Systematic review on the association between genetic polymorphisms and dental implant-related biological complications.

OBJECTIVES: The aim of this systematic review was to evaluate the association between specific genetic polymorphisms and dental implant-related biological complications in patients having a follow-up period of at least 12-months post-loading. MATERIAL AND METHODS: A sensitive search strategy was developed to identify implant-related genetic-association studies. This was performed by searching five databases. A three-stage screening (titles, abstract, full text) was carried out in duplicate and independently by two reviewers. Assessment was carried out according to the suggested scale for quality assessment of periodontal genetic-association studies and adapted to genetic analyses of implant-related studies leading to an overall final score 0-20 based on the summation of positive answers. RESULTS: The initial search resulted in 1838 articles. Sixty-seven full-text articles were assessed for eligibility and four studies met the defined inclusion criteria. IL-6 G174C, TNF-α -308, IL-1A-889 and IL-1B+3954 and CD14-159 C/T polymorphisms were evaluated. The quality assessment scores ranged from 6 to 11 positive answers from out of a maximum score of 20. The great heterogeneity among the studies did not allow a meta-analysis. CONCLUSIONS: The published evidence on genetic predisposition and implant biologic complications is limited. The small number of identified studies evaluating the association between genetic polymorphisms and peri-implant disease presented methodological and reporting inadequacies. Thus, the potential link between genetic polymorphisms and biological complications should be further investigated and clarified through well-designed clinical studies on adequately powered and appropriately included study populations.

The role of strontium ranelate and guided bone regeneration in osteoporotic and healthy conditions.

BACKGROUND/ OBJECTIVES: SR is a chemical agent developed for the treatment of osteoporosis. In vitro, SR enhanced replication of osteoprogenitor cells and bone formation. In vivo, in ovariectomized rats SR prevented the biomechanical deterioration of bone while in non-ovariectomized rats, enhanced bone architecture and increased trabecular and cortical bone mass. The aim of this study was to evaluate the effect of SR on bone healing of calvarial critical size defects treated with a deproteinized bovine bone mineral (DBBM) and a collagen barrier (CM), in healthy and osteoporotic rats. MATERIAL AND METHODS: Sixty-four, 4-month-old Wistar female rats were used. Osteoporosis was induced by ovariectomy and calcium-deficient diet in half of them. Sixteen ovariectomized (OSR) and 16 healthy (HSR) rats were treated with SR while no medication was administered in the remaining 16 healthy (H) and 16 ovariectomized (O) rats. At 6 weeks after ovariectomy, a 5mm defect was created in each parietal bone of every animal. One defect was treated with DBBM and CM, while the contralateral was left untreated. Qualitative and quantitative histological analysis was performed at 30 and 60 days of healing. A generalized estimating equations test was performed to evaluate the effect of SR and osteoporosis, on new bone formation (NB). RESULTS: After 30 days of healing, NB in the untreated defects was 3.4%±1.7%, 4.3%±6.2%, 3.2±4.5%, 15.9±23.5% in O, OSR, H and HSR groups, respectively; after 60 days, NB was 4.7%±4.3%, 11.3%±7%, 7.1%±13.2, 12.1%±13.5%, respectively. In the GBR-treated defects, after 30 days, NB was 2.6%±1.4%, 2.4%±1.6%, 4.5%±4.1%, 10.3%±14.4% in O, OSR, H and HSR groups, respectively; after 60 days, NB was 2.2%±1.6%, 4.3%±4.2%, 7%±5.1%, 10.8%±17.4%, respectively. Osteoporosis (p=0.008) and the absence of strontium ranelate treatment (p=0.01) had a negative impact on NB. CONCLUSION: SR may promote bone formation in calvarial defects in healthy and osteoporotic rats, albeit in a moderate extent.

The use of bioactive factors to enhance bone regeneration: A narrative review.

