Effect of doxycycline doped nanoparticles on osteogenic/cementogenic and anti-inflammatory responses of human cells derived from the periodontal ligament.

OBJECTIVES: This work aimed to evaluate if doxycycline-doped polymeric nanoparticles possessed any anti-inflammatory effect and promote osteogenic/cementogenic differentiation of stem cells from human periodontal ligament (PDLSCs). METHODS: The polymeric nanoparticles (NPs) were produced by a polymerization/precipitation process and doped with doxycycline (Dox-NPs). PDLSCs were cultured in the presence or absence of the NPs under osteogenic medium or IL-1ß treatment. Cells' differentiation was assessed by gene expression analysis of osteogenic/cementogenic markers alkaline phosphatase (ALP) and Runt-related transcription factor 2 (RUNX2). An anti-inflammatory effect was also ascertained by analyzing IL-1ß gene expression. Adipogenic and chondrogenic differentiation was used to confirm the multipotency of PDLSCs. RESULTS: Gene expression of ALP and RUNX2 in PDLSCs was significantly upregulated by the osteogenic medium (ALP: p<0.001; RUNX2: p = 0.005) while Dox-NPs further enhanced ALP gene expression of PDLSCs treated with the osteogenic medium. Furthermore, Dox-NPs suppressed the up-regulation of IL-1ß when cells were subjected to an inflammatory challenge. CONCLUSIONS: Dox-NPs enhanced PDLSCs differentiation into osteoblasts/cementoblasts lineages while providing an anti-inflammatory effect. CLINICAL SIGNIFICANCE: Due to their biocompatibility as well as anti-inflammatory and osteogenic/cementogenic effects, Dox-NPs are potential candidates for being used in periodontal regeneration.

Dexamethasone-doped nanoparticles improve mineralization, crystallinity and collagen structure of human dentin.

OBJECTIVES: Bioactive materials have been used for functionalization of adhesives to promote dentin remineralization. This study aims to evaluate bonding ability and both mechanical and chemical behavior of demineralized dentin infiltrated with polymeric nanoparticles doped with dexamethasone (Dex-NPs). METHODS: Dentin conditioned surfaces were infiltrated with NPs, Dex-NPs or Dex-Zn-NPs. Bonded interfaces were also created and stored for 24 h or 21d, and then submitted to microtensile bond strength testing. Dentin remineralization was analyzed by Nanohardness, Young's modulus and Raman analysis. RESULTS: At 21d of storage, dentin treated with undoped-NPs attained the lowest nanohardness and Young's modulus. Dex-NPs and Zn-Dex-NPs increased dentin nanohardness and Young's modulus after 21d Raman analysis showed high remineralization, crystallinity, crosslinking and better structure of collagen when functionalized Dex-NPs were present at the dentin interface. CONCLUSIONS: Infiltration of dentin with Dex-NPs promoted functional remineralization as proved by nanomechanical and morpho-chemical evaluation tests. Dexamethasone in dentin facilitated crystallographic maturity, crystallinity and improved maturity and secondary structure of dentin collagen. CLINICAL SIGNIFICANCE: Using dexamethasone-functionalized NPs before resin infiltration is a clear option to obtain dentin remineralization, as these NPs produce the reinforcement of the dentin structure, which will lead to the improvement of the longevity of resin restorations.

Dexamethasone and zinc loaded polymeric nanoparticles reinforce and remineralize coronal dentin. A morpho-histological and dynamic-biomechanical study.

