Publications by authors named "Águedo Aragonês"

8 Publications

  • Page 1 of 1

PLGA+HA/βTCP Scaffold Incorporating Simvastatin: A Promising Biomaterial for Bone Tissue Engineering.

J Oral Implantol 2021 Apr;47(2):93-101

Department of Dentistry, Federal University of Santa Catarina, Santa Catarina, Brazil.

The aim of this study was to synthesize, characterize, and evaluate degradation and biocompatibility of poly(lactic-co-glycolic acid) + hydroxyapatite/β-tricalcium phosphate (PLGA+HA/βTCP) scaffolds incorporating simvastatin (SIM) to verify if this biomaterial might be promising for bone tissue engineering. Samples were obtained by the solvent evaporation technique. Biphasic ceramic particles (70% HA, 30% βTCP) were added to PLGA in a ratio of 1:1. Samples with SIM received 1% (m/m) of this medication. Scaffolds were synthesized in a cylindric shape and sterilized by ethylene oxide. For degradation analysis, samples were immersed in phosphate-buffered saline at 37°C under constant stirring for 7, 14, 21, and 28 days. Nondegraded samples were taken as reference. Mass variation, scanning electron microscopy, porosity analysis, Fourier transform infrared spectroscopy, differential scanning calorimetry, and thermogravimetry were performed to evaluate physico-chemical properties. Wettability and cytotoxicity tests were conducted to evaluate the biocompatibility. Microscopic images revealed the presence of macro-, meso-, and micropores in the polymer structure with HA/βTCP particles homogeneously dispersed. Chemical and thermal analyses presented similar results for both PLGA+HA/βTCP and PLGA+HA/βTCP+SIM. The incorporation of simvastatin improved the hydrophilicity of scaffolds. Additionally, PLGA+HA/βTCP and PLGA+HA/βTCP+SIM scaffolds were biocompatible for osteoblasts and mesenchymal stem cells. In summary, PLGA+HA/βTCP scaffolds incorporating simvastatin presented adequate structural, chemical, thermal, and biological properties for bone tissue engineering.
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http://dx.doi.org/10.1563/aaid-joi-D-19-00148DOI Listing
April 2021

In vitro evaluation of bilayer membranes of PLGA/hydroxyapatite/β-tricalcium phosphate for guided bone regeneration.

Mater Sci Eng C Mater Biol Appl 2020 Jul 19;112:110849. Epub 2020 Mar 19.

Mechanical Engineering Department, Federal University of Santa Catarina, Florianópolis, SC 88040-900, Brazil.

Membranes for guided bone regeneration represent valuable resources, preventing fibroblast infiltration and aiding anatomical bone reconstruction. Nonetheless, available membranes lack bone regenerative capacity, suitable mechanical behavior, or adequate degradation profile. Therefore, to overcome these limitations, this study developed bilayer membranes with a dense layer (dry phase inversion) of PLGA (poly(lactic-co-glycolic acid)):HAp (hydroxyapatite) - 95:05 (wt%) - and an electrospun layer of PLGA and HAp:β-TCP (β-tricalcium phosphate) with ratios of 60:40, 70:30 and 85:15 (wt%), evaluating its mechanical, morphological and in vitro properties. The bilayer membranes displayed adequate interlayer adhesion, dense layer pore size of 4.20 μm and electrospun layer with porosity degree of 38.2%, thus capable of preventing fibroblast infiltration while allowing osteoblast migration and nutrient permeation. They also showed T of 82 °C and higher storage modulus, which was constant up to 54.6 °C, characteristics important for membrane implantation and use with no mechanical compromise. In vitro degradation mass loss was only 10% after 60 days, a profile suitable for the application requirement. Membranes with calcium phosphates had better osteoblast attachment, proliferation and migration. Taken together, results indicate the great potential of PLGA/HAp/β-TCP bilayer membranes on bone reconstruction with proper degradation profile, morphology, mechanical behavior and bone regenerative capacity.
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http://dx.doi.org/10.1016/j.msec.2020.110849DOI Listing
July 2020

Titanium coated with poly(lactic-co-glycolic) acid incorporating simvastatin: Biofunctionalization of dental prosthetic abutments.

J Periodontal Res 2020 Jan 7;55(1):116-124. Epub 2019 Sep 7.

Department of Dentistry, Federal University of Santa Catarina, Florianópolis, Brazil.

