CORRIGENDUM TO: "Preterm birth and/or low birth weight are associated with periodontal disease and the increased placental immunohistochemical expression of inflammatory markers".

This correct the article DOI: 10.14670/HH-11-671.

Formulation, Colloidal Characterization, and In Vitro Biological Effect of BMP-2 Loaded PLGA Nanoparticles for Bone Regeneration.

Nanoparticles (NPs) based on the polymer poly (lactide-co-glycolide) acid (PLGA) have been widely studied in developing delivery systems for drugs and therapeutic biomolecules, due to the biocompatible and biodegradable properties of the PLGA. In this work, a synthesis method for bone morphogenetic protein (BMP-2)-loaded PLGA NPs was developed and optimized, in order to carry out and control the release of BMP-2, based on the double-emulsion (water/oil/water, W/O/W) solvent evaporation technique. The polymeric surfactant Pluronic F68 was used in the synthesis procedure, as it is known to have an effect on the reduction of the size of the NPs, the enhancement of their stability, and the protection of the encapsulated biomolecule. Spherical solid polymeric NPs were synthesized, showing a reproducible multimodal size distribution, with diameters between 100 and 500 nm. This size range appears to allow the protein to act on the cell surface and at the cytoplasm level. The effect of carrying BMP-2 co-adsorbed with bovine serum albumin on the NP surface was analyzed. The colloidal properties of these systems (morphology by SEM, hydrodynamic size, electrophoretic mobility, temporal stability, protein encapsulation, and short-term release profile) were studied. The effect of both BMP2-loaded NPs on the proliferation, migration, and osteogenic differentiation of mesenchymal stromal cells from human alveolar bone (ABSC) was also analyzed in vitro.

Dual delivery nanosystem for biomolecules. Formulation, characterization, and in vitro release.

Because of the biocompatible and biodegradable properties of poly (lactic-co-glycolic acid) (PLGA), nanoparticles (NPs) based on this polymer have been widely studied for drug/biomolecule delivery and long-term sustained-release. In this work, two different formulation methods for lysozyme-loaded PLGA NPs have been developed and optimized based on the double-emulsion (water/oil/water, W/O/W) solvent evaporation technique. They differ mainly in the phase in which the surfactant (Pluronic® F68) is added: water (W-F68) and oil (O-F68). The colloidal properties of these systems (morphology by SEM and STEM, hydrodynamic size by DLS and NTA, electrophoretic mobility, temporal stability in different media, protein encapsulation, release, and bioactivity) have been analyzed. The interaction surfactant-protein depending on the formulation procedure has been characterized by surface tension and dilatational rheology. Finally, cellular uptake by human mesenchymal stromal cells and cytotoxicity for both systems have been analyzed. Spherical hard NPs are made by the two methods However, in one case, they are monodisperse with diameters of around 120nm (O-F68), and in the other case, a polydisperse system of NPs with diameters between 100 and 500nm is found (W-F68). Protein encapsulation efficiency, release and bioactivity are maintained better by the W-F68 formulation method. This multimodal system is found to be a promising "dual delivery" system for encapsulating hydrophilic proteins with strong biological activity at the cell-surface and cytoplasmic levels.

Cellular, Vascular, and Histomorphometric Outcomes of Solvent-Dehydrated vs Freeze-Dried Allogeneic Graft for Maxillary Sinus Augmentation: A Randomized Case Series.

