Alveolar ridge dimensional changes following ridge preservation procedure with novel devices: part 3 - histological analysis in non-human primate model.

OBJECTIVES: This study sought to investigate the histological changes following tooth extraction, ridge preservation and augmentation, using novel devices designed to obturate the oral orifice of extraction sockets (SocketKAP™) and provide structural support for sockets with defective bony walls (SocketKAGE™) in a non-human primate model. MATERIAL AND METHODS: Six Macaca fascicularis were imaged by cone beam computed tomography to register their preoperative alveolar bone. Three teeth were extracted in each animal, yielding intact socket walls and were divided into three intervention groups: unassisted healing negative control (Group A); SocketKAP™ (Group B); filled with anorganic bovine bone mineral (ABBM) + SocketKAP™ (Group C). Three additional teeth were extracted in each animal, followed by surgical resection of the entire buccal alveolar bone and divided into three groups: negative control (Group D); SocketKAP™ + SocketKAGE™ (Group E); ABBM + SocketKAP™ + SocketKAGE™ (Group F). Animals were euthanized after 12 weeks, and treatment sites were examined by histology and histomorphometric analysis. RESULTS: Control sockets with unassisted healing (Groups A and D) underwent severe loss of bone width, height and total area (approximately 40-60% loss). Application of SocketKAP™ in sites with intact walls, as well as SocketKAP™ plus SocketKAGE™ in sites with defective buccal walls lead to higher preservation of alveolar bone height after 12 weeks post-intervention. Addition of ABBM leads to the highest degree of alveolar bone dimensional preservation. Control sites with unassisted healing (Groups A and D), as well as sites treated with extraction socket devices (Groups B and E) without ABBM yielded higher percentage of vital bone, compared with sites filled with ABBM (Groups C and F). No adverse histological responses were noted to SocketKAP™ or SocketKAGE™ devices. CONCLUSIONS: SocketKAP™ + SocketKAGE™ devices proved effective in reducing post-extraction alveolar bone resorption mediating favorable wound healing within sockets. Addition of ABBM was associated with reduced volumetric loss, although the bone fill was characterized by less mature as well as more woven bone.

Alveolar ridge dimensional changes following ridge preservation procedure with novel devices: Part 1--CBCT linear analysis in non-human primate model.

AIM: This study sought to investigate dimensional changes to the alveolar bone following extraction and application of novel devices used for obturation of socket orifice (socket cap) and space maintenance in sockets with facial dehiscence (socket cage). MATERIAL AND METHODS: Six Macaca fascicularis had six teeth each removed according to the following intervention groups (groups A-C intact alveolar bone; D-E facial dehiscence): negative control (A); socket obturated with cap (B); filled with anorganic bovine bone mineral (ABBM) + socket cap (C); dehiscence negative control (D); socket cap + socket cage (E); ABBM + socket cap + socket cage (F). Serial CBCT scans at preoperatively, 6 and 12 weeks following intervention were compared to quantify linear alveolar bone alterations. RESULTS: Without therapeutic intervention, intact sockets exhibited significant reduction in width at the crestal 2 mm of the ridge crest within 6 weeks. Compared with the negative control sites which lost up to 52% of crestal bone width, sites treated with socket cap + ABBM lost at most 4% of bone width at the crestal 2 mm. Similar results were seen in the dehiscence groups, with the combination of socket cap + socket cage + ABBM maintaining the greatest socket width and height dimensions. CONCLUSIONS: Results from the current non-human primate study suggest that the socket cap and socket cage devices, when used in conjunction with xenograft proved effective in minimizing post-extraction socket width loss and height seen in both intact sockets and sockets with facial dehiscence defects.

Distal-less homeobox 2 promotes the osteogenic differentiation potential of stem cells from apical papilla.

Dental tissue-derived mesenchymal stem cells (MSCs) are a reliable cell source for dental tissue regeneration. However, the molecular mechanisms underlying the directed differentiation of MSCs remain unclear; thus, their use is limited. The histone demethylase, lysine (K)-specific demethylase 4B (KDM4B), plays critical roles in the osteogenic commitment of MSCs by up-regulating distal-less homeobox 2 (DLX2) expression. The DLX2 gene is highly expressed in dental tissue-derived MSCs but the roles of DLX2 in osteogenesis are unclear. Here, we investigate DLX2 function in stem cells from apical papilla (SCAPs). We found that, in vitro, DLX2 expression was up-regulated in SCAPs by adding BMP4 and by inducing osteogenesis. The knock-down of DLX2 in SCAPs decreased alkaline phosphatase (ALP) activity and mineralization. DLX2 depletion affected the mRNA expression of ALP, bone sialoprotein (BSP) and osteocalcin (OCN) and inhibited SCAP osteogenic differentiation in vitro. Over-expression of DLX2 enhanced ALP activity, mineralization and the expression of ALP, BSP and OCN in vitro. In addition, transplant experiments in nude mice confirmed that SCAP osteogenesis was triggered when DLX2 was activated. Furthermore, DLX2 expression led to the expression of the key transcription factor, osterix (OSX) but not to the expression of runt-related transcription factor 2 (RUNX2). Taken together, these results indicate that DLX2 is stimulated by BMP signaling and enhances SCAP osteogenic differentiation by up-regulating OSX. Thus, the activation of DLX2 signaling might improve tissue regeneration mediated by MSCs of dental origin. These results provide insight into the mechanism underlying the directed differentiation of MSCs of dental origin.

