Review

Authors: Monal Patel, Alaa Guni, Luigi Nibali...

OBJECTIVES

To assess treatment options for the reconstruction of the lost interdental papilla and to evaluate evidence for their efficacy.

METHODS

An electronic search (Medline, Embase and the Cochrane Library Database and OpenGray) and a hand search were carried out to identify all types of studies investigating interdental papilla reconstruction (except for reviews) with a minimum of 3 months follow-up.

RESULTS

Forty-five studies were included in the study including 7 RCTs, 2 cohort studies, 19 case series and 17 case reports. Fifteen studies reported on the use of hyaluronic acid, 6 studies on platelet-rich fibrin, 16 studies on soft tissue grafting, 4 studies on orthodontics and 4 on additional modalities. The most common outcome measures were black triangle dimensions and papillary fill percentage. Meta-analysis was not possible due to the high heterogeneity of the studies.

CONCLUSION

There are various options for interdental papilla reconstruction of which hyaluronic acid injections, PRF, surgical grafting and orthodontics seem to improve outcomes at a minimum 3 months. The use of soft tissue grafting with sub-epithelial connective tissue graft seems to be associated with the most robust evidence for the longer-term reduction of 'black triangles'. There is insufficient evidence to make recommendations to clinicians. Further research is needed in the form of well conducted RCTs with longer follow ups and patient reported outcome measures.

CLINICAL RELEVANCE

Patients frequently complain about the appearance of black triangles and their management options seem unclear. This systematic review provides insight into the available reconstructive options.

Topics: Humans; Gingiva; Hyaluronic Acid; Dental Care; Electronics

PubMed: 38231354
DOI: 10.1007/s00784-023-05409-0

Meta-Analysis

Authors: Goran I Benic, Javier Mir-Mari, Christoph H F Hämmerle...

PURPOSE

To test whether or not immediate loading of single-implant crowns renders different results from early and conventional loading with respect to implant survival, marginal bone loss, stability of peri-implant soft tissue, esthetics, and patient satisfaction.

MATERIALS AND METHODS

An electronic search of Medline and Embase databases including studies published prior to August 1, 2012, was performed and complemented by a manual search. Randomized controlled trials (RCTs) comparing different loading protocols of single-implant crowns with a follow-up after restoration of at least 1 year were included. A meta-analysis yielded odds ratios (OR) and standardized mean differences (SMD) together with the corresponding 95% confidence intervals (95% CI).

RESULTS

The search provided 10 RCTs comparing immediate and conventional loading and 1 RCT comparing immediate and early loading. When assessing the implant survival at 1 year of loading, the meta-analysis of 10 studies found no significant differences between immediate and conventional loading (OR = 0.75; 95% CI: 0.32 to 1.76). The total difference of marginal bone loss during the first year of function between immediate and conventional loading protocols in 7 RCTs did not reach statistical significance (SMD = -0.05 mm; 95% CI: -0.41 to 0.31 mm). There were no significant differences between immediate and conventional loading regarding implant survival and marginal bone loss at 2, 3, and 5 years of loading. Three RCTs comparing the change of papilla level between immediate and conventional loading identified no significant differences. One study investigated the recession of the buccal mucosa after implant placement and found significantly inferior soft tissue loss for immediate loading as compared to conventional loading. Two RCTs investigated the recession of the buccal mucosa after insertion of the definitive crown and found no differences between immediate and conventional loading. The esthetics and the patient satisfaction were assessed in one and two RCTs, respectively. There were no significant differences between immediate and conventional loading.

CONCLUSIONS

Immediately and conventionally loaded single-implant crowns are equally successful regarding implant survival and marginal bone loss. This conclusion is primarily derived from studies evaluating implants inserted with a torque ≥ 20 to 45 Ncm or an implant stability quotient (ISQ) ≥ 60 to 65 and with no need for simultaneous bone augmentation. Immediately and conventionally loaded implants do not appear to differently affect the papilla height during the first year of loading. Due to the heterogeneity of the time point of baseline measurements and contradictory findings in the studies, it is difficult to draw clear conclusions regarding the recession of the buccal mucosa. With respect to the assessment of esthetic outcomes and patient satisfaction, the data available remain inconclusive.

Topics: Female; Humans; Middle Aged; Alveolar Bone Loss; Bone Density; Crowns; Dental Implantation, Endosseous; Dental Implants, Single-Tooth; Dental Restoration Failure; Gingival Recession; Immediate Dental Implant Loading; Mandible; Maxilla; Patient Satisfaction; Randomized Controlled Trials as Topic; Time Factors; Torque

PubMed: 24660200
DOI: 10.11607/jomi.2014suppl.g4.1

Authors: Hong Hu, Yufeng Duan, Kun Wang...

