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1.
Int J Mol Sci ; 22(14)2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34298988

RESUMO

This study evaluated the biocompatibility and biological performance of novel additive-manufactured bioabsorbable iron-based porous suture anchors (iron_SAs). Two types of bioabsorbable iron_SAs, with double- and triple-helical structures (iron_SA_2_helix and iron_SA_3_helix, respectively), were compared with the synthetic polymer-based bioabsorbable suture anchor (polymer_SAs). An in vitro mechanical test, MTT assay, and scanning electron microscope (SEM) analysis were performed. An in vivo animal study was also performed. The three types of suture anchors were randomly implanted in the outer cortex of the lateral femoral condyle. The ultimate in vitro pullout strength of the iron_SA_3_helix group was significantly higher than the iron_SA_2_helix and polymer_SA groups. The MTT assay findings demonstrated no significant cytotoxicity, and the SEM analysis showed cells attachment on implant surface. The ultimate failure load of the iron_SA_3_helix group was significantly higher than that of the polymer_SA group. The micro-CT analysis indicated the iron_SA_3_helix group showed a higher bone volume fraction (BV/TV) after surgery. Moreover, both iron SAs underwent degradation with time. Iron_SAs with triple-helical threads and a porous structure demonstrated better mechanical strength and high biocompatibility after short-term implantation. The combined advantages of the mechanical superiority of the iron metal and the possibility of absorption after implantation make the iron_SA a suitable candidate for further development.


Assuntos
Implantes Absorvíveis , Materiais Biocompatíveis , Âncoras de Sutura , Alanina Transaminase/sangue , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/toxicidade , Fenômenos Biomecânicos , Nitrogênio da Ureia Sanguínea , Fosfatos de Cálcio/química , Fosfatos de Cálcio/toxicidade , Sulfato de Cálcio/administração & dosagem , Sulfato de Cálcio/química , Sulfato de Cálcio/toxicidade , Creatinina/sangue , Desenho de Equipamento , Fêmur/diagnóstico por imagem , Fêmur/ultraestrutura , Ferro , Lasers , Teste de Materiais , Microscopia Eletrônica de Varredura , Estrutura Molecular , Osseointegração , Polímeros/química , Polímeros/toxicidade , Porosidade , Coelhos , Distribuição Aleatória , Resistência à Tração , Vísceras , Microtomografia por Raio-X
2.
Sci Rep ; 11(1): 9610, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33953260

RESUMO

We demonstrated the design of pre-additive manufacturing microalloying elements in tuning the microstructure of iron (Fe)-based alloys for their tunable mechanical properties. We tailored the microalloying stoichiometry of the feedstock to control the grain sizes of the metallic alloy systems. Two specific microalloying stoichiometries were reported, namely biodegradable iron powder with 99.5% purity (BDFe) and that with 98.5% (BDFe-Mo). Compared with the BDFe, the BDFe-Mo powder was found to have lower coefficient of thermal expansion (CTE) value and better oxidation resistance during consecutive heating and cooling cycles. The selective laser melting (SLM)-built BDFe-Mo exhibited high ultimate tensile strength (UTS) of 1200 MPa and fair elongation of 13.5%, while the SLM-built BDFe alloy revealed a much lower UTS of 495 MPa and a relatively better elongation of 17.5%, indicating the strength enhancement compared with the other biodegradable systems. Such an enhanced mechanical behavior in the BDFe-Mo was assigned to the dominant mechanism of ferrite grain refinement coupled with precipitate strengthening. Our findings suggest the tunability of outstanding strength-ductility combination by tailoring the pre-additive manufacturing microalloying elements with their proper concentrations.

3.
BMC Musculoskelet Disord ; 22(1): 171, 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33573634

RESUMO

BACKGROUND: We developed a porous Ti alloy/PEEK composite interbody cage by utilizing the advantages of polyetheretherketone (PEEK) and titanium alloy (Ti alloy) in combination with additive manufacturing technology. METHODS: Porous Ti alloy/PEEK composite cages were manufactured using various controlled porosities. Anterior intervertebral lumbar fusion and posterior augmentation were performed at three vertebral levels on 20 female pigs. Each level was randomly implanted with one of the five cages that were tested: a commercialized pure PEEK cage, a Ti alloy/PEEK composite cage with nonporous Ti alloy endplates, and three composite cages with porosities of 40, 60, and 80%, respectively. Micro-computed tomography (CT), backscattered-electron SEM (BSE-SEM), and histological analyses were performed. RESULTS: Micro-CT and histological analyses revealed improved bone growth in high-porosity groups. Micro-CT and BSE-SEM demonstrated that structures with high porosities, especially 60 and 80%, facilitated more bone formation inside the implant but not outside the implant. Histological analysis also showed that bone formation was higher in Ti alloy groups than in the PEEK group. CONCLUSION: The composite cage presents the biological advantages of Ti alloy porous endplates and the mechanical and radiographic advantages of the PEEK central core, which makes it suitable for use as a single implant for intervertebral fusion.


