Colloidal systems in bone regeneration. Is the size important

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. Its properties and versatility make it a reference polymer in the manufacturing of nano and microparticles to encapsulate and deliver a wide variety of hydrophobic and hydrophilic molecules, including biomolecules such as proteins or nucleic acids that must be released in a controlled way [1]. Delivery of growth factors such as bone morphogenetic proteins, and specially BMP-2, is an attractive therapeutic strategy for bone tissue engineering. However, their administration is problematic due to their short biological half-lives, localized action and rapid clearance. Consequently, its clinical use requires high doses far exceeding its physiological concentration which implies possible side effects and high costs. These barriers might be overcome by developing new delivery systems which allow a better control of the release rate in order to achieve the desired concentrations in specific site and time [2]. With this aim, in this preliminary study we have synthesized PLGA particles with different diameters, from nano (200 nm) to micro scale (12.5 μm) via double emulsion procedure, in order to study the influence of size in the release profile of lysozyme, which has been selected as an appropriate model for BMP2. A physico-chemical characterization of the particles was done, followed by a complete study on the encapsulation efficiency, cumulative protein release and bioactivity of the released enzyme with and without co-encapsulated bovine serum albumin, a protective biomolecule that can prevent protein instability during emulsification process. Additionally, fluorescently labeled lysozyme was used to study the protein distribution and the influence of particle size on the in vitro cellular uptake.Universidad de Málaga. Campus Internacional de Andalucía Tec

Influence of Crown/Implant Ratio on Marginal Bone Loss: A Systematic Review

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141451/1/jper1214.pd

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.The authors wish to express their appreciation for the financial support granted by the “Ministerio de Educación y Ciencia” (MEC, Spain), Projects MAT2013-43922-R, and Research Groups no. FQM-115, no. CTS-138, and no. CTS-583 (Junta de Andalucía, Spain). Partial support was also provided by the Andalucía Talent Hub Program from the Andalusian Knowledge Agency, cofunded by the European Union’s Seventh Framework Program, Marie Skłodowska-Curie actions (COFUND, Grant Agreement no. 291780) and the Ministry of Economy, Innovation, Science and Employment of the Junta de Andalucía (Miguel Padial-Molina)

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

The following are available online at https://www.mdpi.com/1999-4923/11/8/388/s1, Figure S1. Scheme of the formulation of NP-BMP2; Figure S2: Scheme of the protein adsorption process for NP-BSA-BMP2; Video S1. NTA experiments for NP-BMP2; Video S2. NTA experiments for empty NPs.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.This research was funded by the Consejería de Economía, Innovación, Ciencia y Empleo de la Junta de Andalucía (Spain) through research groups FQM-115 and CTS-1028, by the following research project: MAT2013-43922-R—European FEDER support included—(MICINN, Spain) and by MIS Ibérica S.L

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) ( ) or for total prosthesis joint replacement due to severe hip osteoarthrosis (OA) ( ). Sixty  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) ( ), but not of the implants ( ) or of the interaction of the two factors ( ). Bonferroni post hoc comparisons showed a lower mean ISQ for implants in decalcified ( ) heads than in fresh ( ) or fixated ( ) heads (both ). The ISQ score (fresh) was significantly higher for those in OA ( ) versus OP ( ) heads. However, mixed linear analysis showed no significant association between ISQ scores and morphologic or histomorphometric results ( 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 ). 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.This investigation was partially supported by Research Group no. CTS-138 (Junta de Andalucía, Spain)

Bio-nanotecnología aplicada a la regeneración ósea mediante el transporte de biomoléculas usando nanopartículas poliméricas: estudio in vitro

Beca de investigación obtenida competitivamente y otorgada por la empresa de implantes dentales “MIS IBERICA SL” Financiación parcial otorgada 1.- por la Consejería de Economía, Innovación, Educación, Ciencia y Empleo de la Junta de Andalucía (España), 2.- los proyectos MAT2013-43922-R – incluyendo soporte europeo FEDER - (MICINN, España), 3.- y los Grupos de Investigación # FQM-115, # CTS-1028 # CTS-138 y # CTS- 583 (Junta de Andalucía, España).Este trabajo se centra en el uso de nanopartículas (NP) de PLGA como un sistema de entrega de uno de los factores de crecimiento más comúnmente utilizados en la ingeniería del tejido óseo, la proteína morfogenética ósea 2 (BMP2). Por lo tanto, examinamos todos los requisitos necesarios para alcanzar una correcta encapsulación y una liberación controlada y sostenida de BMP2 utilizando partículas de PLGA como componente principal, discutiendo todos los problemas y soluciones que hemos encontrado para el desarrollo adecuado de este sistema con un gran potencial en el proceso de diferenciación celular y proliferación bajo el punto de vista de la regeneración ósea.This work focuses on the use of PLGA nanoparticles (NP) as a delivery system for one of the most commonly used growth factors in bone tissue engineering, bone morphogenetic protein 2 (BMP2). Therefore, we examine all the necessary requirements to achieve a correct encapsulation and a controlled and sustained release of BMP2 using PLGA particles as the main component, discussing all the problems and solutions that we have found for the proper development of this system with great potential. in the process of cell differentiation and proliferation from the point of view of bone regeneration.Tesis Univ. Granada.MIS IBERICA SLConsejería de Economía, Innovación, Educación, Ciencia y Empleo de la Junta de Andalucía (España)MAT2013-43922-R – incluyendo soporte europeo FEDER - (MICINN, España)Grupos de Investigación # FQM-115, # CTS-1028 # CTS-138 y # CTS- 583 (Junta de Andalucía, España)

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

AimThe 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 methodsFive 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.ResultsMarginal 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.ConclusionImplants 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.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110829/1/clr12324.pd

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

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 cyclooxygenase2 (COX-2), interleukin (IL)-1β, vascular endothelial growth factor receptor 1 (VEGFR1), podoplanin, and Heat Shock Protein (HSP70) are associated with preterm birth (PB) and/or low birth weight (LBW) neonates. Material and methods: An observational casecontrol 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 sociodemographic, gynecological, and periodontal variables and on placental immunohistochemical COX-2, IL-1β, 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-1β (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-1β, COX-2, VEGFR1, and HSP70

The Influence of Implant Diameter on Its Survival: A Metaâ Analysis Based on Prospective Clinical Trials

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141793/1/jper0569.pd