AIM: This review critically appraises the available knowledge on the pre-clinical and clinical use of bioactive factors for bone regeneration in the cranial and maxillofacial area. MATERIALS AND METHODS: The use of growth factors, amelogenins and autologous platelet concentrates (APCs) for bone regeneration was reviewed in a systematic manner. More specifically, pre-clinical and clinical studies on ridge preservation, alveolar ridge augmentation, regeneration of peri-implant defects and sinus augmentation models were considered. RESULTS: Amongst different bioactive factors, the highest pre-clinical and clinical evidence of a positive effect on bone formation is associated with rhBMP-2 and the lowest with amelogenins. While APCs seem to accelerate clinical healing and reduce postoperative discomfort, there is insufficient and contrasting evidence of a significant effect on hard tissue regeneration for the different clinical applications. CONCLUSIONS: Although there is increasing evidence that bioactive factors might enhance the bone regeneration process, the great heterogeneity of the available studies and the limited number of RCTs do not allow to draw robust conclusions. Issues that still need to be investigated include the optimal carriers for bioactive agents (direct vs. indirect), the dosage, the timing of administration, as well as the possibility of combining different agents to promote synergistic effects.

Description of the periodontal pocket in preclinical models: limitations and considerations.

Establishment of periodontal health and regeneration of the lost periodontal tissues are always the ultimate goal of periodontal treatment. The development of new therapeutic approaches raises the necessity for appropriate experimental models that present periodontal structures and healing capability comparable to humans. Preclinical research and extrapolation of the data to human conditions remains a stage of great importance before the clinical application of the new biomaterials and techniques. Periodontal pockets/defects in preclinical models can be induced experimentally through acute or chronic or a combination of both (induced) modalities. The features of the created defects and those of humans vary greatly mostly due to the nature of the periodontal disease. This is an important point to take into account, since it is well recognized that the potential of periodontal therapy may be dependent on both the biological background and the defect morphology. This review provides insight into the commonly used preclinical models for the reproduction of the periodontal pocket and discusses the advantages and disadvantages of each model in terms of similarity to human conditions, standardization and reproducibility.

The effect of experimental osteoporosis on bone regeneration: Part 1, histology findings.

OBJECTIVES: To histologically define the healing events occurring in calvarial critical size defects (CSDs) following treatment with a collagen barrier for guided bone regeneration (GBR) and a particulate graft in healthy and osteoporotic conditions. MATERIAL AND METHODS: Thirty-six 10-month-old, female, Wistar rats were used in this study. Half of them were ovariectomized (OVX) and fed with a low-calcium diet to induce an osteoporotic-like status. In each animal of both groups, two 5-mm CSDs were created, one in the centre of each parietal bone, and they were treated with a deproteinized bovine bone mineral (DBBM) particulate graft and a bi-layer collagen membrane. Six OVX and six healthy control rats were randomly euthanized at 7, 14 and 30 days. One defect per animal was randomly processed for decalcified histology. Three central sections were used for qualitative histology and histomorphometric analysis. RESULTS: No significant difference in terms of percentage of newly formed bone was detected between the two groups at the different healing periods. However, a trend towards less bone formation and of poorer quality, expressed as reduced bone maturation, was detected in the OVX animals at 30 days. DISCUSSION: According to this study, GBR with a collagen barrier and a DBBM graft can be successfully obtained also in osteoporotic-like conditions. Future studies considering longer healing periods and controlling for the confounding factors arising from the use of a particulate graft are needed to confirm these data.

Experimental models for guided bone regeneration in healthy and medically compromised conditions.

The increased use of dental implants and related bone-augmentation procedures creates a need for reliable proof-of-principle preclinical models for evaluating different bone-regenerative techniques. The simulation of clinical scenarios by such models is of importance when the experiments are designed in order for the outcomes to provide basic points of clinical relevance. At the same time, the increased proportion of the population with different chronic diseases of ageing necessitates the need to reproduce these conditions in the same proof-of-principle preclinical models to allow evaluation of the effect of the relevant chronic disease on the bone-healing process. This review presents a number of 'proof-of-principle' preclinical models in health and in chronic systemic conditions in which the guided bone regeneration principle was evaluated.