PURPOSE: The aim of this study was to compare solvent dehydrated human allograft (SDHA; Puros Allograft) and freeze-dried human allograft (FDHA; MinerOss) in order to determine if the allogeneic bone preservation process influences the amount of remaining particles and newly formed bone in maxillary sinus augmentation. MATERIALS AND METHODS: Subjects requiring maxillary lateral sinus augmentation with ridge height < 5 mm were included in this study. Maxillary sinuses were randomly assigned to be grafted with a 1:1 ratio of cortical and cancellous bone, either SDHA or FDHA. In both groups, the graft material was mixed with autogenous bone graft at a ratio of 1:1. Morphologic and histomorphometric analyses were completed 6 months after the grafting procedure. RESULTS: Thirty-four subjects were included in this study. All subjects showed similar demographic characteristics at baseline. Half of the sinuses were grafted with SDHA; the remaining half were grafted with FDHA. Histomorphometric analysis of bone core biopsy samples showed no statistically significant difference between the SDHA or FDHA allogeneic bone substitutes (P = .365), with a mean value of 39.54% ± 0.05% and 31.96% ± 0.08% of mineralized tissue for SDHA and FDHA, respectively. However, a slightly higher mean value of remaining particles was obtained for the FDHA compared with SDHA (18.91% ± 0.09% vs 8.65% ± 0.06%, respectively), although the difference was not statistically significant. Additionally, FDHA demonstrated statistically significantly higher osteoblast, fibroblast, and inflammatory cell numbers. CONCLUSION: Regardless of the preservation process subtype, allogeneic bone grafting material, in combination with autogenous bone, was demonstrated to be effective for maxillary sinus augmentation bone by means of cellular, vascular, and histomorphometric behavior. Nonetheless, FDHA demonstrated higher cellularity compared to SDHA, suggesting accelerated turnover activity for the latter grafting material.

Preterm birth and/or low birth weight are associated with periodontal disease and the increased placental immunohistochemical expression of inflammatory markers.

UNLABELLED: The objective of this study was to determine whether gynecological and periodontal clinical parameters and the immunohistochemical expression in placental chorionic villi of the markers cyclooxygenase-2 (COX-2), interleukin (IL)-1ß, vascular endothelial growth factor receptor 1 (VEGFR1), podoplanin, and Heat Shock Protein 70 (HSP70) are associated with preterm birth (PB) and/or low birth weight (LBW) neonates. MATERIAL AND METHODS: An observational case-control study was performed in 130 puerperal women: mothers of PB/LBW neonates (cases, n=65) and mothers of full-term normal-weight neonates (controls, n=65). Data were gathered from all participants on socio-demographic, gynecological, and periodontal variables and on placental immunohistochemical COX-2, IL-1ß, VEGFR1, podoplanin, and HSP70 expression. RESULTS: Among the 42 women with mild/moderate periodontitis or gingivitis, the studied periodontal variables were significantly worse and the placental COX-2 (p=0.043), HSP70 (p=0.001), IL-1ß (p=0.001), VEGFR1 (p=0.032), and podoplanin (p=0.058) expressions were significantly higher in the cases than in the controls. In comparison to the mothers without periodontitis, only COX-2 (p=0.026) and VEGFR1 (p=0.005) expressions were significantly increased in those with the disease. Increased COX-2 values were detected in the women with a history of genitourinary infection (p=0.036), premature rupture of membrane (p=0.012), or drug treatment (p=0.050). CONCLUSIONS: The etiology of preterm birth and/or low birth weight is multifactorial and involves consumption habits, social-health factors, and infectious episodes. These adverse pregnancy outcomes were associated with periodontitis and the increased placental expression of IL-1ß, COX-2, VEGFR1, and HSP70.

Abutment height influences the effect of platform switching on peri-implant marginal bone loss.

PURPOSE: The purpose was to radiographically analyze and compare the marginal bone loss (MBL) between implants with different mismatching distance and to study the influence of the prosthetic abutment height on the MBL in association with the related mismatching distances. MATERIAL AND METHODS: This retrospective study included 108 patients in whom 228 implants were placed, 180 with diameter of 4.5 mm and 48 with diameter of 5 mm. All patients received OsseoSpeed™ implants with internal tapered conical connection (Denstply Implants). Different mismatching distances were obtained, given that all implants were loaded with the same uni-abutment type (Lilac; Denstply Implants). Data were gathered on age, gender, bone substratum, smoking habits, previous history of periodontitis, and prosthetic features. MBL was analyzed radiographically at 6 and 18 months post-loading. RESULTS: Mixed linear analysis of mesial and distal MBL values yielded significant effects of abutment, implant diameter, follow-up period, bone substratum, smoking, and abutment × time interaction. MBL was greater at 18 vs. 6 months, for short vs. long abutments, for grafted vs. pristine bone, for a heavier smoking habit, and for implants with a diameter of 5.0 vs. 4.5 mm. CONCLUSION: Greater mismatching does not minimize the MBL; abutment height, smoking habit, and bone substratum may play a role in the MBL over the short- and medium term.