OBJECTIVE: To investigate the effect of novel polymeric nanoparticles (NPs) doped with dexamethasone (Dex) on viscoelasticity, crystallinity and ultra-nanostructure of the formed hydroxyapatite after NPs dentin infiltration. METHODS: Undoped-NPs, Dex-doped NPs (Dex-NPs) and zinc-doped-Dex-NPs (Zn-Dex-NPs) were tested at dentin, after 24 h and 21 d. A control group without NPs was included. Coronal dentin surfaces were studied by nano-dynamic mechanical analysis measurements, atomic force microscopy, X-ray diffraction and transmission electron microscopy. Mean and standard deviation were analyzed by ANOVA and Student-Newman-Keuls multiple comparisons (p < 0.05). RESULTS: At 21 d of storage time, both groups doped with Dex exhibited the highest complex, storage and loss moduli among groups. Zn-Dex-NPs and Dex-NPs promoted the highest and lowest tan delta values, respectively. Dex-NPs contributed to increase the fibril diameters of dentin collagen over time. Dentin surfaces treated with Zn-Dex-NPs attained the lowest nano-roughness values, provoked the highest crystallinity, and produced the longest and shortest crystallite and grain size. These new crystals organized with randomly oriented lattices. Dex-NPs induced the highest microstrain. Crystalline and amorphous matter was present in the mineral precipitates of all groups, but Zn and Dex loaded NPs helped to increase crystallinity. SIGNIFICANCE: Dentin treated with Zn-Dex-NPs improved crystallographic and atomic order, providing structural stability, high mechanical performance and tissue maturation. Amorphous content was also present, so high hydroxyapatite solubility, bioactivity and remineralizing activity due to the high ion-rich environment took place in the infiltrated dentin.

Short versus standard implants at sinus augmented sites: a systematic review and meta-analysis.

BACKGROUND: Short implants are proposed as a less invasive alternative with fewer complications than standard implants in combination with sinus lift. The aim of this systematic review and meta-analysis was to state the efficacy of placing short implants (≤ 6 mm) compared to standard-length implants (≥ 8 mm) performing sinus lift techniques in patients with edentulous posterior atrophic jaws. Efficacy will be evaluated through analyzing implant survival (IS) and maintenance of peri-implant bone (MBL). METHODS: Screening process was done using the National Library of Medicine (MEDLINE by PubMed), EMBASE, the Cochrane Oral Health, and Web of Science (WOS). The articles included were randomized controlled trials. Risk of bias was evaluated according to The Cochrane Collaboration's tool. Weighted means were calculated. Heterogeneity was determined using Higgins (I2). A random-effects model was applied. Secondary outcomes such as surgical time, patient satisfaction, mucositis and peri-implantitis, pain, and swelling were analyzed. RESULTS: Fourteen studies (597 patients and 901 implants) were evaluated. IS was 1.02 risk ratio, ranging from 1.00 to 1.05 (CI 95%) (p = 0.09), suggesting that IS was similar when both techniques were used. MBL was higher in patients with standard-length implants plus sinus lift elevation (p = 0.03). MBL was 0.11 (0.01-0.20) mm (p = 0.03) and 0.23 (0.07-0.39) mm (p = 0.005) before and after 1 year of follow-up, respectively, indicating that the marginal bone loss is greater for standard-length implants. DISCUSSION: Within the limitations of the present study, as relatively small sample size, short dental implants can be used as an alternative to standard-length implants plus sinus elevation in cases of atrophic posterior maxilla. Higher MBL was observed in the groups where standard-length implants were used, but implant survival was similar in both groups. Moreover, with short implants, it was observed a reduced postoperative discomfort, minimal invasiveness, shorter treatment time, and reduced costs. CLINICAL CLINICAL RELEVANCE: The low MBL promoted by short implants does contribute to a paradigm shift from sinus grafting with long implants to short implants. Further high-quality long-term studies are required to confirm these findings.

A Systematic Review and Meta-Analysis of Systemic Antibiotic Therapy in the Treatment of Peri-Implantitis.

Research has been conducted into the advantages of the systemic administration of antibiotics. The aim of this systematic review and meta-analysis was to assess the efficacy of systemic antibiotic administration in the treatment of peri-implantitis in terms of bleeding on probing (BoP) and probing pocket depth (PPD). Literature searches were performed across PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) to identify randomized controlled trials and observational clinical studies. After peri-implantitis treatment, PPD was reduced by 0.1 mm (p = 0.58; IC 95% [-0.24, 0.47]), indicating a non-significant effect of antibiotic administration on PPD. The BoP odds ratio value was 1.15 (p = 0.5; IC 95% [0.75, 1.75]), indicating that the likelihood of bleeding is almost similar between the test and control groups. Secondary outcomes were found, such as reduced clinical attachment level, lower suppuration and recession, less bone loss, and a reduction in total bacterial counts. In the treatment of peri-implantitis, the systemic antibiotic application reduces neither PPD nor BoP. Therefore, the systemic administration of antibiotics, in the case of peri-implantitis, should be rethought in light of the present results, contributing to address the problem of increasing antibiotic resistance.

