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1.
Acta Biomater ; 2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34496284

RESUMO

Cardiovascular disease is the leading cause of death worldwide, often associated with coronary artery occlusion. A common intervention for arterial blockage utilizes a vascular graft to bypass the diseased artery and restore downstream blood flow; however, current clinical options exhibit high long-term failure rates. Our goal was to develop an off-the-shelf tissue-engineered vascular graft capable of delivering a biological payload based on the monocyte recruitment factor C-C motif chemokine ligand 2 (CCL2) to induce remodeling. Bi-layered silk scaffolds consisting of an inner porous and outer electrospun layer were fabricated using a custom blend of Antherea Assama and Bombyx Mori silk (lyogel). Lyogel silk scaffolds alone (LG), and lyogel silk scaffolds containing microparticles (LGMP) were tested. The microparticles (MPs) were loaded with either CCL2 (LGMP+) or water (LGMP-). Scaffolds were implanted as abdominal aortic interposition grafts in Lewis rats for 1 and 8 weeks. 1-week implants exhibited patency rates of 50% (7/14), 100% (10/10), and 100% (5/5) in the LGMP-, LGMP+, and LG groups, respectively. The significantly higher patency rate for the LGMP+ group compared to the LGMP- group (p = 0.0188) suggests that CCL2 can prevent acute occlusion. Immunostaining of the explants revealed a significantly higher density of macrophages (CD68+ cells) within the outer vs. inner layer of LGMP- and LGMP+ constructs but not in LG constructs. After 8 weeks, there were no significant differences in patency rates between groups. All patent scaffolds at 8 weeks showed signs of remodeling; however, stenosis was observed within the majority of explants. This study demonstrated the successful fabrication of a custom blended silk scaffold functionalized with cell-mimicking microparticles to facilitate controlled delivery of a biological payload improving their in vivo performance. STATEMENT OF SIGNIFICANCE: This study outlines the development of a custom blended silk-based tissue-engineered vascular graft (TEVG) for use in arterial bypass or replacement surgery. A custom mixture of silk was formulated to improve biocompatibility and cellular binding to the tubular scaffold. Many current approaches to TEVGs include cells that encourage graft cellularization and remodeling; however, our technology incorporates a microparticle based delivery platform capable of delivering bioactive molecules that can mimic the function of seeded cells. In this study, we load the TEVGs with microparticles containing a monocyte attractant and demonstrate improved performance in terms of unobstructed blood flow versus blank microparticles. The acellular nature of this technology potentially reduces risk, increases reproducibility, and results in a more cost-effective graft when compared to cell-based options.

2.
Dent Mater ; 37(8): 1316-1324, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34144794

RESUMO

OBJECTIVES: The purpose of the study was to evaluate the integrity of dentine type I collagen after self-etching (SE) treatments with strong and mild universal adhesives. METHODS: Coronal dentine specimens (n=10/product) were imaged by optical microscopy and analyzed by ATR-FTIR spectroscopy before and after treatment with 32% phosphoric acid gel (PA-negative control), 17% neutral EDTA (ED-positive control) conditioners and Adhese Universal (AD), Clearfil Universal Bond Quick (CQ), G-Premio Bond (GP), Prelude One (PR) and Scotchbond Universal (SB) adhesives. From the spectroscopic analysis the following parameters were determined: a) Extent of dentine demineralization (DM%) and b) percentage area of the Amide I curve-fitted components of ß-turns, 310-helix/ß-turns, α-helix, random coils, ß-sheets and collagen maturation (R) index. Statistical analysis was performed by one-way ANOVA (DM%), paired t-test/Wilcoxon test (Amide I components) and Spearman correlation coefficient (DM% vs Amide I components) at an a=0.05 level. RESULTS: PA, ED and GP removed the smear-layer and opened tubule orifices, whereas all other treatments removed only the intratubular smear-layer fraction. The ranking of the statistically significant differences in DM% was PA>GP>ED>AD, SB, CQ, PR, with AD being significantly different from PR. Regarding the Amide I components, PA demonstrated a significant reduction in ß-turns, α-helices and an increase in ß-sheets, GP a reduction in ß-turns, AD an increase in ß-turns and random coils, and CQ an increase in ß-turns. PR, SB and ED showed insignificant differences in all the Amide I components. Significant correlations were found between DM%-random coils and DM%-R. SIGNIFICANCE: The universal adhesives used in the SE mode induced none to minimal changes in dentine collagen structure, without evidence of the destabilization pattern observed after conventional phosphoric acid treatments.