Mammalian teeth develop from the inductive epithelial-mesenchymal interaction, an important mechanism shared by many organs. The cellular basis for such interaction remains elusive. Here, we generate a dual-fluorescence model to track and analyze dental cells from embryonic to postnatal stages, in which Pitx2 epithelium and Msx1 mesenchyme are sufficient for tooth reconstitution. Single-cell RNA sequencing and spatial mapping further revealed critical cellular dynamics during molar development, where tooth germs are organized by Msx1Sdc1 dental papilla and surrounding dental niche. Surprisingly, niche cells are more efficient in tooth reconstitution and can directly regenerate papilla cells through interaction with dental epithelium. Finally, from the dental niche, we identify a group of previously unappreciated migratory Msx1 Sox9 cells as the potential cell origin for dental papilla. Our results indicate that the dental niche cells directly contribute to tooth organogenesis and provide critical insights into the essential cell composition for tooth engineering.

Topics: Tooth

PubMed: 36476878
DOI: 10.1016/j.celrep.2022.111737

Comparative Study Review

Authors: G T-J Huang, S Gronthos, S Shi...

To date, 5 different human dental stem/progenitor cells have been isolated and characterized: dental pulp stem cells (DPSCs), stem cells from exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSCs), stem cells from apical papilla (SCAP), and dental follicle progenitor cells (DFPCs). These postnatal populations have mesenchymal-stem-cell-like (MSC) qualities, including the capacity for self-renewal and multilineage differentiation potential. MSCs derived from bone marrow (BMMSCs) are capable of giving rise to various lineages of cells, such as osteogenic, chondrogenic, adipogenic, myogenic, and neurogenic cells. The dental-tissue-derived stem cells are isolated from specialized tissue with potent capacities to differentiate into odontogenic cells. However, they also have the ability to give rise to other cell lineages similar to, but different in potency from, that of BMMSCs. This article will review the isolation and characterization of the properties of different dental MSC-like populations in comparison with those of other MSCs, such as BMMSCs. Important issues in stem cell biology, such as stem cell niche, homing, and immunoregulation, will also be discussed.

Topics: Bone Marrow Cells; Cell Differentiation; Cell Lineage; Dental Papilla; Dental Pulp; Dental Sac; Humans; Mesenchymal Stem Cells; Periodontal Ligament; Regeneration; Tissue Engineering; Tooth; Tooth, Deciduous

PubMed: 19767575
DOI: 10.1177/0022034509340867

Authors: Martyna Smeda, Kerstin M Galler, Melanie Woelflick...

Both the dental pulp and the apical papilla represent a promising source of mesenchymal stem cells for regenerative endodontic protocols. The aim of this study was to outline molecular biological conformities and differences between dental pulp stem cells (DPSC) and stem cells from the apical papilla (SCAP). Thus, cells were isolated from the pulp and the apical papilla of an extracted molar and analyzed for mesenchymal stem cell markers as well as multi-lineage differentiation. During induced osteogenic differentiation, viability, proliferation, and wound healing assays were performed, and secreted signaling molecules were quantified by enzyme-linked immunosorbent assays (ELISA). Transcriptome-wide gene expression was profiled by microarrays and validated by quantitative reverse transcription PCR (qRT-PCR). Gene regulation was evaluated in the context of culture parameters and functionality. Both cell types expressed mesenchymal stem cell markers and were able to enter various lineages. DPSC and SCAP showed no significant differences in cell viability, proliferation, or migration; however, variations were observed in the profile of secreted molecules. Transcriptome analysis revealed the most significant gene regulation during the differentiation period, and 13 biomarkers were identified whose regulation was essential for both cell types. DPSC and SCAP share many features and their differentiation follows similar patterns. From a molecular biological perspective, both seem to be equally suitable for dental pulp tissue engineering.

Topics: Cell Differentiation; Cell Proliferation; Cells, Cultured; Dental Papilla; Dental Pulp; Mesenchymal Stem Cells; Osteogenesis; Stem Cells

PubMed: 35269758
DOI: 10.3390/ijms23052615

Review

Authors: Shizrah Jamal, Meisha Gul, Farhan Raza Khan...

