Immediate implant placement vs. early implant treatment in the esthetic area. A 1-year randomized clinical trial.

OBJECTIVES: To assess the impact of implant placement and temporization timing on esthetic outcomes of single maxillary anterior implants with intact bone walls and interproximal bone. MATERIALS AND METHODS: Test group patients received an immediate implant with immediate provisional restoration and socket preservation, while patients in the control group received an early implant placement with guided bone regeneration and delayed loading. Patients were followed for 1 year after final prosthetic and pink esthetic score (PES), mid-buccal mucosal level (MBML), crestal bone changes (CBC), and peri-implant soft tissue parameters, and patient chair time was recorded. RESULTS: Fifty patients received the intended treatment (25 test and 25 control). No implants failed. PES after 1 year was 12.8 ± 1.19 for the test group and 12.5 ± 1.36 for the control group (p = .362). MBML difference between baseline (after final crown delivery) and the 1-year follow-up was gain of 0.2 ± 1.02 mm for the test group (p = .047) and no change in the control group. CBC after 1 year were 0.1 mm ± 0.21 mm (mesial) and 0.2 mm ± 0.22 mm (distal) for the test group and 0.2 mm ± 0.25 mm (mesial) and 0.3 mm ± 0.19 mm (distal) for the control group, p = .540 (mesial) and p = .462 (distal). Test group required half the chair time (127 ± 13 min) when compared to the control group (259 ± 15 min, p < .001). CONCLUSIONS: Within the limits of this trial, both treatment protocols resulted in excellent esthetic outcomes with PES >12 after 1-year follow-up.

Periosteum-Derived Mesenchymal Stem Cells Secretome - Cell-Free Strategy for Endogenous Bone Regeneration: Proteomic Analysis in Vitro.

OBJECTIVES: Millions of people worldwide are affected by diseases or injuries which lead to bone/tooth loss and defects. While such clinical situations are daily practice in most of the hospitals, the widely used treatment methods still have disadvantages. Therefore, this field of medicine is actively searching new tissue regeneration techniques, one of which could be stem cell secretome. Thus, the purpose of this research study was to perform the detail proteomic analysis of periosteum-derived mesenchymal stem cells secretome in order to evaluate if it is capable to induce osteo-regenerative process. MATERIAL AND METHODS: Periosteum-derived mesenchymal stem cells (PMSCs) were extracted from adult male New Zealand White rabbits. Cells were characterised by evaluating their differentiation potential. After characterisation PMSCs secretomes were collected and their proteomic analysis was performed. RESULTS: PMSCs were extracted from adult male New Zealand White rabbits. In order to characterise the extracted PMSCs, they were differentiated in the directions which mainly describes MSC multipotency - osteogenic, myogenic and adipogenic. A total of 146 proteins were detected. After characterisation PMSCs secretomes were collected and their proteomic analysis was performed. The resulting protein composition indicates the ability to promote bone regeneration to fully mature bone. CONCLUSIONS: Bioactive molecules detected in periosteum-derived mesenchymal stem cells secretome initiates the processes required for the formation of a fully functional bone.

Assessment of the Bone Healing Process Mediated by Periosteum-Derived Mesenchymal Stem Cells' Secretome and a Xenogenic Bioceramic-An In Vivo Study in the Rabbit Critical Size Calvarial Defect Model.

The mesenchymal stem cell (MSC) secretome has been considered an innovative therapeutic biological approach, able to modulate cellular crosstalk and functionality for enhanced tissue repair and regeneration. This study aims to evaluate the functionality of the secretome isolated from periosteum-derived MSCs, from either basal or osteogenic-induced conditions, in the healing of a critical size calvarial bone defect in the rabbit model. A bioceramic xenograft was used as the vehicle for secretome delivery, and the biological response to the established biocomposite system was assessed by clinical, histological, histomorphometric, and microtomographic analysis. A comparative analysis revealed that the osteogenic-induced secretome presented an increased diversity of proteins, with emphasis on those related to osteogenesis. Microtomographic and histological morphometric analysis revealed that bioceramic xenografts implanted with secretomes enhanced the new bone formation process, with the osteogenic-induced secretome inducing the highest bone tissue formation. The application of the MSC secretome, particularly from osteogenic-induced populations, may be regarded as an effective therapeutic approach to enhance bone tissue healing and regeneration.