Survival Rates of Short Dental Implants (≤6 mm) Used as an Alternative to Longer (>6 mm) Implants for the Rehabilitation of Posterior Partial Edentulism: A Systematic Review of RCTs.

Short dental implants have been proposed as an alternative treatment option to bone regeneration procedures for the rehabilitation of resorbed alveolar ridges. The aim of this paper was to systematically review randomized controlled trials (RCTs) comparing short implants (≤6 mm) and longer implants (>6 mm) in atrophic alveolar ridges in terms of implant survival rates, peri-implant marginal bone loss (MBL), prevalence of peri-implantitis and technical complications. A thorough electronic search was performed until September 2023. RCTs with follow-up of at least 1-year post-loading comparing short implants with rough surfaces to longer implants in the posterior jaws of systemically and periodontally healthy, partially edentulous adults were considered. Studies with incomplete information on the number of patients, follow-up or definition of "short implants" were excluded. The revised Cochrane risk-of-bias tool for randomized trials was used for Risk of bias assessment. Fixed-effects meta-analysis of the selected studies was applied to compare the outcome variables. Random-effect meta-analysis was performed, on the basis of within-study comparisons. In total, 16 articles were selected for meta-analysis and incorporated 408 short implants and 475 longer implants inserted in 317 and 388 patients, respectively. The survival rates of longer implants in pristine or augmented bone were significantly increased compared to short implants (95%CI: 2-5%, p < 0.001). Standard-length implants displayed increased, although non-statistically significant MBL (95%CI: -0.17-0.04, p > 0.05), and prevalence of peri-implantitis (95%CI: 0-5%, p > 0.05). No statistically significant differences were observed between short and long implants in terms of technical complications (implant-level 95%CI: -4-6%, p > 0.05). Short implants represent a promising alternative treatment option for the rehabilitation of posterior jaws to avoid additional bone augmentation procedures. Nonetheless, they should be selected cautiously due to a potentially limited survival rate compared to longer implants. A major limitation of this study is the variability in the included studies regarding sample size, patient profile, type of bone, loading protocol, definition of peri-implantitis, among others. This study received no external funding. The study protocol was registered in PROSPERO (CRD42023485514).

Recent Advances in Scaffolds for Guided Bone Regeneration.

The rehabilitation of alveolar bone defects of moderate to severe size is often challenging. Currently, the therapeutic approaches used include, among others, the guided bone regeneration technique combined with various bone grafts. Although these techniques are widely applied, several limitations and complications have been reported such as morbidity, suboptimal graft/membrane resorption rate, low structural integrity, and dimensional stability. Thus, the development of biomimetic scaffolds with tailor-made characteristics that can modulate cell and tissue interaction may be a promising tool. This article presents a critical consideration in scaffold's design and development while also providing information on various fabrication methods of these nanosystems. Their utilization as delivery systems will also be mentioned.

A systematic review on the association between genetic predisposition and dental implant biological complications.

OBJECTIVES: The aim of this systematic review was to evaluate the relationship between genetic polymorphisms and dental implant biological complications. MATERIAL AND METHODS: All prospective, cross-sectional and retrospective studies reporting on dental implant loss/peri-implantitis/peri-implant marginal bone loss after loading in association with genetic polymorphism were considered for inclusion. A thorough search of electronic databases, supplemented by checking bibliographies of review articles was performed by two independent reviewers. Quality assessment of the included studies was conducted independently and in duplicate by two reviewers as part of the data extraction process. RESULTS: The search provided 344 related articles. Twenty-two publications were identified for possible inclusion and finally, seven articles met the defined inclusion criteria. Four studies which investigated the potential relationship between early implant loss and IL-1, IL-2, IL-6, TNF-α or TGF-ß1 genotype revealed no evidence to support this association. In two of the three studies which evaluated peri-implantitis in relation to IL-1 genotype, the findings indicate that IL-1RN (intron 2), IL-1A (-899), IL-1B (+3954) gene polymorphisms were correlated to increased peri-implant tissue infection and destruction. CONCLUSIONS: Methodological and study design issues restricted the possibility to draw robust conclusions. Within the limits of this review, it might be concluded that there is no obvious association between specific genetic polymorphism and dental implant failure in terms of biological complications, although a tendency should be underlined showing the potential link between IL-1 genotype and peri-implantitis. Well designed and adequately powered prospective cohort studies are needed to provide further information.