Assuntos
Colagem Dentária , Adesivos Dentinários , Condicionamento Ácido do Dente , Colágeno , Cimentos Dentários , Dentina , Teste de Materiais , Cimentos de Resina , Propriedades de Superfície , Resistência à Tração
3.
J Immunol ; 206(10): 2386-2392, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33952619

RESUMO

Periodontal disease (PD) is a chronic destructive inflammatory disease of the tooth-supporting structures that leads to tooth loss at its advanced stages. Although the disease is initiated by a complex organization of oral microorganisms in the form of a plaque biofilm, it is the uncontrolled immune response to periodontal pathogens that fuels periodontal tissue destruction. IL-17A has been identified as a key cytokine in the pathogenesis of PD. Despite its well documented role in host defense against invading pathogens at oral barrier sites, IL-17A-mediated signaling can also lead to a detrimental inflammatory response, causing periodontal bone destruction. In this study, we developed a local sustained delivery system that restrains IL-17A hyperactivity in periodontal tissues by incorporating neutralizing anti-IL-17A Abs in poly(lactic-coglycolic) acid microparticles (MP). This formulation allowed for controlled release of anti-IL-17A in the periodontium of mice with ligature-induced PD. Local delivery of anti-IL-17A MP after murine PD induction inhibited alveolar bone loss and osteoclastic activity. The anti-IL-17A MP formulation also decreased expression of IL-6, an IL-17A target gene known to induce bone resorption in periodontal tissues. This study demonstrates proof of concept that local and sustained release of IL-17A Abs constitutes a promising therapeutic strategy for PD and may be applicable to other osteolytic bone diseases mediated by IL-17A-driven inflammation.


Assuntos
Perda do Osso Alveolar/tratamento farmacológico , Perda do Osso Alveolar/imunologia , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Neutralizantes/imunologia , Sistemas de Liberação de Medicamentos/métodos , Interleucina-17/imunologia , Periodontite/tratamento farmacológico , Periodontite/imunologia , Animais , Cápsulas , Modelos Animais de Doenças , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Osteólise/tratamento farmacológico , Osteólise/imunologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Resultado do Tratamento
4.
Artigo em Inglês | MEDLINE | ID: mdl-32086204

RESUMO

Acute coronary syndromes and strokes are mainly caused by atherosclerotic plaque (AP) rupture. Abnormal increase of vasa vasorum (VV) is reported as a key evidence of plaque progression and vulnerability. However, due to their tiny size, it is still challenging to noninvasively identify VV near the major vessels. Ultrasound super resolution (USR), a technique that provides high spatial resolution beyond the acoustic diffraction limit, demonstrated an adequate spatial resolution for VV detection in early studies. However, a thorough validation of this technology in the plaque model is particularly needed in order to continue further extended preclinical studies. In this letter, we present an experiment protocol that verifies the USR technology for VV identification with subsequent histology and ex vivo micro-computed tomography ( µ CT). Deconvolution-based USR imaging was applied on two rabbits to identify the VV near the AP in the femoral artery. Histology and ex vivo µ CT imaging were performed on excised femoral tissue to validate the USR technique both pathologically and morphologically. This established validation protocol could facilitate future extended preclinical studies toward the clinical translation of USR imaging for VV identification.


Assuntos
Processamento de Imagem Assistida por Computador/métodos , Placa Aterosclerótica/diagnóstico por imagem , Ultrassonografia/métodos , Vasa Vasorum/diagnóstico por imagem , Algoritmos , Animais , Masculino , Coelhos , Reprodutibilidade dos Testes
5.
Acta Biomater ; 98: 142-151, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31330328