Objective: To propose a biofunctionalized prosthetic abutment by analyzing physico-chemical and morphological properties, simvastatin (SIM) release, and biocompatibility of titanium (Ti) disks coated with poly(lactic-co-glycolic) acid (PLGA) incorporating SIM.

Methods: Titanium disks (8 × 3 mm) were distributed into four groups: Ti: pure Ti; Ti + PLGA: Ti coated with PLGA; Ti + PLGA + SIM6%: Ti + PLGA with 6% SIM; and Ti + PLGA + SIM0.6%: Ti + PLGA incorporating 0.6% SIM. PLGA was prepared through chloroform evaporation technique. After complete dissolution of PLGA, SIM was diluted in the solution. Ti + PLGA, Ti + PLGA + SIM6%, and Ti + PLGA + SIM0.6% were dip coated with PLGA and PLGA + SIM, respectively. Samples were sterilized by ethylene oxide. For SIM release assay, disks were submerged in PBS, pH 7.4, 37°C, 30 rpm up to 600 hours. At different time intervals, SIM was quantified by spectrophotometry (238 nm). For characterization of the biomaterial components, it was performed Fourier-transform infrared spectroscopy, differential scanning calorimetry, scanning electron microscopy (SEM), optical profilometry, and atomic force microscopy. Biocompatibility analyses were performed by MTS colorimetric assay on murine fibroblasts L929, human gingival fibroblasts (HGFs), and stem cells from human exfoliated deciduous teeth (SHEDs). Absorbance was measured at 490 nm, and percentages of viable cells were calculated in relation to positive control (Ti). SEM images were obtained to verify cell adhesion and morphology. One-way ANOVA followed by Tukey's post hoc test was applied (P < 0.05) for statistical analyses.

Results: SIM release was slow and continuous, reaching about 21% of the incorporated SIM after 600 hours. Topographical analyses revealed success in coating Ti disks with PLGA incorporating SIM. Regarding biocompatibility test, Ti + PLGA + SIM0.6% showed the highest percentage of L929 viability at days 3 and 7. There was no significant difference for Ti, Ti + PLGA, and Ti + PLGA + SIM0.6% groups on cell viability of both SHEDs and HGFs at days 3 and 7. SEM corroborates that SHEDs and HGFs were able to adhere and proliferate on Ti, Ti + PLGA, and Ti + PLGA + SIM0.6% surfaces.

Conclusion: A slow and controlled release of SIM was achieved, attributed to a diffusional mass transfer mechanism. Moreover, a homogenous coating topography was obtained. Additionally, 0.6% SIM incorporated into PLGA coating improved fibroblasts L929 viability compared to titanium or PLGA. Also, 0.6% SIM incorporated into PLGA promoted cell viability of about 100% for HGFs and approximately 150% for human mesenchymal stem cells. Therefore, this study allows to consider the use of PLGA-coated titanium incorporating SIM as a biofunctionalized abutment for dental implants.
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http://dx.doi.org/10.1111/jre.12695DOI Listing
January 2020

Manufacturing and characterization of plates for fracture fixation of bone with biocomposites of poly (lactic acid-co-glycolic acid) (PLGA) with calcium phosphates bioceramics.

Mater Sci Eng C Mater Biol Appl 2019 Oct 8;103:109728. Epub 2019 May 8.

CERMAT, Mechanical Engineering Department, Federal University of Santa Catarina - UFSC, Florianópolis, SC, Brazil.

Commercially, there are several plates and screws for bone fracture fixation made with PLA, however, its long degradation time and lack of integration with bone structure, provides interest in research using polymers with faster degradation, such as PLGA, and together with bioceramics, in order to improve bioactivity in bone regeneration. Based on this, in this study, bone fracture fixation plates composed of PLGA polymer matrix and combinations of 5 and 10%wt. of bioceramics were processed by microinjection. The bioceramics used comprehend nanostructured hydroxyapatite (n-HA), β-tricalcium phosphate (β-TCP) and calcium phosphate with ion substitution of magnesium (Mg-Ca/P) and strontium (Sr-Ca/P). The introduction of bioceramics modified thermal and mechanical properties of the polymer. The TGA analysis showed that there was a variation on the ceramic's mass inserted in relation to the expected values (5% and 10%wt.) in all groups of biocomposites. In general, Tg values obtained by DMA were slightly increased in almost all the biocomposites. The storage modulus (E') of biocomposites was higher for almost all groups of inserted ceramics, with exception of 5%n-HA. In the flexural tests, the biocomposites obtained a great dispersion in average values of fracture loading, presented lower values in relation to pure PLGA. There were difficulties in the processing of biocomposites with Mg-Ca/P and Sr-Ca/P, a factor that can be attributed to lack of homogeneity in the material mixing process. The results suggest modifications in thermal and mechanical properties of the PLGA plates with the bioceramics insertion and provide improvement understanding about of manufactured composites with PLGA and bioceramics.
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http://dx.doi.org/10.1016/j.msec.2019.05.013DOI Listing
October 2019