Minimally invasive surgical techniques for the treatment of different types of isolated intrabony defects: A narrative review.

The aim of this literature review was to present minimally invasive surgical techniques (MISTs) for the regeneration of intrabony defects and the impact of these surgical procedures on clinical outcomes. Less invasive surgical procedures lead to a more uneventful postoperative healing and reduce patient morbidity. The introduction of these techniques together with the use of magnification tools enables gentle tissue manipulation with performing minimal incisions and flap elevations in the field of surgical treatment of intrabony defects. Minimally invasive surgical techniques induce minor surgical trauma and improve the wound stability with favorable results in terms of clinical outcomes and the patient's comfort. The defect anatomy, patient-centered factors and the various biomaterials applied are considered. Recent evidence concludes that the adjunctive use of regenerative materials seems to have a less determinant effect on the clinical performance of minimally invasive surgical techniques. In addition, more studies are required to investigate the clinical efficacy of these surgical techniques in the treatment of intrabony defects in comparison with the conventional papilla preservation flap techniques.

A randomized, controlled trial on the effect of non-surgical periodontal therapy in patients with type 2 diabetes. Part I: effect on periodontal status and glycaemic control.

AIM: the purpose of the present study was to assess the effect of non-surgical periodontal therapy on glycaemic control of type 2 diabetes patients with moderate-to-severe periodontitis. MATERIALS AND METHODS: this was a randomized, controlled clinical trial of patients with type 2 diabetes. A total of 60 patients with moderate-to-severe periodontal disease were assigned to either a periodontal treatment arm, consisting of scaling and root planing (intervention group [IG]), or a delayed treatment arm that received periodontal care after 6 months (control group [CG]). Periodontal parameters and glycosylated haemoglobin (A1C) were evaluated at 1, 3 and 6 months. RESULTS: all periodontal parameters improved significantly in the IG. A1C levels decreased statistically significantly more in the IG versus the CG (0.72%versus 0.13%; p<0.01) independently of other confounders. CONCLUSIONS: this study provides evidence that periodontal treatment contributes to improved glycaemic control in type 2 diabetes mellitus patients. Larger controlled trials are needed to confirm if this finding is generalizable to other populations of patients with type 2 diabetes.

Platelet-rich plasma effect on periodontally affected human gingival fibroblasts: an in vitro study.

OBJECTIVE: The purpose of this study was to evaluate the gingival fibroblast proliferative response derived from patients with chronic and aggressive periodontitis to homologous platelet-rich plasma (PRP). MATERIALS AND METHODS: Gingival fibroblasts derived from nine patients with chronic periodontitis, aggressive periodontitis and healthy periodontium were grown. Medium was replaced with DMEM containing 0.5% FBS in which cells remained for two days. Cells were incubated and cultured with medium containing 50 microl/ml homologous platelet-rich plasma (PRP) or not containing PRP (control) for 24 and 48 hours. PRP originated from three donors. Cell proliferation effect was evaluated at 24 and 48 hours. Cell viability was assessed with a hemocytometer. Viable cells were counted under a phase contrast microscope. RESULTS: The results revealed that incubation of human gingival fibroblasts, derived from healthy and intact periodontium, chronic periodontitis and aggressive periodontitis, in culture medium containing homologous PRP statistically significantly increased the cell proliferation at 24 and 48 hours of culture. CONCLUSION: The addition of PRP to human gingival fibroblast cultures significantly increased the proliferative response, irrespective of the presence of periodontitis, type of periodontitis and PRP donor.

Efficacy of probiotics: clinical and microbial parameters of halitosis.