Extraction Socket Preservation Using Growth Factors and Stem Cells: a Systematic Review.

OBJECTIVES: To evaluate the reported literature on the use of stem cells or growth factors for post extraction treatment of the alveolar bone. MATERIAL AND METHODS: A NCBI PubMed and PubMed Central databases search was conducted between September 2010 and August 2018, to identify animal or clinical studies reporting the clinical, radiographical and/or histological outcomes of socket preservation techniques after applying mesenchymal stem cells or growth factors. Only studies published in English language in the last 10 years were included in the study. RESULTS: Eleven studies were identified fulfilling the inclusion criteria. They evaluate a total of 386 post extraction sockets. The main tested materials identified in the current review were bone morphogenetic protein-2 - 3 studies and mesenchymal stem cells - 3 studies. Other comparators were bone morphogenetic protein-9, platelet-derived growth factor-BB homodimers and bone marrow. Overall evaluation indicate positive results for all test groups showing differences in final socket width between 0.64 and 1.28 mm favouring the test groups. Histologically, no particular differences are detected between test and control groups. Most of the studies present low risk of bias. CONCLUSIONS: In general, the use of mesenchymal stem cells or bioactive osteogenic molecules favours bone regeneration after tooth extraction, as evaluated clinically, radiographically and histologically. However, specific differences that support particular recommendations are still unclear in light of the current published evidence. Future studies should include the standardization of the mesenchymal stem cells selection and purification as well as dosage and delivery methods of bioactive molecules.

The 2nd Baltic Osseointegration Academy and Lithuanian University of Health Sciences Consensus Conference 2019. Summary and Consensus Statements: Group II - Extraction Socket Preservation Methods and Dental Implant Placement Outcomes within Grafted Sockets.

INTRODUCTION: The task of Group II was to review and update the existing data concerning extraction socket preservation with or without membranes and soft tissue influence on post-extraction alveolar ridge preservation; extraction socket preservation using different biomaterials as bone grafts, growth factors, and stem cells. Special interest was paid to the dental implant placement outcomes within grafted sockets. MATERIAL AND METHODS: The main areas evaluated by this group were as follows: quantitative and qualitative assessment of the effect of different alveolar preservation techniques performed immediately after tooth extraction, with or without membranes and/or soft tissue grafting, and the use of different bone substitutes, stem cells or growth factors in the postextraction socket. Evaluation of the treatment outcomes of dental implants placed in the grafted sockets in terms of primary and secondary outcomes were assessed. The systematic reviews and/or meta-analyses were registered in PROSPERO, an international prospective register of systematic reviews: http://www.crd.york.ac.uk/PROSPERO/. TThe literature in the corresponding areas of interest was screened and reported following the PRISMA guidelines (Preferred Reporting Item for Systematic Review and Meta-Analysis) Statement: http://www.prisma-statement.org/. Method of preparation of the systematic reviews, based on comprehensive search strategies, was discussed and standardized. The summary of the materials and methods employed by the authors in preparing the systematic reviews and/or meta-analyses is presented in the Preface chapter. RESULTS: The results and conclusions of the review process are presented in the respective papers. Three systematic reviews and one systematic review and meta-analysis were performed. The group's general commentaries, consensus statements, clinical recommendations and implications for research are presented in this article.

Use of Autologous Stem Cells for the Regeneration of Periodontal Defects in Animal Studies: a Systematic Review and Meta-Analysis.