RESUMO

Magnesium (Mg) alloys are embraced for their biodegradability and biocompatibility. However, Mg degrades spontaneously in the biological environment in vivo and in vitro, triggering deposition of calcium phosphate on the metal. Upon complete metal absorption, minerals remain in the tissue, which could lead to pathogenic calcification. Hence, our aims are to test the feasibility of matrix GLA protein (MGP) to locally inhibit Mg mineralization that is induced by metal alloy degradation. MGP is a small secretory protein that has been shown to inhibit soft tissue calcification. We exposed Mg to MGP, stably transfected into mammalian cells. Results showed that less calcium and phosphorous deposition on the Mg surface when MGP was present relative to when it was not. In the in vivo mouse intramuscular model conducted for 4 and 6 weeks, Mg rods were embedded in collagen scaffolds, seeded with cells overexpressing MGP. Microtomography, electron dispersive x-ray spectroscopy, and histology assessments revealed lower deposited mineral volume around Mg rods from the MGP group. Compared to other groups, higher volume loss after implantation was observed from the MGP group at both time points, indicating a higher corrosion rate without the protective mineral layer. This study is the first to our knowledge to demonstrate that local exposure to a biomolecule, such as MGP, can modulate the corrosion of Mg-based implants. These findings may have important implications for the future design of endovascular stents and orthopedic devices.


Assuntos
Proteínas de Ligação ao Cálcio/química , Proteínas da Matriz Extracelular/química , Magnésio/química , Minerais/química , Animais , Colágeno/química , Corrosão , Proteínas de Fluorescência Verde/metabolismo , Células HEK293 , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Implantes Experimentais , Masculino , Metais/química , Camundongos Endogâmicos BALB C , Camundongos Nus , Ratos , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície , Tecidos Suporte/química , Microtomografia por Raio-X
6.
Acta Biomater ; 98: 246-255, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31181262

RESUMO

Magnesium (Mg)-based implants have become of interest to both academia and the medical industry. The attraction largely is due to Mg's biodegradability and ability to enhance bone healing and formation. However, the underlying mechanism of how Mg regulates osteogenesis is still unclear. Based on our previous in vivo and molecular signaling work demonstrating the osteogenic effect of Mg, the current study aims to extend this work at the molecular level especially that we also observed and quantified mineral deposits in the bone marrow space in a rabbit ulna fracture model with Mg plates and screws. Histological analysis and quantitative results of micro-CT showed mineralized deposition and a significant increase in bone volume at 8 weeks and 16 weeks post-operative. These in vivo results led us to focus on studying the effect of Mg2+ on human bone marrow stromal cells (hBMSCs). The data presented in this manuscript demonstrate the activation of the canonical Wnt signaling pathway in hBMSCs when treated with 10 mM Mg2+. With additional Mg2+ present, the protein expression of active ß-catenin was significantly increased to a level similar to that of the positive control. Immunocytochemistry and the increased expression of LEF1 and Dkk1, downstream target genes that are controlled directly by active ß-catenin, demonstrated the protein translocation and the activation of transcription. Taken together, these data suggest that Mg2+ induces an osteogenic effect in the bone marrow space by activating the canonical Wnt signaling pathway, which in turn causes BMSCs to differentiate toward the osteoblast lineage. STATEMENT OF SIGNIFICANCE: Magnesium (Mg)-based alloys are being studied to be used in the field of implantable medical devices due to its natural biodegradability and the potential ability to promote bone regeneration. Despite many in vivo studies that demonstrated an increased new bone growth by implanting Mg-based devices, the underlying mechanism of this effect is still unclear. In order to safely use Mg-based implants on human and better control the osteogenic effect, it is necessary to understand the corresponding cellular response in the targeted area. The present study provides the rationale to study Mg ions on bone marrow stromal cells and shows the activation of canonical Wnt signaling pathway that promotes osteogenesis by in vivo and in vitro approaches.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Magnésio/farmacologia , Via de Sinalização Wnt/efeitos dos fármacos , Fosfatase Alcalina/metabolismo , Animais , Calcificação Fisiológica/efeitos dos fármacos , Íons , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Coelhos , Transcrição Genética/efeitos dos fármacos , Via de Sinalização Wnt/genética , Microtomografia por Raio-X , beta Catenina/metabolismo
7.
J Endod ; 42(12): 1779-1783, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27871481