Periodontal ligament stem cells in the periodontitis niche: inseparable interactions and mechanisms.

Periodontitis is characterized by the periodontium's pathologic destruction due to the host's overwhelmed inflammation to the dental plaque. The bacterial infections and subsequent host immune responses have shaped a distinct microenvironment, which generally affects resident periodontal ligament stem cells (PDLSCs). Interestingly, recent studies have revealed that impaired PDLSCs may also contribute to the disturbance of periodontal homeostasis. The putative vicious circle underlying the interesting "positive feedback" of PDLSCs in the periodontitis niche remains a hot research topic, whereas the inseparable interactions between resident PDLSCs and the periodontitis niche are still not fully understood. This review provides a microscopic view on the periodontitis progression, especially the quick but delicate immune responses to oral dysbacterial infections. We also summarize the interesting crosstalk of the resident PDLSCs with their surrounding periodontitis niche and potential mechanisms. Particularly, the microenvironment reduces the osteogenic properties of resident PDLSCs, which are closely related to their reparative activity. Reciprocally, these impaired PDLSCs may disrupt the microenvironment by aggravating the host immune responses, promoting aberrant angiogenesis, and facilitating the osteoclastic activity. We further recommend that more in-depth studies are required to elucidate the interactions of PDLSCs with the periodontal microenvironment and provide novel interventions for periodontitis.

Erratum to "Collagen Sponge Functionalized with Chimeric Anti-BMP-2 Monoclonal Antibody Mediates Repair of Critical-Size Mandibular Continuity Defects in a Nonhuman Primate Model".

[This corrects the article DOI: 10.1155/2017/8094152.].

Collagen Sponge Functionalized with Chimeric Anti-BMP-2 Monoclonal Antibody Mediates Repair of Critical-Size Mandibular Continuity Defects in a Nonhuman Primate Model.

Antibody-mediated osseous regeneration (AMOR) has been introduced by our research group as a tissue engineering approach to capture of endogenous growth factors through the application of specific monoclonal antibodies (mAbs) immobilized on a scaffold. Specifically, anti-Bone Morphogenetic Protein- (BMP-) 2 mAbs have been demonstrated to be efficacious in mediating bone repair in a number of bone defects. The present study sought to investigate the application of AMOR for repair of mandibular continuity defect in nonhuman primates. Critical-sized mandibular continuity defects were created in Macaca fascicularis locally implanted with absorbable collagen sponges (ACS) functionalized with chimeric anti-BMP-2 mAb or isotype control mAb. 2D and 3D analysis of cone beam computed tomography (CBCT) imaging demonstrated increased bone density and volume observed within mandibular continuity defects implanted with collagen scaffolds functionalized with anti-BMP-2 mAb, compared with isotype-matched control mAb. Both CBCT imaging and histologic examination demonstrated de novo bone formation that was in direct apposition to the margins of the resected bone. It is hypothesized that bone injury may be necessary for AMOR. This is evidenced by de novo bone formation adjacent to resected bone margins, which may be the source of endogenous BMPs captured by anti-BMP-2 mAb, in turn mediating bone repair.

[Effects of bleaching agents on the microleakage of class V cavities restored with glass-ionomer cements].

OBJECTIVE: To evaluate the effects of a bleaching gel and a whitening strip on the microleakage of three different glass-ionomer cements. METHODS: Forty-five freshly extracted human premolars were used and class V cavity was prepared on the buccal and lingual surfaces. The teeth were randomly assigned to A, B and C groups and restored as follows: Conventional strengthen glass-ionomer cement (Ketac Molar Easymix), compomer (F2000) and compomer (Dyract AP). Teeth were kept in distilled water at 37 degrees C for 7 days. Then the specimens were thermocycled for 500 times. Each group was randomly divided into 3 subgroups which were treated for 21 days with one of the following: Whitening strip (14% hydrogen peroxide), bleaching gel (10% carbamide peroxide), or distilled water (control). After bleaching, the teeth were placed in a solution of basic fuchsin dye for 24 hours, then the teeth were sectioned longitudinally to evaluate the dye penetration. The depth of staining along the tooth restoration interface was recorded with a stereomicroscope. RESULTS: There were no signicant differences between the two bleaching agents in microleakage of restorations (P>0.05). The two bleaching agents did not significantly affect the microleakage of compomer (P>0.05), whereas the microleakage of glass-ionomer cement in the experimental groups was higher than that in the control group (P<0.05). CONCLUSION: There are no significant differences in microleakage of restorations between bleaching gel (10% carbamide peroxide) and whitening strip (14% hydrogen peroxide). The two bleaching agents do not significantly affect the microleakage of compomer but adversely affect the microleakage of strengthen glass-ionomer cement.