OBJECTIVES: To overview preclinical animal trials and quantify the effect size that stem cell therapy has on the regeneration of periodontal tissue complex. MATERIAL AND METHODS: A systematic MEDLINE (PubMed) online library search was conducted for preclinical animal studies in vivo , using autologous periodontal ligament, dental pulp, cementum, alveolar periosteal, gingival margin or adipose stem cell types for periodontal tissue complex regeneration purposes. Studies had to be published between 2007.09.01 and 2017.09.01 in the English language. RESULTS: Online library search yielded 2099 results. After the title, abstract and full-text screening ten studies fit inclusion criteria and were pooled into meta-analysis. Overall the stem cell regenerative therapy had a statistically significant positive influence on the periodontal tissue regeneration when compared to the control groups. The biggest influence was made to the regeneration of cementum (standardised mean difference [SMD] 2.25 [95% confidence interval (CI) = 1.31 to 3.2]) while the smallest influence was made to the alveolar bone (SMD 1.47 [95% CI = 0.7 to 2.25]) the effect size for periodontal ligament regeneration was (SMD 1.8 [95% CI = 1 to 2.59]). Subgroup analysis showed statistically significant (P < 0.05) differences between different cell types in the alveolar bone and cementum regeneration groups and in alveolar bone group in relation to scaffold materials. CONCLUSIONS: Stem cell therapy has a positive impact on periodontal tissue complex regeneration. Such therapy has the biggest influence on cementum regeneration meanwhile alveolar bone regeneration is influenced by the least amount. However more and less diverse preclinical studies are needed to have a greater statistical power in future meta-analyses.

Cuttlebone as a Marine-Derived Material for Preparing Bone Grafts.

The use of synthetic materials for biomedical applications still presents issues owing to the potential for unfavourable safety characteristics. Currently, there is increasing interest in using natural, marine-derived raw materials for bone tissue engineering. In our study, the endoskeleton of the mollusc Sepia, i.e. cuttlebone (CB), was used with regenerated cellulose (RC) to prepare three-dimensional composite bone grafts. CB microparticles were mechanically immobilised within a cellulose gel, resulting in a macroporous structure upon lyophilisation. The interconnected porous structure of the regenerated cellulose/cuttlebone (RC/CB) composite was evaluated by micro-computed tomography. The porosity of the composite was 80%, and the pore size predominantly ranged from 200 to 500 µm. The addition of CB microparticles increased the specific scaffold surface by almost threefold and was found to be approximately 40 mm-1. The modulus of elasticity and compressive strength of the RC/CB composite were 4.0 ± 0.6 and 22.0 ± 0.9 MPa, respectively. The biocompatibility of the prepared RC/CB composite with rat hepatocytes and extensor digitorum longus muscle tissue was evaluated. The obtained data demonstrated that both the composite and cellulose matrix samples were non-cytotoxic and had no damaging effects. These results indicate that this RC/CB composite is a novel material suitable for bone tissue-engineering applications.

Novel cellulose/hydroxyapatite scaffolds for bone tissue regeneration: In vitro and in vivo study.

Cellulose scaffolds containing nano- or micro-hydroxyapatite (nHA or µHA) were prepared by the regeneration of cellulose from its acetylated derivative and the mechanical immobilization of inorganic particles, followed by freeze-drying. Microtomographic (micro-computed tomography) evaluation revealed that both scaffolds presented a highly interconnected porous structure, with a mean pore diameter of 490 ± 94 and 540 ± 132 µm for cellulose/nHA and cellulose/µHA, respectively. In vitro and in vivo characterizations of the developed scaffolds were investigated. Commercially available bone allograft was used as a control material. For the in vitro characterization, osteoblastic cell cultures were used and characterized over time to evaluate cell adhesion, metabolic activity, and functional output (alkaline phosphatase activity and osteoblastic gene expression). The results revealed greater spreading cell distribution alongside an increased number of filopodia, higher MTT values, and significantly increased expression of osteoblastic genes (Runx-2, alkaline phosphatase, and BMP-2) for cellulose/nHA, compared with cellulose/µHA and the control. The in vivo biocompatibility was evaluated in a rabbit calvarial defect model. The investigated scaffolds were implanted in circular rabbit calvaria defects. Four- and 12-week bone biopsies were investigated using micro-computed tomography and histological analysis. Although both cellulose/HA scaffolds outperformed the assayed control, a significantly higher amount of newly formed mineralized tissue was found within the defects loaded with cellulose/nHA. Within the limitations of this study, the developed cellulose/HA scaffolds showed promising results for bone regeneration applications. The biological response to the scaffold seems to be greatly dependent on the HA particles' characteristics, with cellulose scaffolds loaded with nHA eliciting an enhanced bone response.