BACKGROUND

Access to apical root canal system is gained after flap elevation using various incision techniques. Soft-tissue healing after periradicular surgery may include gingival recession, papilla recession, changes in probing depth, and clinical attachment loss.

OBJECTIVE

The objective of this study was to compare the effect of full sulcular flap design versus papilla-sparing flap design on the periodontal parameters in periradicular surgeries.

MATERIALS AND METHODS

It was a systematic review and meta-analysis. Electronic and manual searches were conducted in multiple databases including PubMed, Dental and Oral Sciences, Cochrane, and CINAHL Plus until May 2019. Initial search yielded 2575 studies with 5 articles meeting the inclusion criteria. The primary outcomes assessed were gingival recession and change in the papilla height. The secondary outcomes evaluated were probing depth, clinical attachment loss, postoperative pain, bleeding, and discomfort. Random-effects model was employed for computation of effect size, and forest plots were made.

RESULTS

Out of the five articles that satisfied the inclusion criteria, three were randomized control trials and two were nonrandom trials. No significant differences were found in the gingival recession ( = 0.79), papilla height ( = 0.55), gingival bleeding, and plaque indices. Statistically significant differences in probing depth ( = 0.006) and clinical attachment loss ( = 0.0004) were observed for the two flap designs in probing depth ( = 0.006) and clinical attachment loss ( = 0.0004).

CONCLUSIONS

The present systematic review and meta-analysis showed that probing depth and attachment loss are affected by the choice of flap design. On the other hand, gingival recession and papilla height are not influenced by the type of incision. However, finding of the present review may change if more studies on this topic will be included in the future. Therefore, more clinical trials with long-term follow-ups are needed.

PubMed: 34158683
DOI: 10.4103/jisp.jisp_290_20

Review

Authors: Mizuki Nagata, Noriaki Ono, Wanida Ono...

The dental pulp, a non-mineralized connective tissue uniquely encased within the cavity of the tooth, provides a niche for diverse arrays of dental mesenchymal stem cells. Stem cells in the dental pulp, including dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHEDs) and stem cells from apical papilla (SCAPs), have been isolated from human tissues with an emphasis on their potential application to regenerative therapies. Recent studies utilizing mouse genetic models shed light on the identities of these mesenchymal progenitor cells derived from neural crest cells (NCCs) in their native conditions, particularly regarding how they contribute to homeostasis and repair of the dental tissue. The current concept is that at least two distinct niches for stem cells exist in the dental pulp, e.g., the perivascular niche and the perineural niche. The precise identities of these stem cells and their niches are now beginning to be unraveled thanks to sophisticated mouse genetic models, which lead to better understanding of the fundamental properties of stem cells in the dental pulp and the apical papilla in humans. The new knowledge will be highly instrumental for developing more effective stem cell-based regenerative therapies to repair teeth in the future.

Topics: Animals; Biomarkers; Dental Papilla; Dental Pulp; Mice; Models, Genetic; Stem Cell Niche; Stem Cells

PubMed: 32803323
DOI: 10.1007/s00441-020-03271-0

Review

Authors: Li Zeng, Hong He, Mingjie Sun...

Dental follicles are necessary for tooth eruption, surround the enamel organ and dental papilla, and regulate both the formation and resorption of alveolar bone. Dental follicle progenitor cells (DFPCs), which are stem cells found in dental follicles, differentiate into different kinds of cells that are necessary for tooth formation and eruption. Runt-related transcription factor 2 (Runx2) is a transcription factor that is essential for osteoblasts and osteoclasts differentiation, as well as bone remodeling. Mutation of Runx2 causing cleidocranial dysplasia negatively affects osteogenesis and the osteoclastic ability of dental follicles, resulting in tooth eruption difficulties. Among a variety of cells and molecules, Nel-like molecule type 1 (Nell-1) plays an important role in neural crest-derived tissues and is strongly expressed in dental follicles. Nell-1 was originally identified in pathologically fused and fusing sutures of patients with unilateral coronal synostosis, and it plays indispensable roles in bone remodeling, including roles in osteoblast differentiation, bone formation and regeneration, craniofacial skeleton development, and the differentiation of many kinds of stem cells. Runx2 was proven to directly target the Nell-1 gene and regulate its expression. These studies suggested that Runx2/Nell-1 axis may play an important role in the process of tooth eruption by affecting DFPCs. Studies on short and long regulatory noncoding RNAs have revealed the complexity of RNA-mediated regulation of gene expression at the posttranscriptional level. This ceRNA network participates in the regulation of Runx2 and Nell-1 gene expression in a complex way. However, non-study indicated the potential connection between Runx2 and Nell-1, and further researches are still needed.