BACKGROUND & AIM: Halitosis is defined as an offensive breath odour of whatever source and therefore may affect a person's social interactions. Intra-oral halitosis is a result of bacterial activity. Therefore, probiotics may offer an appropriate and biological solution as a part of the therapy of intra-oral halitosis. The aim of this systematic review was to study the effect of the administration of probiotics alone or as an adjunct to other treatments on the level of halitosis as measured by volatile sulphur compound (VSC) levels, organoleptic scores (ORG) or hydrogen sulphide, methyl mercaptan and dimethyl sulphide levels. In addition, the effect of probiotic usage on oral microbial composition was summarised. METHODS: The MEDLINE-PubMed and Embase databases were searched up to September 2017 with language restricted to English. Eligible papers were selected according to pre-set criteria; the data was extracted and analysed descriptively. RESULTS: The search resulted in 1104 original research articles and a final six were selected as being eligible including 129 subjects. These studies used different detection methods and combinations thereof to measure halitosis. Five studies were randomised placebo-controlled clinical trials of which two studies reported a significant reduction in ORG between probiotic and placebo groups, and two studies on the basis of total VSC levels. The two studies reporting a significant improvement in ORG did not find an improvement in total VSC levels. Three studies included a microbiological assessment. In these three studies, the probiotic strain was detected at the end of the treatment period, but no detailed data was reported on the abundance of the strain before and after the treatment period. CONCLUSIONS: Probiotics may be beneficial in treating intra-oral halitosis. However, due to limited data and the heterogeneity of the studies, the efficacy of probiotics remains unclear. Studies with more subjects and standardised protocols need to be designed.

Experimental model for bone regeneration in oral and cranio-maxillo-facial surgery.

Bone and tooth loss, as a result of trauma, anatomical or congenital reasons, cancer, and periodontal disease, is a common therapeutic problem in the fields of cranio-maxillo-facial surgery and periodontics. The proposed techniques for the treatment of various bone defects encountered include bone grafts, bone substitutes, guided tissue regeneration, and distraction osteogenesis as well as their combinations. In addition, dental implants have been successfully utilized for the restoration of full or partial edentulism. The introduction and development of new therapeutic approaches and devices demand the use of appropriate animal models that present bone anatomy and healing comparable to human. Among other animal models, the pig is extensively documented in several biomedical areas and has been largely used in maxillo-facial surgery and implants dentistry-related research. Anatomical and physiological similarities with human in size, physiology, and bone biology contribute to a successful involvement of this animal to understand and treat various osseous lesions. However, improvements and standardization are requested with respect to consistency and discrimination abilities. The aim of this review is to provide a critical appraisal of the literature related to swine models for the evaluation of cranio-maxillo-facial osseous defect healing, regeneration, and bone-implant interface. This review should assist researchers in the field to select the most appropriate model for each dedicated purpose and also contribute to stimulate an innovative thinking on the use of porcine models.

Effect of non-surgical periodontal therapy on C-reactive protein, oxidative stress, and matrix metalloproteinase (MMP)-9 and MMP-2 levels in patients with type 2 diabetes: a randomized controlled study.

BACKGROUND: It is well accepted that glycemic control in patients with diabetes mellitus (DM) is affected by systemic inflammation and oxidative stress. The effect of periodontal therapy on these systemic factors may be related to improvement on glycemic status. The aim of the present study is to assess over a period of 6 months the effect of non-surgical periodontal therapy on serum levels of high-sensitivity C-reactive protein (hsCRP), d-8-iso prostaglandin F2a (d-8-iso) as a marker of oxidative stress, and matrix metalloproteinase (MMP)-2 and MMP-9 on patients with type 2 DM. METHODS: Sixty participants with type 2 DM and moderate to severe periodontal disease were randomized into intervention (IG) and control (CG) groups. IG received scaling and root planing, whereas CG received supragingival cleaning at baseline and scaling and root planing at 6 months. Participants of both groups were evaluated at baseline and 1, 3, and 6 months. Periodontal data recorded at each visit included probing depth, clinical attachment loss, bleeding on probing, and gingival index. Blood was collected at each visit for the assay of serum glycated hemoglobin A1c (A1c), hsCRP, d-8-iso, MMP-2, and MMP-9. RESULTS: Although there was a trend to a reduction in hsCRP, d-8-iso and MMP-9 it did not reach statistical significance. MMP-2 levels remained unchanged after periodontal treatment. CONCLUSION: Effective non-surgical periodontal treatment of participants with type 2 DM and moderate to severe periodontal disease improved significantly A1c levels but did not result in a statistically significant improvement in hsCRP, d-8-iso, MMP-2, and MMP-9 levels.

