mineralization were also noticeable, and new bone was frequently in close or direct contact with the scaffold interface. At 4 weeks, there was no discernible difference in blood vessel creation across the groups

[70]

VEGF,FGF2 and BMP-2

A biomimetic electrospun nanocomposite fibrous scaffold

Wistar rats

Although FGF2 and VEGF loaded scaffolds had a varied release pattern, both of the dual growth factor loaded scaffolds (VEGF + BMP-2/FGF2 + BMP-2) improved vascularization and new bone production

[71]

CM obtained from cultured PDLSCs

–

A rat periodontal defect model

TNF-mRNA levels in healing periodontal tissues were reduced as a consequence, while those in the IFN-stimulated monocyte/macrophage cell line RAW were inhibited

[77]

CM from GMSCs and PDLSCs

Collagen membranes loaded with concentrated CM

A rat periodontal defect model

They both enhanced periodontal regeneration Immunostaining results showed that TNF-α and IL-1 expression levels were reduced by the CM transplantation whereas IL-10 expression levels were elevated

[78]

Human GMSCs-derived exosomes

Local injection

Ligature-induced periodontitis model in mice

Exosomal miR-1260b was reported to target the Wnt5a-mediated RANKL pathway and limit its osteoclastogenic activity in GMSCs-derived exosomes, which showed anti-osteoclastogenic acts

[79]

Human MSCs exosome

Collagen sponges

SD Rat periodontal defect model

It could promote migration and proliferation by activating prosurvival AKT and ERK signaling via CD73, which results in the regeneration of periodontium

[81]

SHED-derived exosome

–

In vitro

According to the results, Wnt3a and BMP-2 were carried by the conditioned SHED-Exo-increased PDLSCs, which led to their accelerated osteogenic differentiation

[82]

SHED-derived exosomes

β-TCP

Rat models of the periodontal defect

Through the modulation of angiogenesis and osteogenesis, the exosomes/β-TCP group aids in the healing of alveolar bone defects

[83]

Decellularized tooth bud-ECM structures

–

Extraction sockets of adult piglets

It was discovered that the complex structure regularly directed the creation of well-organized bioengineered teeth with dimensions similar to those of natural human teeth

[87]

Decellularized PDLSCs sheets

PCL

A rat periodontal defect model

Decellularized PDLSCs sheets could promote angiogenesis and increase periodontal attachment formation

[88]

Decellularized human PDLSCs sheets

PCL/gelatin nanofibers

A rat periodontal defect model

It leaded to bone, dental bone, and periodontal ligament formation after 4 weeks

[89]

Sclerostin-neutralizing monoclonal antibody (Scl-Ab)

Administered subcutaneously and locally

The experimental periodontitis rats model

In terms of linear alveolar bone loss, volumetric measures of bone support, such as bone volume fraction and tissue mineral density, as well as higher levels of the serum procollagen type I amino-terminal propeptide and bone-formation markers osteocalcin, maxillary bone healing was significantly improved after 6 weeks of Scl-Ab

[97]

Sclerostin antibody (SAB) alone and DKK1 antibody (DAB)

Systemic administration

A chronic rat maxillary molar extraction model

Additionally, because of hypo-occlusion and increased alveolar bone density, the opposing mandible experienced bone loss that SAB and SAB + DAB completely stopped

[98]

Complement, C3 inhibitor (CP40)

Locally administration

Nonhuman primates and C3-deficient or wild-type mice

When compared to a control therapy, local Cp40 administration prevented ligature-induced periodontitis and bone loss and lowered osteoclastogenesis in bone biopsy specimens in nonhuman primates

[101]