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Management of avulsed teeth after replantation often leads to an unfavorable outcome. Damage to the thin and vulnerable periodontal ligament is the key reason for failure. Cell- or stem cell-based regenerative medicine has emerged in the past two decades as a promising clinical treatment modality to improve treatment outcomes. This concept has also been tested for the management of avulsed teeth in animal models. This review focuses on the discussion of limitation of current management protocols for avulsed teeth, cell-based therapy for periodontal ligament (PDL) regeneration in small and large animals, the challenges of de novo regeneration of PDL on denuded root in the edentulous region using a mini-swine model, and establishing a prospective new clinical protocol to manage avulsed teeth based on the current progress of cell-based PDL regeneration studies. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-022-02700-x.

2-Aminoethyl methacrylate (AEMA)–modified hyaluronic acid (HA) hydrogels with tunable swelling, degradation, and rheological properties were developed to maintain the native spherical and stemness of human dental pulp stem cells (DPSCs). Two molecular weights (MW) of HA, 18 and 270 kDa, and 25% degree of AEMA substitution were used to synthesize the HA macromers and hydrogels. The HA macromers were characterized by 1H NMR, and the AEMA-HA hydrogels were synthesized by UV polymerization. The swelling, hydrolytic degradation, and rheological properties of the hydrogels strongly depended on the MW of HA. The degradation rate decreased and the storage modulus increased with the increase in the MW of HA. The storage modulus of the hydrogels decreased with degradation of the hydrogels. The hydrogels were not cytotoxic to DPSCs evidenced by MTT assay, Hoechst 33342 live cell staining, and propidium iodide dead cell staining. The hydrogels maintained the native spherical morphology and stemness of DPSCs when the hydrogels’ storage moduli were in the ranges of 486–681 Pa. In contrast, DPSCs grown on 2D cell culture substrates showed a flat and elongated shape and could not maintain their native spherical shape. The hydrogels increased the expression of the stemness including NANOG and SOX2 of DPSCs (3 and 24 folds, respectively) when their storage modulus was 681.41 ± 92.81 Pa in comparison with DPSCs grown on 2D cell culture plates. The designed AEMA-HA hydrogels mimic the in vivo 3D environment to grow DPSCs. Thus, they appear to have great potential for clinical applications in regenerative medicine and other therapeutic remedies after further optimization in the future. Regenerative medicine is a translational approach that offers the possibility to replace or heal the diseased or damaged tissues caused by trauma, age, infection, cancer, or inherited defects. Such reinstatement of the functionality or healing of the damaged cells or tissues often includes the combination of numerous strategies including the use of biomaterials/scaffolds, stem cells, growth factors, and small molecules. In this study, we used hyaluronic acid (HA), a naturally occurring polysaccharide biopolymer commonly found in the extracellular matrix of connective tissues, to synthesize 3D hydrogel scaffolds for growing human dental pulp stem cells (DPSCs). We evaluated the effects of the molecular weight of HA, and the swelling, degradation, and rheological properties of the hydrogels on maintaining the native spherical and stemness of DPSCs for future therapeutic applications including regenerative medicine.

The potential of human mesenchymal stromal/stem cells (MSCs) including oral stem cells (OSCs) as a cell source to derive functional neurons has been inconclusive. Here we tested a number of human OSCs for their neurogenic potential compared to non-OSCs and employed various neurogenic induction methods. OSCs including dental pulp stem cells (DPSCs), gingiva-derived mesenchymal stem cells (GMSCs), stem cells from apical papilla and non-OSCs including bone marrow MSCs (BMMSCs), foreskin fibroblasts and dermal fibroblasts using non-neurosphere-mediated or neurosphere-mediated methods to guide them toward neuronal lineages. Cells were subjected to RT-qPCR, immunocytofluorescence to detect the expression of neurogenic genes or electrophysiological analysis at final stage of maturation. We found that induced DPSCs and GMSCs overall appeared to be more neurogenic compared to other cells either morphologically or levels of neurogenic gene expression. Nonetheless, of all the neural induction methods employed, only one neurosphere-mediated method yielded electrophysiological properties of functional neurons. Under this method, cells expressed increased neural stem cell markers, nestin and SOX1, in the first phase of differentiation. Neuronal-like cells expressed βIII-tubulin, CNPase, GFAP, MAP-2, NFM, pan-Nav, GAD67, Nav1.6, NF1, NSE, PSD95, and synapsin after the second phase of differentiation to maturity. Electrophysiological experiments revealed that 8.3% of DPSC-derived neuronal cells and 21.2% of GMSC-derived neuronal cells displayed action potential, although no spontaneous excitatory/inhibitory postsynaptic action potential was observed. We conclude that DPSCs and GMSCs have the potential to become neuronal cells in vitro, therefore, these cells may be used as a source for neural regeneration.

This is to compare the volumes of irrigant apically extruded by five irrigation systems in an artificial socket model simulating clinical conditions. Twenty extracted human single-rooted teeth were enlarged to size 40/04 and then embedded in silicone impression material. The root canal space was irrigated with nominal 3% sodium hypochlorite (NaOCl) using standard needle irrigation (SNI) with a 30-gauge notched needle, EndoActivator (EA), XP Endo Finisher (XP Endo), EndoVac (EV), and photon-induced photoacoustic streaming (PIPS). Extruded NaOCl was collected, reacted with taurine to form taurine-monochloramine, and absorbance of taurine-monochloramine was measured at 252 nm using a spectrophotometer. The five irrigation systems were compared with repeated measures ANOVA and pairwise comparisons. The EV group had very low extrusion (mean ± SD = 0.12 ± 0.2 μL) and differed significantly from the other four groups (P ≤ 0.001). Larger volumes of irrigant were extruded in the other irrigation groups. There were no significant differences in the extruded volumes among the SNI (7.4 ± 3.4 μL), EA (7.0 ± 6.1 μL), and XP Endo (7.8 ± 4.1 μL) groups (P = 1). The PIPS group had the highest mean extruded volume (12.9 ± 6.8 μL) and differed significantly from SNI (P = 0.030), EV (P

The evolutionarily conserved dolichol-P-dependent N-acetylglucosamine-1-P transferase gene, ALG7, functions by initiating the dolichol pathway of protein N-glycosylation. In yeast, ALG7 has a complex expression pattern and plays a critical role in diverse cellular functions, including proliferation and morphological response. In Chinese hamster ovary cells (CHO), ALG7 gives rise to three mRNAs of 1.5, 1.9 and 2.2 kb. We report results of RNA blotting assays, ribonuclease protection, PCR-amplification and sequencing of the CHO ALG7 transcripts 5' and 3' ends which suggest that the 1.5 and 1.9 kb transcripts are produced as a consequence of initiation at 2 distinct start sites, 350-379 bp apart. The transcriptional start site for the 1.5 kb mRNA is positioned between the first two in frame ATGs, while that of the 1.9 kb species is located upstream of these two in-frame ATGs. In order to test the translational competence of the 1.5 and 1.9 kb mRNAs, we constructed DNA templates specifying these transcripts and used them for in vitro transcription/translation. Our data show that the 1.9 kb mRNA served in the synthesis of 36 and 24 kDa species, as well as a low-abundance 32 kDa protein. The 1.5 kb transcript gave rise to a translation product of 32 kDa. The latter is synthesized in CHO cells and hamster submandibular glands. These results suggest the possibility that the 1.5 and 1.9 kb transcripts give rise to related protein isoforms with different lengths of their NH2-terminal regions.