Release of simvastatin from scaffolds of poly(lactic-co-glycolic) acid and biphasic ceramic designed for bone tissue regeneration.

J Biomed Mater Res B Appl Biomater 2019 08 17;107(6):2152-2164. Epub 2019 Jan 17.

Center for Research on Dental Implants (CEPID), Department of Dentistry, Federal University of Santa Catarina, Florianópolis, Brazil.

The aim of this study was to evaluate the release of simvastatin from scaffolds composed of poly(lactic-co-glycolic) acid (PLGA) and biphasic ceramic designed for bone engineering and to assess the physico-chemical and mechanical properties of the scaffolds. Samples with 30% and 70% porosity were obtained with 0, 2, 5, and 8 wt %. of simvastatin through the solvent evaporation technique and leaching of sucrose particles. Scaffold degradation and simvastatin release were evaluated in phosphate-buffered saline. Scaffolds were analyzed by scanning electron microscopy and microtomography for two-dimensional and three-dimensional morphological characterization of the porosity, connectivity, and intrinsic permeability. The mechanical characterization was conducted based on the compressive strength and the chemical characterization by differential scanning calorimetry and energy dispersive X-ray spectroscopy. Gradual and prolonged simvastatin release from the scaffolds was observed. The release followed the Korsmeyer kinetics model with the predominance of case II transport for 30% porosity scaffolds, and anomalous behavior for the 70% porosity samples. Simvastatin release was also influenced by the slow scaffold degradation due to the strong chemical interaction between simvastatin and PLGA, as observed by differential scanning calorimetry. The scaffolds presented spherical and sucrose crystal-shaped pores that resulted in a homogenous porosity, with a predominance of open pores, ensuring interconnectivity. Simvastatin incorporation into the scaffolds and increased porosity did not influence the mechanical properties. The scaffolds presented gradual and prolonged simvastatin release, with satisfactory physico-chemical and mechanical properties. The scaffolds presented gradual and prolonged simvastatin release, with satisfactory physico-chemical and mechanical properties, a promise for applications in bone regeneration. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2152-2164, 2019.
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http://dx.doi.org/10.1002/jbm.b.34311DOI Listing
August 2019

Ridge Preservation After Maxillary Third Molar Extraction Using 30% Porosity PLGA/HA/β-TCP Scaffolds With and Without Simvastatin: A Pilot Randomized Controlled Clinical Trial.

Implant Dent 2017 Dec;26(6):832-840

Full Professor, Post-graduate Program in Dentistry (PPGO), Center for Research and Education on Dental Implants (CEPID), School of Dentistry (ODT), Federal University of Santa Catarina, UFSC, Florianópolis, Santa Catarina, Brazil.

Objective: To evaluate clinically and radiographically, in humans, the healing of maxillary third molars postextraction sockets after application of different ridge preservation techniques 3 months after tooth extraction.

Materials And Methods: Twenty-six sockets (13 patients) were randomly assigned to 4 treatment modalities: deproteinized bovine bone mineral with 10% collagen (DBBM-C), poly(D,L-lactide-co-glycolide) with hydroxyapatite/β-TCP scaffold (PLGA/HA), PLGA/HA/β-TCP with 2.0% simvastatin scaffold (PLGA/HA/S), and spontaneous healing (control). Clinical complications were assessed, and cone-beam computed tomographies were taken in 5 patients 3 months after surgeries. For statistical purposes, the Fisher exact test was used (P < 0.05).

Results: After 3 months, 6 of 9 grafts from the PLGA/HA group were lost (P < 0.05). PLGA/HA/S' loss was only 2 of 8 (P > 0.05), but no loss was observed in the DBBM-C group. Pain was present in 3 of 8 sites that lost the graft (37.5%) (P > 0.05) and infection in 1 of 8 (12.5%) (P > 0.05), with these only occurring in the PLGA/HA group.