Significance of the Immunohistochemical Expression of Bone Morphogenetic Protein-4 in Bone Maturation after Maxillary Sinus Grafting in Humans.

BACKGROUND: Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-ß (TGFß) protein superfamily and are known to be involved in bone and cartilage formation. Within this family, BMP-4 is one of the most studied members. It has been shown to induce osteogenic differentiation of osteoblasts and osteoprogenitor cells in vitro, but the intimate processes in which this protein promotes and regulates osseous repair still remains unclear. PURPOSE: To assess whether the native cellular immunohistochemical expression of BMP-4 correlates with the maturation of bone samples obtained at 6 months after maxillary sinus augmentation. MATERIALS AND METHODS: Histopathological and histomorphometrical analyses were performed in all the samples, which were obtained from a total of 58 patients. Immunohistochemical expression of BMP-4 was analyzed in 30 core biopsies obtained from maxillary sinuses grafted with a combination of anorganic bovine bone and autogenous cortical bone [1:1] (AB-group), and 18 biopsies from maxillary sinuses grafted solely with a cortico-cancellous particulate allograft (M-group), all of them after a 6-month healing period. Also, 10 biopsies of native pristine bone were obtained and used as control group (C-group). RESULTS: Mild to moderate immunohistochemical expression of native granular BMP-4 was present in 56.8% (31.0% AB-group, 22.4% M-group, and 3.4% C-group) (p = 0.000, chi-square) of the specimens analyzed. BMP-4 expression was primarily located in the cytoplasm of osteoblasts, osteoclasts, and epithelial cells of the schneiderian membrane. Whereas significant differences were observed in the proportion of mineralized tissue and cellularity between sinuses grafted with anorganic bovine bone, allograft, or nongrafted sinuses, there were no statistically significant differences in the cellular expression of BMP-4 among groups. CONCLUSION: Our findings suggest that the native expression of BMP-4 appears to be associated with normal bone homeostasis and reparation in grafted and nongrafted maxillary sites.

Bone Regeneration from PLGA Micro-Nanoparticles.

Poly-lactic-co-glycolic acid (PLGA) is one of the most widely used synthetic polymers for development of delivery systems for drugs and therapeutic biomolecules and as component of tissue engineering applications. Its properties and versatility allow it to be a reference polymer in manufacturing of nano- and microparticles to encapsulate and deliver a wide variety of hydrophobic and hydrophilic molecules. It additionally facilitates and extends its use to encapsulate biomolecules such as proteins or nucleic acids that can be released in a controlled way. This review focuses on the use of nano/microparticles of PLGA as a delivery system of one of the most commonly used growth factors in bone tissue engineering, the bone morphogenetic protein 2 (BMP2). Thus, all the needed requirements to reach a controlled delivery of BMP2 using PLGA particles as a main component have been examined. The problems and solutions for the adequate development of this system with a great potential in cell differentiation and proliferation processes under a bone regenerative point of view are discussed.

Effect of barrier membranes on the outcomes of maxillary sinus floor augmentation: a meta-analysis of histomorphometric outcomes.

PURPOSE: Sinus floor elevation via the lateral window approach represents a reliable technique for augmenting bone volume in the atrophic posterior maxilla. However, controversy remains regarding the effect of placement of a barrier membrane over the lateral window. This histomorphometric meta-analysis sought to clarify the effect of barrier membranes in lateral window sinus augmentation. MATERIALS AND METHODS: An electronic search of three databases and a hand search in implant-related journals for studies published through January 2013 in the English language was conducted. Randomized controlled trials, prospective human clinical studies, retrospective investigations, and case series reporting histomorphometric results after sinus elevation using the lateral window approach with at least six patients and a minimum follow-up period of 6 months were included. RESULTS: The initial search yielded 1,040 articles, of which 94 were further evaluated for eligibility. Finally, 37 studies were chosen and separated into membrane (group 1) and no-membrane (group 2) groups. Similar vital bone formation was found in both groups: 32.36% for group 1 and 33.07% for group 2. CONCLUSION: Based does not influence the amount of vital bone formation after sinus augmentation. Additionally, the type of grafting material used and healing time did not influence the histomorphometric outcome.