Assuntos
Fusão Vertebral , Titânio , Animais , Desenvolvimento Ósseo , Feminino , Cetonas , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Polietilenoglicóis , Porosidade , Suínos , Microtomografia por Raio-X
4.
Brain ; 143(11): 3352-3373, 2020 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-33141179

RESUMO

Parkinson's disease is a neurodegenerative disorder with a multifactorial aetiology. Nevertheless, the genetic predisposition in many families with multi-incidence disease remains unknown. This study aimed to identify novel genes that cause familial Parkinson's disease. Whole exome sequencing was performed in three affected members of the index family with a late-onset autosomal-dominant parkinsonism and polyneuropathy. We identified a novel heterozygous substitution c.941A>C (p.Tyr314Ser) in the mitochondrial ubiquinol-cytochrome c reductase core protein 1 (UQCRC1) gene, which co-segregates with disease within the family. Additional analysis of 699 unrelated Parkinson's disease probands with autosomal-dominant Parkinson's disease and 1934 patients with sporadic Parkinson's disease revealed another two variants in UQCRC1 in the probands with familial Parkinson's disease, c.931A>C (p.Ile311Leu) and an allele with concomitant splicing mutation (c.70-1G>A) and a frameshift insertion (c.73_74insG, p.Ala25Glyfs*27). All substitutions were absent in 1077 controls and the Taiwan Biobank exome database from healthy participants (n = 1517 exomes). We then assayed the pathogenicity of the identified rare variants using CRISPR/Cas9-based knock-in human dopaminergic SH-SY5Y cell lines, Drosophila and mouse models. Mutant UQCRC1 expression leads to neurite degeneration and mitochondrial respiratory chain dysfunction in SH-SY5Y cells. UQCRC1 p.Tyr314Ser knock-in Drosophila and mouse models exhibit age-dependent locomotor defects, dopaminergic neuronal loss, peripheral neuropathy, impaired respiratory chain complex III activity and aberrant mitochondrial ultrastructures in nigral neurons. Furthermore, intraperitoneal injection of levodopa could significantly improve the motor dysfunction in UQCRC1 p.Tyr314Ser mutant knock-in mice. Taken together, our in vitro and in vivo studies support the functional pathogenicity of rare UQCRC1 variants in familial parkinsonism. Our findings expand an additional link of mitochondrial complex III dysfunction in Parkinson's disease.


Assuntos
Mitocôndrias/genética , Transtornos Parkinsonianos/genética , Polineuropatias/genética , Idade de Início , Idoso , Animais , Antiparkinsonianos/uso terapêutico , Linhagem Celular , Aberrações Cromossômicas , Drosophila , Complexo III da Cadeia de Transporte de Elétrons/genética , Feminino , Mutação da Fase de Leitura , Técnicas de Introdução de Genes , Genes Dominantes , Humanos , Levodopa/uso terapêutico , Masculino , Camundongos , Pessoa de Meia-Idade , Mutação/genética , Transtornos Parkinsonianos/complicações , Transtornos Parkinsonianos/tratamento farmacológico , Linhagem , Polineuropatias/etiologia , Sequenciamento Completo do Exoma
5.
Int J Mol Sci ; 21(20)2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33050160

RESUMO

In this study, we optimized the geometry and composition of additive-manufactured pedicle screws. Metal powders of titanium-aluminum-vanadium (Ti-6Al-4V) were mixed with reactive glass-ceramic biomaterials of bioactive glass (BG) powders. To optimize the geometry of pedicle screws, we applied a novel numerical approach to proposing the optimal shape of the healing chamber to promote biological healing. We examined the geometry and composition effects of pedicle screw implants on the interfacial autologous bone attachment and bone graft incorporation through in vivo studies. The addition of an optimal amount of BG to Ti-6Al-4V leads to a lower elastic modulus of the ceramic-metal composite material, effectively reducing the stress-shielding effects. Pedicle screw implants with optimal shape design and made of the composite material of Ti-6Al-4V doped with BG fabricated through additive manufacturing exhibit greater osseointegration and a more rapid bone volume fraction during the fracture healing process 120 days after implantation, per in vivo studies.