Topics: Bone Remodeling; Calcium-Binding Proteins; Cell Differentiation; Core Binding Factor Alpha 1 Subunit; Dental Sac; Humans; Osteogenesis; RNA; Stem Cells; Tooth Eruption; Transcription Factors

PubMed: 36175952
DOI: 10.1186/s13287-022-03140-3

Authors: Karla-Mayra Rezende, Marcelo Bönecker, Luciana Côrrea...

BACKGROUND

Dental Mesenchymal stem cells has prompted great for cell-based therapeutics. But no one knows for sure what the true potential of these cells, since most of the studies were done in isolation, using as source, different donors or different cell processing conditions.

MATERIAL AND METHODS

An enriched population of cells positive for CD146, STRO-1, and CD90 was isolated of third molars teeth indicated for extraction of patient with of 16 years old. Analysis of cell kinetics, and subcellular tests were performed to assess the presence of minor and trace elements by using synchrotron radiation x-ray fluorescence microscopy.

RESULTS

In the cell kinetics assays, the enriched populations showed generally slower growth as compared to those that were non-enriched. In comparison between the pulp and papilla populations, the derived pulp grew more rapidly than that derived from the papilla. The CD90 + cells exhibited a smaller pulp area compared to other populations, but the papilla of these cells exhibited a larger area. The CD90 + cells exhibited higher amounts of P, S, Cl, K, and Ca, while the Cu and Zn exhibited more than CD146-. STRO1 - exhibited K and Cu. For both the pulp and the papilla, multipotent stem cells positive for all three markers were present.

CONCLUSIONS

Although they have been obtained from the same tooth and donor, as well as were grown, the populations derived from these two tissues have different growth morphology and kinetics. The biochemical differences show different metabolic patterns, reflecting in part the growth differences. Synchrotron radiation, dental stem cells, mesenchymal stem cells, chemical composition.

PubMed: 34987718
DOI: 10.4317/jced.58819

Exploring the role of DNMT1 in dental papilla cell fate specification during mouse tooth germ development through integrated single-cell transcriptomics and bulk RNA sequencing.

Authors: Dahlia Eldeeb, Hiroyuki Okada, Yutaka Suzuki...

OBJECTIVES

This study aimed to investigate the regulatory mechanisms governing dental mesenchymal cell commitment during tooth development, focusing on odontoblast differentiation and the role of epigenetic regulation in this process.

METHODS

We performed single-cell RNA sequencing (scRNA-seq) of dental cells from embryonic day 14.5 (E14.5) mice to understand the heterogeneity of developing tooth germ cells. Computational analyses including gene regulatory network (GRN) assessment were conducted. We validated our findings using immunohistochemistry (IHC) and in vitro loss-of-function analyses using the DNA methyltransferase 1 (DNMT1) inhibitor Gsk-3484862 in primary dental mesenchymal cells (DMCs) isolated from E14.5 mouse tooth germs. Bulk RNA-seq of Gsk-3484862-treated DMCs was performed to identify potential downstream targets of DNMT1.

RESULTS

scRNA-seq analysis revealed diverse cell populations within the tooth germs, including epithelial, mesenchymal, immune, and muscle cells. Using single-cell regulatory network inference and clustering (SCENIC), we identified Dnmt1 as a key regulator of early odontoblast development. IHC analysis showed the ubiquitous expression of DNMT1 in the dental papilla and epithelium. Bulk RNA-seq of cultured DMCs showed that Gsk-3484862 treatment upregulated odontoblast-related genes, whereas genes associated with cell division and the cell cycle were downregulated. Integrated analysis of bulk RNA-seq data with scRNA-seq SCENIC profiles was used to identify the potential Dnmt1 target genes.

CONCLUSIONS

Dnmt1 may negatively affect odontoblast commitment and differentiation during tooth development. These findings contribute to a better understanding of the molecular mechanisms underlying tooth development and future development of hard-tissue regenerative therapies.

Topics: Animals; Mice; DNA (Cytosine-5-)-Methyltransferase 1; Single-Cell Analysis; Tooth Germ; Dental Papilla; Cell Differentiation; Odontoblasts; Sequence Analysis, RNA; Odontogenesis; Transcriptome; Immunohistochemistry; Gene Regulatory Networks

PubMed: 38942194
DOI: 10.1016/j.job.2024.06.010