Influence of Peri-Implant Soft Tissue Condition and Plaque Accumulation on Peri-Implantitis: a Systematic Review.

OBJECTIVES: To systematically examine influence of soft tissue condition and plaque accumulation around dental implants on peri-implantitis development. MATERIAL AND METHODS: An electronic literature search was conducted of two databases - MEDLINE (Ovid) and EMBASE from 2011 to 2016. Sequential screenings at the title, abstract, and full-text levels were performed. Clinical human studies in the English language that had reported soft tissue condition or plaque accumulation influence on peri-implantitis development were included. The resulting articles were independently subjected to clear inclusion and exclusion criteria by two reviewers as follows. RESULTS: The search resulted in 8 articles meeting the inclusion criteria. These studies reported gingival index, plaque index, pocket depth, bleeding on probing/modified bleeding index for sites with "adequate" (≥ 2 mm) and "inadequate" (< 2 mm) width of keratinized mucosa. Results demonstrated that the amount of keratinized mucosa has little influence on soft-tissue inflammation in the presence of good oral hygiene. However, suboptimal oral hygiene due to difficulty in access for plaque control in the areas of minimal keratinized mucosa may lead to greater tissue damage. CONCLUSIONS: In cases with insufficient keratinized gingiva in the vicinity of implants, the insufficiency does not necessarily mediate adverse effects on the hygiene management and soft tissue health condition. Nonetheless, the risk of the increase of gingival index, plaque index, pocket depth, bleeding on probing/modified bleeding index is present. Therefore, the presence of an appropriate amount of keratinized gingiva is required.

The 1st Baltic Osseointegration Academy and Lithuanian University of Health Sciences Consensus Conference 2016. Summary and Consensus Statements: Group I - Peri-Implantitis Aetiology, Risk Factors and Pathogenesis.

INTRODUCTION: The task of Group 1 was to review and update the existing data concerning aetiology, risk factors and pathogenesis of peri-implantitis. Previous history of periodontitis, poor oral hygiene, smoking and presence of general diseases have been considered among the aetiological risk factors for the onset of peri-implant pathologies, while late dental implant failures are commonly associated with peri-implantitis and/or with the application of incorrect biomechanical forces. Special interest was paid to the bone cells dynamics as part of the pathogenesis of peri-implantitis. MATERIAL AND METHODS: The main areas indagated by this group were as follows: influence of smoking, history of periodontitis and general diseases on peri-implantitis development, bio-mechanics of implant loading and its influence on peri-implant bone and cellular dynamics related to the pathogenesis of peri-implantitis. The systematic reviews and/or meta-analyses were registered in PROSPERO, an international prospective register of systematic reviews: http://www.crd.york.ac.uk/PROSPERO/. The literature in the corresponding areas of interest was screened and reported following the PRISMA (Preferred Reporting Item for Systematic Review and Meta-Analysis) Statement: http://www.prisma-statement.org/. Method of preparation of the systematic reviews, based on comprehensive search strategies, was discussed and standardized. The summary of the materials and methods employed by the authors in preparing the systematic reviews and/or meta-analyses is presented in Preface chapter. RESULTS: The results and conclusions of the review process are presented in the respective papers. One systematic review with meta-analysis, three systematic reviews and one theoretical analysis were performed. The group's general commentaries, consensus statements, clinical recommendations and implications for research are presented in this article.