RANKL and OPG mRNA level after non-surgical periodontal treatment.

Recent research evidence shows that the receptor activator of nuclear factor-kappa B ligand (RANKL) and osteoprotegerin (OPG) play an important role in osteoclastogenesis and the inflammatory bone loss during periodontitis. Bone remodeling process is dependent on the balance of these two proteins while a high ratio of RANKL/OPG characterizes the increased osteolytic process and it has been reported in inflammatory diseases including the periodontal disease. The purpose of this study was to determine the OPG and RANKL mRNA levels in periodontal tissues derived from patients with advanced chronic periodontitis after non-surgical periodontal therapy (SRP) and to compare the RANKL/OPG ration with that in healthy persons. Gingival biopsies were obtained from subjects with clinically healthy periodontium (H) (N = 11) and patients with advanced chronic periodontitis (CP) (N = 14). Total RNA was isolated from the gingival samples and 1 microg RNA was reverse transcribed to cDNA, followed by polymerase chain reaction (PCR) using specific primers for OPG and RANKL. The efficiency of reverse transcription was verified by the amplification of the GAPDH gene. The intensity of RT-PCR products was analyzed by a densitometer and was normalized to the intensity of the band for the housekeeping gene GAPDH. Immunohistochemical evaluation of the RANKL and OPG expression was also performed. The expression of RANKL as well as of OPG was reduced in CP specimens in comparison to that of healthy persons in a statistical significant way. However, the RANKL/OPG ratio showed to be slightly elevated in CP compared to H specimens but this finding was not of statistical significance. The immunohistochemical analysis revealed a non-uniform expression pattern for both proteins. Although further investigation is needed to identify the specific role of RANKL and OPG protein in periodontitis progression, our data after SRP might indicate the possible involvement of these proteins in the activation of pathways, which regulate the repair of the periodontal tissues.

Time- and dose-dependent mitogenic effect of basic fibroblast growth factor combined with different bone graft materials: an in vitro study.

OBJECTIVES: In periodontal regeneration, the growth factor concentrations and the delivery system used are of great importance. In an attempt to assess the mitogenic effect of basic fibroblast growth factor (bFGF) on periodontal ligament (PDL) cells combined with different bone replacement materials, two allografts of cortical (DFDBA) and cancellous (DFBA) bone and an anorganic bovine material with a synthetic peptide (ABM P-15) were used. The purpose of this study was to evaluate the in vitro mitogenic effect of different doses of bFGF alone or in combination with DFDBA, DFBA and ABM P-15 on human PDL cells in a time-dependent mode. MATERIAL AND METHODS: PDL cell cultures were derived from the mid-root of four maxillary premolars. Cells were grown and reached confluence. On day 2 of quiescence, new medium was added along with (1) 1, 5, 10 and 25 ng/ml of bFGF alone, (2) 10 mg of DFDBA, DFBA and ABM P-15 alone and (3) their combination. The mitogenic effect was determined at 24 and 48 h of culture by using a hemocytometer chamber. The cells were counted under a phase contrast microscope. RESULTS: The results revealed that bFGF at the highest concentrations and after 48 h exerted a significant mitogenic effect on PDL cells, and also DFDBA and DFBA supported cell proliferation. Furthermore, DFDBA and DFBA enriched with bFGF had a significant mitogenic effect after 48 h of culture. ABM P-15 with 10 and 25 ng/ml of bFGF up-regulated PDL cell proliferation after 48 h of incubation. CONCLUSIONS: The findings of this study demonstrate the beneficial role of bFGF combined with DFDBA and DFBA as carriers in periodontal repair.