Conclusions: Poly (D, L-lactide-co-glycolide) with hydroxyapatite/β-TCP (PLGA/HA/β-TCP) scaffolds, with and without simvastatin, failed to obtain the initial expected results and presented more complications. Scaffolds with simvastatin showed to be superior, with less clinical complications than scaffolds without simvastatin.
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http://dx.doi.org/10.1097/ID.0000000000000655DOI Listing
December 2017

Study of mesenchymal stem cells cultured on a poly(lactic-co-glycolic acid) scaffold containing simvastatin for bone healing.

J Appl Biomater Funct Mater 2017 Apr 26;15(2):e133-e141. Epub 2017 Apr 26.

Department of Physiological Sciences, Biomaterials Laboratory, Pontifical Catholic University, Sorocaba, São Paulo - Brazil.

Background: Tissue engineering is a promising alternative for the development of bone substitutes; for this purpose, three things are necessary: stem cells, a scaffold to allow tissue growth and factors that induce tissue regeneration.

Methods: To congregate such efforts, we used the bioresorbable and biocompatible polymer poly(lactic-co-glycolic acid) (PLGA) as scaffold. For the osteoinductive factor, we used simvastatin (SIM), a drug with a pleiotropic effect on bone growth. Mesenchymal stem cells (MSCs) were cultured in PLGA containing SIM, and the bone substitute of PLGA/SIM/MSC was grafted into critical defects of rat calvaria.

Results: The in vitro results showed that SIM directly interfered with the proliferation of MSC promoting cell death, while in the pure PLGA scaffold the MSC grew continuously. Scaffolds were implanted in the calvaria of rats and separated into groups: control (empty defect), PLGA pure, PLGA/SIM, PLGA/MSC and PLGA/SIM/MSC. The increase in bone growth was higher in the PLGA/SIM group.

Conclusions: We observed no improvement in the growth of bone tissue after implantation of the PLGA/SIM/MSC scaffold. As compared with in vitro results, our main hypothesis is that the microarchitecture of PLGA associated with low SIM release would have created an in vivo microenvironment of concentrated SIM that might have induced MSC death. However, our findings indicate that once implanted, both PLGA/SIM and PLGA/MSC contributed to bone formation. We suggest that strategies to maintain the viability of MSCs after cultivation in PLGA/SIM will contribute to improvement of bone regeneration.
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http://dx.doi.org/10.5301/jabfm.5000338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379770PMC
April 2017

Adipose-Derived Stem Cells Decrease Bone Morphogenetic Protein Type 2-Induced Inflammation In Vivo.

J Oral Maxillofac Surg 2016 Mar 21;74(3):505-14. Epub 2015 Sep 21.

Professor, Department of Pharmaceutical Sciences, Federal University of Santa Catarina, Florianópolis, Brazil.

Purpose: Recombinant human bone morphogenetic protein type 2 (rhBMP-2) has been used to promote bone regeneration. In contrast, some reports have suggested rhBMP-2 does not provide advantages over autogenous bone grafting owing to the undesirable postoperative symptoms of this growth factor. Because the undesirable symptoms of rhBMP-2 are usually promoted by inflammation, this study evaluated the in vivo effect of human adipose-derived stem cells (ASCs) incorporated into polylactic co-glycolic acid (PLGA) scaffolds in decreasing the inflammatory response induced by a low dose of rhBMP-2.

Materials And Methods: PLGA scaffolds were characterized and loaded with rhBMP-2 1, 2.5, or 5 μg per scaffold (n = 6) and the in vitro released protein amounts were quantified at 7 hours and 1, 7, and 21 days after loading (n = 3). The muscle tissue of 6 beagles received the following treatments: PLGA, PLGA plus rhBMP-2 (2.5 μg), and PLGA plus rhBMP-2 plus ASCs (1 × 10(6) ASCs). The samples were evaluated 45 days after surgery. Statistical analyses were performed and the P value was set at .05.

Results: PLGA plus rhBMP-2 plus ASCs yielded the smallest number of inflammatory foci (P < .001) and giant cells (P < .001) and the largest number of angiogenesis sites (P < .001).

Conclusions: Human ASCs administered in vivo into PLGA scaffolds with a low dose of rhBMP-2 decrease tissue inflammation and increase angiogenesis in muscular sites.
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http://dx.doi.org/10.1016/j.joms.2015.09.006DOI Listing
March 2016