Marginal bone loss as success criterion in implant dentistry: beyond 2 mm.

AIM: The aim of this study was to analyze marginal bone loss (MBL) rates around implants to establish the difference between physiological bone loss and bone loss due to peri-implantitis. MATERIALS AND METHODS: Five hundred and eight implants were placed in the posterior maxilla in 208 patients. Data were gathered on age, gender, bone substratum (grafted or pristine), prosthetic connection, smoking and alcohol habits, and previous periodontitis. MBL was radiographically analyzed in three time frames (5 months post-surgery and at 6 and 18 months post-loading). Nonparametric receiver operating curve (ROC) analysis and mixed linear model analysis were used to determine whether implants could be classified as high or low bone loser type (BLT) and to establish the influence of this factor on MBL rates. RESULTS: Marginal bone loss rates were significantly affected by BLT, connection type, bone substratum, and smoking. Bone loss rates at 18 months were associated with initial bone loss rates: 96% of implants with an MBL of >2 mm at 18 months had lost 0.44 mm or more at 6 months post-loading. CONCLUSION: Implants with increased MBL rates at early stages (healing and immediate post-loading periods) are likely to reach MBL values that compromise their final outcome. Initial (healing, immediate post-loading) MBL rates around an implant of more than 0.44 mm/year are an indication of peri-implant bone loss progression.

An ex vivo model in human femoral heads for histopathological study and resonance frequency analysis of dental implant primary stability.

OBJECTIVE: This study was designed to explore relationships of resonance frequency analysis (RFA)-assessed implant stability (ISQ values) with bone morphometric parameters and bone quality in an ex vivo model of dental implants placed in human femoral heads and to evaluate the usefulness of this model for dental implant studies. MATERIAL AND METHODS: This ex vivo study included femoral heads from 17 patients undergoing surgery for femoral neck fracture due to osteoporosis (OP) (n = 7) or for total prosthesis joint replacement due to severe hip osteoarthrosis (OA) (n = 10). Sixty 4.5 × 13 mm Dentsply Astra implants were placed, followed by RFA. CD44 immunohistochemical analysis for osteocytes was also carried out. RESULTS: As expected, the analysis yielded significant effects of femoral head type (OA versus OA) (P < 0.001), but not of the implants (P = 0.455) or of the interaction of the two factors (P = 0.848). Bonferroni post hoc comparisons showed a lower mean ISQ for implants in decalcified (50.33 ± 2.92) heads than in fresh (66.93 ± 1.10) or fixated (70.77 ± 1.32) heads (both P < 0.001). The ISQ score (fresh) was significantly higher for those in OA (73.52 ± 1.92) versus OP (67.13 ± 1.09) heads. However, mixed linear analysis showed no significant association between ISQ scores and morphologic or histomorphometric results (P > 0.5 in all cases), and no significant differences in ISQ values were found as a function of the length or area of the cortical layer (both P > 0.08). CONCLUSION: Although RFA-determined ISQ values are not correlated with morphometric parameters, they can discriminate bone quality (OP versus OA). This ex vivo model is useful for dental implant studies.

Sensitivity of resonance frequency analysis for detecting early implant failure: a case-control study.

PURPOSE: The aim of this study was to test the sensitivity of the resonance frequency analysis for detecting early implant failure. MATERIALS AND METHODS: In all, 3,786 implants placed from June 2007 to January 2013 were retrospectively evaluated. A total of 20 implants (in 20 patients) placed in pristine bone were found to have failed before loading. The implant stability quotient (ISQ) values were extracted from these 20 implants at baseline (immediate) and 4 months after placement (delayed). Simple linear regression, logistic regression, and two-way contingency tables were used to test for the relationships between ISQ values and early implant failure. RESULTS: Immediate ISQ values were significantly related to failure (odds ratio [OR] = 4.27). Furthermore, the results of the second regression showed a significant relationship between ISQ at delayed measurement and implant failure (OR = 9.20). For immediate ISQ, it seems that the 73.7% correct classifications were obtained at the cost of an incorrect classification of 55% of the implant failures. However, for the delayed ISQ, 86.2% correct classifications were obtained at the cost of assuming that all implants will survive. CONCLUSION: The present study showed that ISQ values are not reliable in predicting early implant failure. In addition, the real cutoff ISQ value to differentiate between success and early implant failure remains to be determined.