Assuntos
Alumínio , Desenvolvimento Ósseo , Vidro , Parafusos Pediculares , Pós , Próteses e Implantes , Titânio , Vanádio , Animais , Fenômenos Biomecânicos , Remodelação Óssea , Processamento de Imagem Assistida por Computador , Osseointegração , Estresse Mecânico , Suínos , Tomografia Computadorizada por Raios X
6.
Dent Mater ; 36(11): 1437-1451, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32962852

RESUMO

OBJECTIVE: Our aim is to examine the mechanical properties of two types of additive manufactured hollow porous dental implants and 6 and 12-week bone ingrowth after insertion in animals. A 3D numerical model is also developed to show detailed tissue differentiation and to provide design guidelines for implants. METHODS: The two porous and a commercial dental implant were studied by series of in vitro mechanical tests (three-point bending, torsional, screwing torque, and sawbone pull-out tests). They also evaluated by in vivo animal tests (micro-CT analysis) and ex vivo pull-out tests. Moreover, the mechano-regulation algorithm was implemented by the 3D finite element model to predict the history of tissue differentiation around the implants. RESULTS: The results showed that the two porous implants can significantly improve osseointegration after 12-week bone healing. This resulted in good fixation and stability of implants, giving very high maximum pull-out strength 413.1 N and 493.2 N, compared to 245.7 N for the commercial implant. Also, several features were accurately predicted by the mechano-regulation model, such as transversely connected bone formation, and bone resorption occurred in the middle of implants. SIGNIFICANCE: Systematic studies on dental implants with multiple approaches, including new design, mechanical tests, animal tests, and numerical modeling, were performed. Two hollow porous implants significantly improved bone ingrowth compared with commercial implants, while maintaining mechanical strength. Also, the numerical model was verified by animal tests. It improved the efficiency of design and reduce the demand for animal sacrifice.

7.
Int J Mol Sci ; 21(10)2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32455543

RESUMO

The interference screw fixation method is used to secure a graft in the tibial tunnel during anterior cruciate ligament reconstruction surgery. However, several complications have been reported, such as biodegradable screw breakage, inflammatory or foreign body reaction, tunnel enlargement, and delayed graft healing. Using additive manufacturing (AM) technology, we developed a titanium alloy (Ti6Al4V) interference screw with chemically calcium phosphate surface modification technology to improve bone integration in the tibial tunnel. After chemical and heat treatment, the titanium screw formed a dense apatite layer on the metal surface in simulated body fluid. Twenty-seven New Zealand white rabbits were randomly divided into control and additive manufactured (AMD) screw groups. The long digital extensor tendon was detached and translated into a tibial plateau tunnel (diameter: 2.0 mm) and transfixed with an interference screw while the paw was in dorsiflexion. Biomechanical analyses, histological analyses, and an imaging study were performed at 1, 3, and 6 months. The biomechanical test showed that the ultimate pull-out load failure was significantly higher in the AMD screw group in all tested periods. Micro-computed tomography analyses revealed early woven bone formation in the AMD screw group at 1 and 3 months. In conclusion, AMD screws with bioactive surface modification improved bone ingrowth and enhanced biomechanical performance in a rabbit model.


Assuntos
Parafusos Ósseos/normas , Osseointegração , Impressão Tridimensional , Tendões/cirurgia , Tíbia/cirurgia , Ligas/química , Animais , Parafusos Ósseos/efeitos adversos , Interface Osso-Implante/cirurgia , Fosfatos de Cálcio/química , Porosidade , Coelhos
8.
J Formos Med Assoc ; 119(1 Pt 3): 420-429, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31387841

RESUMO

BACKGROUND/PURPOSE: Alveolar bone loss following peri-implantitis remains a clinical challenge. We aimed to design a novel bioactive dental implant to accommodate the large bone defect caused by removal of previously failed implant. METHODS: Bio-ActiveITRI dental implant was manufactured with laser-sintered additive 3D printing technique. A 7.5 mm diameter × 7.0 mm depth osteotomy defect was created at the lateral aspect of distal femur of 20 New Zealand white rabbits to simulate the bony defect after removal of failed dental implant. One side of distal femurs was randomly selected for the commercially pure titanium NobelActive™ implant (control group) and the other side with Bio-ActiveITRI Ti6Al4V porous dental implant (ITRI group). Animals were sacrificed at 4, 8 and 12 weeks after the implants' insertion. The samples were processed for gross morphological analysis, radiographic examination, micro-CT evaluation, and mechanical testing. RESULTS: In histomorphometrical evaluation and micro-CT analysis, active new bone formation and good osseointegration within the ITRI implants were observed at the bone gap surrounding the dental implants. The biomechanical parameters in the Bio-ActiveITRI dental implants were significantly higher than those of the commercially control samples. For the Bio-ActiveITRI dental implants, the trabecular thickness decreased, while the trabecular separation and total porosity increased from the prescribed 1-month to 3-month time points; reflecting the natural remodeling of surrounding bony tissue in the Bio-ActiveITRI dental implants. CONCLUSION: The novel porous structured Bio-ActiveITRI dental implants may have a great potential for the prosthetic reconstruction where bone support is compromised after removal of a previously failed implant.