Efficacy of local antibiotic therapy in the treatment of peri-implantitis: A systematic review and meta-analysis.

OBJECTIVES: The aim of this systematic review and meta-analysis was to state the efficacy of local administration of antibiotics in the treatment of peri-implantitis in terms of peri-implant probing depth (PPD) and bleeding on probing (BoP) reduction. DATA, SOURCES AND STUDY SELECTION: Electronic and manual literature searches were conducted. Screening process was done using the National Library of Medicine (MEDLINE by PubMed), Embase and the Cochrane Oral Health. Included articles were randomized controlled trials and observational studies. Weighted means were calculated. Heterogeneity was determined using Higgins (I2). Due to the encountered heterogeneity between the studies being combined, random-effects models were applied in order to analyze effect sizes. Twelve studies (365 patients and 463 implants) were included in the systematic review. After peri-implantitis treatment with local antibiotics, PPD was reduced 1.40 mm (95% confidence interval: 0.82-1.98). When local antibiotics were applied, a 0.30 mm higher reduction of PPD was obtained than in the control group (95% confidence interval: 0.07-0.53). BoP attained an odds ratio value of 1.82 (95% confidence interval: 1.09-3.04), indicating that the likehood of bleeding is almost two-fold when antibiotics are not locally administrated. Adverse effects were not found after applying local antibiotics. CONCLUSIONS: The local antibiotic administration does reduce, without adverse effects, both peri-implant probing depths and bleeding on probing in patients affected by peri-implantitis, if compared to control groups without local antibiotic application. CLINICAL SIGNIFICANCE: Patients with dental implants frequently suffer from peri-implantitis. Clinical features of peri-implantitis lesions include the presence of bleeding on probing and increased peri-implant probing depths. Both BoP and PPD have become reduced after local administration of antibiotics.

Zn-Containing Membranes for Guided Bone Regeneration in Dentistry.

Barrier membranes are employed in guided bone regeneration (GBR) to facilitate bone in-growth. A bioactive and biomimetic Zn-doped membrane with the ability to participate in bone healing and regeneration is necessary. The aim of the present study is to state the effect of doping the membranes for GBR with zinc compounds in the improvement of bone regeneration. A literature search was conducted using electronic databases, such as PubMed, MEDLINE, DIMDI, Embase, Scopus and Web of Science. A narrative exploratory review was undertaken, focusing on the antibacterial effects, physicochemical and biological properties of Zn-loaded membranes. Bioactivity, bone formation and cytotoxicity were analyzed. Microstructure and mechanical properties of these membranes were also determined. Zn-doped membranes have inhibited in vivo and in vitro bacterial colonization. Zn-alloy and Zn-doped membranes attained good biocompatibility and were found to be non-toxic to cells. The Zn-doped matrices showed feasible mechanical properties, such as flexibility, strength, complex modulus and tan delta. Zn incorporation in polymeric membranes provided the highest regenerative efficiency for bone healing in experimental animals, potentiating osteogenesis, angiogenesis, biological activity and a balanced remodeling. Zn-loaded membranes doped with SiO2 nanoparticles have performed as bioactive modulators provoking an M2 macrophage increase and are a potential biomaterial for promoting bone repair. Zn-doped membranes have promoted pro-healing phenotypes.

Melatonin-doped polymeric nanoparticles reinforce and remineralize radicular dentin: Morpho-histological, chemical and biomechanical studies.