RESUMO

INTRODUCTION: Recently, we reported that in mandibular molars contracted endodontic cavities (CECs) improved fracture strength compared with traditional endodontic cavities (TECs) but compromised instrumentation efficacy in distal canals. This study assessed the impacts of CECs on instrumentation efficacy and axial strain responses in maxillary molars. METHODS: Eighteen extracted intact maxillary molars were imaged with micro-computed tomographic imaging (12-µm voxel), assigned to CEC or TEC groups (n = 9/group), and accessed accordingly. Canals were instrumented (V-Taper2H; SSWhite Dental, Lakewood, NJ) with 2.5% sodium hypochlorite irrigation, reimaged, and the proportion of the modified canal wall determined. Cavities were restored with bonded composite resin (TPH-Spectra-LV; Dentsply International, York, PA). Another 28 similar molars (n = 14/group) with linear strain gauges (Showa Measuring Instruments, Tokyo, Japan) attached to mesiobuccal and palatal roots were subjected to load cycles (50-150 N) in the Instron Universal Testing machine (Instron, Canton, MA), and the axial microstrain was recorded before access and after restoration. These 28 molars and additional 11 intact molars (control) were cyclically fatigued (1 million cycles, 5-50 N, 15 Hz) and subsequently loaded to failure. Data were analyzed by the Wilcoxon rank sum and Kruskal-Wallis tests (α = 0.05). RESULTS: The overall mean proportion of the modified canal wall did not differ significantly between CECs (49.7% ± 12.0%) and TECs (44.7% ± 9.0%). Relative changes in axial microstrain responses to load varied in both groups. The mean load at failure for CECs (1703 ± 558 N) did not differ significantly from TECs (1384 ± 377 N) and was significantly lower (P < .005) for both groups compared with intact molars (2457 ± 941 N). CONCLUSIONS: In maxillary molars tested in vitro, CECs did not impact instrumentation efficacy and biomechanical responses compared with TECs.


Assuntos
Preparo da Cavidade Dentária/métodos , Cavidade Pulpar , Dente Molar/anatomia & histologia , Preparo de Canal Radicular/métodos , Estresse Mecânico , Fraturas dos Dentes/etiologia , Fenômenos Biomecânicos , Resinas Compostas , Preparo da Cavidade Dentária/instrumentação , Restauração Dentária Permanente/métodos , Análise do Estresse Dentário , Humanos , Teste de Materiais , Maxila , Irrigantes do Canal Radicular/uso terapêutico , Preparo de Canal Radicular/efeitos adversos , Preparo de Canal Radicular/instrumentação , Hipoclorito de Sódio/uso terapêutico , Ápice Dentário/anatomia & histologia , Coroa do Dente/anatomia & histologia , Raiz Dentária/lesões , Microtomografia por Raio-X/métodos
8.
Acta Biomater ; 10(5): 2323-32, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24384125

RESUMO

Recently, magnesium (Mg) alloys have received significant attention as potential biomaterials for degradable implants, and this study was directed at evaluating the suitability of Mg for craniofacial bone screws. The objective was to implant screws fabricated from commercially available pure Mg and alloy AZ31 in vivo in a rabbit mandible. First, Mg and AZ31 screws were compared to stainless steel screws in an in vitro pull-out test and determined to have a similar holding strength (∼40N). A finite-element model of the screw was created using the pull-out test data, and this model can be used for future Mg alloy screw design. Then, Mg and AZ31 screws were implanted for 4, 8 and 12weeks, with two controls of an osteotomy site (hole) with no implant and a stainless steel screw implanted for 12weeks. Microcomputed tomography was used to assess bone remodeling and Mg/AZ31 degradation, both visually and qualitatively through volume fraction measurements for all time points. Histological analysis was also completed for the Mg and AZ31 at 12weeks. The results showed that craniofacial bone remodeling occurred around both Mg and AZ31 screws. Pure Mg had a different degradation profile than AZ31; however, bone growth occurred around both screw types. The degradation rate of both Mg and AZ31 screws in the bone marrow space and the muscle were faster than in the cortical bone space at 12weeks. Furthermore, it was shown that by alloying Mg, the degradation profile could be changed. These results indicate the promise of using Mg alloys for craniofacial applications.


Assuntos
Implantes Absorvíveis , Ligas/farmacologia , Materiais Biocompatíveis/farmacologia , Parafusos Ósseos , Magnésio/farmacologia , Crânio/efeitos dos fármacos , Animais , Simulação por Computador , Face , Feminino , Análise de Elementos Finitos , Processamento de Imagem Assistida por Computador , Teste de Materiais , Coelhos , Crânio/diagnóstico por imagem , Microtomografia por Raio-X
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