Influence of crown/implant ratio on marginal bone loss: a systematic review.

BACKGROUND: With the increased use of short dental implants (<10 mm), a high crown/implant (C/I) ratio has become a common finding. However, the effect of the C/I ratio on the marginal bone loss (MBL) has not yet been examined extensively. Hence, the aim of the present systematic review is to explore the influence of the C/I ratio on the success rate and MBL of dental implants. METHODS: Three electronic databases (PubMed, Ovid MEDLINE, and Cochrane Central) and a manual search for human trials with a minimal follow-up of 6 months are used for the present study. A statistical analysis of the influence of the C/I ratio was performed on the peri-implant MBL while considering follow-up period, type of implants, implant connection, and technical and biologic complications. RESULTS: One hundred ninety-six potential articles were identified on the selected databases. Only 57 articles were selected for full-text evaluation. According to the inclusion criteria, a total of 13 articles were included in this systematic review. A significant negative association between the C/I ratio and the MBL was found (P = 0.012). However, no statistically significant difference was found (P >0.15) for potential effects regarding the observation period, the type of implant connection, or between both methods of evaluating the C/I ratio. CONCLUSIONS: Within the limitations of the present study, the C/I ratio of implant-supported restorations has an effect on peri-implant marginal bone level. Within the range of 0.6/1 to 2.36/1, the higher the C/I ratio, the less the peri-implant MBL.

The influence of implant diameter on its survival: a meta-analysis based on prospective clinical trials.

BACKGROUND: The use of narrow-diameter implants has been proposed to restore small edentulous spans, thus avoiding extensive bone augmentation procedures and reducing the surgical complexity of implant rehabilitations. Although success rates of narrow-diameter implants have already been analyzed in the literature, to the best of the authors' knowledge, no meta-analysis based on prospective and randomized controlled trials has been performed. The aim of this study is to analyze the survival rates of narrow-diameter implants compared with standard or wide-diameter implants. METHODS: An electronic search from three databases and a hand search in implant-related journals of studies published in English before September 1, 2012 were performed. Prospective human clinical studies with at least 10 implants and a follow-up period of 1 year were included in the meta-analysis. Implants were divided into two groups based on their diameters. RESULTS: The initial search yielded 484 articles, of which 49 were evaluated in full text for eligibility. Finally, 16 studies were chosen and separated into two groups: 1) implants of diameter <3.3 mm (group 1) and 2) implants of diameter ≥3.3 mm (group 2). A meta-analysis performed for groups 1 and 2 showed survival rates of 75% and 87%, respectively. CONCLUSIONS: This meta-analysis showed that narrower implants (<3.3 mm) had significantly lower survival rates compared with wider implants (≥3.3 mm). Other variables, such as type of prosthesis, implant surface, and timing of prosthetic loading, were found to have influenced the implant survival rates.

Effect of rhBMP-2 upon maxillary sinus augmentation: a comprehensive review.

PURPOSE: The purpose of this review was to summarize the recent in vitro and in vivo research findings in areas where rhBMP-2 was used as a grafting material for sinus augmentation. MATERIALS AND METHODS: An electronic literature search for relevant articles published in English was conducted in the PubMed database from February 1996 to August 2012. Randomized clinical trials or prospective human clinical and animal trials were included with the primary objective to compare and evaluate the effectiveness of rhBMP-2 for sinus augmentation. RESULTS: A total of 3 human studies and 4 animal trials qualified the selection criteria that were included in this review. In humans, the selected studies indicated that rhBMP-2 induces new bone formation with comparable bone quality or amount of newly formed bone to that induced by autogenous bone graft. Furthermore, no differences have been reported between new bone induced by rhBMP-2 and native bone. Animal model studies also demonstrated regular bone formation induced by rhBMP-2, followed by normal maturation of new bone. CONCLUSION: All these studies demonstrate the osteoinductive and osteogenic capacity of rhBMP-2 and support it as an alternative for autogenous bone in sinus floor augmentation.