OBJECTIVES: To investigate the effectiveness of novel polymeric nanoparticles (NPs) doped with melatonin (ML) in reducing dentin permeability and facilitating dentin remineralization after endodontic treatment. METHODS: The effect of undoped NPs and ML-doped NPs (ML-NPs) was tested in radicular dentin, at 24 h and 6 m. A control group without NPs was included. ML liberation was measured. Radicular dentin was assessed for fluid filtration. Dentin remineralization was analyzed by scanning electron microscopy, AFM, Young's modulus (Ei), Nano DMA-tan delta, and Raman analysis. RESULTS: ML release ranged from 1.85 mg/mL at 24 h to 0.033 mg/mL at 28 d. Both undoped NPs and ML-NPs treated dentin exhibited the lowest microleakage, but samples treated with ML-NPs exhibited hermetically sealed dentinal tubules and extended mineral deposits onto dentin. ML-NPs promoted higher and durable Ei, and functional remineralization at root dentin, generating differences between the values of tan delta among groups and creating zones of stress concentration. Undoped-NPs produced closure of some tubules and porosities at the expense of a relative mineral amorphization. Chemical remineralization based on mineral and organic assessments was higher in samples treated with ML-NPs. When using undoped NPs, precipitation of minerals occurred; however, radicular dentin was not mechanically reinforced but weakened over time. SIGNIFICANCE: Application of ML-NPs in endodontically treated teeth, previous to the canal filling step, is encouraged due to occlusion of dentinal tubules and the reinforcement of the radicular dentin structure.

Zn-doping of silicate and hydroxyapatite-based cements: Dentin mechanobiology and bioactivity.

The objective was to state zinc contribution in the effectiveness of novel zinc-doped dentin cements to achieve dentin remineralization, throughout a literature or narrative exploratory review. Literature search was conducted using electronic databases, such as PubMed, MEDLINE, DIMDI, Embase, Scopus and Web of Science. Both zinc-doping silicate and hydroxyapatite-based cements provoked an increase of both bioactivity and intrafibrillar mineralization of dentin. Zinc-doped hydroxyapatite-based cements (oxipatite) also induced an increase in values of dentin nano-hardness, Young's modulus and dentin resistance to deformation. From Raman analyses, it was stated higher intensity of phosphate peaks and crystallinity as markers of dentin calcification, in the presence of zinc. Zinc-based salt formations produced low microleakage and permeability values with hermetically sealed tubules at radicular dentin. Dentin treated with oxipatite attained preferred crystal grain orientation with polycrystalline lattices. Thereby, oxipatite mechanically reinforced dentin structure, by remineralization. Dentin treated with oxipatite produced immature crystallites formations, accounting for high hydroxyapatite solubility, instability and enhanced remineralizing activity.

State of the Art on Biomaterials for Soft Tissue Augmentation in the Oral Cavity. Part II: Synthetic Polymers-Based Biomaterials.

Most of the polymers used as biomaterials for scaffolds are naturally occurring, synthetic biodegradable, and synthetic non-biodegradable polymers. Since synthetic polymers can be adapted for obtaining singular desired characteristics by applying various fabrication techniques, their use has increased in the biomedical field, in dentistry in particular. The manufacturing methods of these new structures include many processes, such as electrospinning, 3D printing, or the use of computer-aided design/computer-aided manufacturing (CAD/CAM). Synthetic polymers show several drawbacks that can limit their use in clinical applications, such as the lack of cellular recognition, biodegradability, and biocompatibility. Moreover, concerning biodegradable polymers, the time for matrix resorption is not predictable, and non-resorbable matrices are preferred for soft tissue augmentation in the oral cavity. This review aimed to determine a new biomaterial to offset the present shortcomings in the oral environment. Researchers have recently proposed a novel non-resorbable composite membrane manufactured via electrospinning that has allowed obtaining remarkable in vivo outcomes concerning angiogenesis and immunomodulation throughout the polarization of macrophages. A prototype of the protocol for in vitro and in vivo experimentation with hydrogels is explained in order to encourage innovation into the development of promising biomaterials for soft tissue augmentation in the near future.