Assuntos
Implantes Dentários , Fêmur/cirurgia , Lasers , Osseointegração/fisiologia , Impressão Tridimensional , Titânio/química , Animais , Teste de Materiais , Porosidade , Coelhos , Propriedades de Superfície , Titânio/efeitos da radiação , Microtomografia por Raio-X
9.
Sci Rep ; 9(1): 2317, 2019 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-30783144

RESUMO

Chronic inflammation is a pivotal event in the pathogenesis of cardiovascular diseases, including atherosclerosis, restenosis, and coronary artery disease. The efficacy of current treatment or preventive strategies for such inflammation is still inadequate. Thus, new anti-inflammatory strategies are needed. In this study, based on molecular docking and structural analysis, a potential peptide KCF18 with amphiphilic properties (positively charged and hydrophobic residues) derived from the receptors of proinflammatory cytokines was designed to inhibit cytokine-induced inflammatory response. Simulations suggested that KCF18 could bind to cytokines simultaneously, and electrostatic interactions were dominant. Surface plasmon resonance detection showed that KCF18 bound to both tumor necrosis factor-α (TNF-α) and interleukin-6, which is consistent with MM/PBSA binding free energy calculations. The cell experiments showed that KCF18 significantly reduced the binding of proinflammatory cytokines to their cognate receptors, suppressed TNF-α mRNA expression and monocyte binding and transmigration, and alleviated the infiltration of white blood cells in a peritonitis mouse model. The designed peptide KCF18 could remarkably diminish the risk of vascular inflammation by decreasing plasma cytokines release and by directly acting on the vascular endothelium. This study demonstrated that a combination of structure-based in silico design calculations, together with experimental measurements can be used to develop potential anti-inflammatory agents.


Assuntos
Inflamação/tratamento farmacológico , Inflamação/metabolismo , Peptídeos/química , Peptídeos/uso terapêutico , Receptores de Citocinas/química , Humanos , Interleucina-1beta/metabolismo , Interleucina-1beta/farmacologia , Interleucina-6/metabolismo , Interleucina-6/farmacologia , Ligação Proteica , Células THP-1 , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/farmacologia
10.
Materials (Basel) ; 12(1)2019 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-30621012

RESUMO

A mismatch of elastic modulus values could result in undesirable bone resorption around the dental implant. The objective of this study was to optimize direct metal laser sintering (DMLS)-manufactured Ti6Al4V dental implants' design, minimize elastic mismatch, allow for maximal bone ingrowth, and improve long-term fixation of the implant. In this study, DMLS dental implants with different morphological characteristics were fabricated. Three-point bending, torsional, and stability tests were performed to compare the mechanical properties of different designs. Improvement of the weaker design was attempted by augmentation with a longitudinal 3D-printed strut. The osseointegrative properties were evaluated. The results showed that the increase in porosity decreased the mechanical properties, while augmentation with a longitudinal weight-bearing strut can improve mechanical strength. Maximal alkaline phosphatase gene expression of MG63 cells attained on 60% porosity Ti6Al4V discs. In vivo experiments showed good incorporation of bone into the porous scaffolds of the DMLS dental implant, resulting in a higher pull-out strength. In summary, we introduced a new design concept by augmenting the implant with a longitudinal weight-bearing strut to achieve the ideal combination of high strength and low elastic modulus; our results showed that there is a chance to reach the balance of both biologic and mechanical demands.

11.
J Orthop Res ; 36(10): 2633-2640, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29727018

RESUMO

The interference screw is a widely used fixation device in the anterior cruciate ligament (ACL) reconstruction surgeries. Despite the generally satisfactory results, problems of using interference screws were reported. By using additive manufacturing (AM) technology, we developed an innovative titanium alloy (Ti6 Al4 V) interference screw with rough surface and inter-connected porous structure designs to improve the bone-tendon fixation. An innovative Ti6 Al4 V interference screws were manufactured by AM technology. In vitro mechanical tests were performed to validate its mechanical properties. Twenty-seven New Zealand white rabbits were randomly divided into control and AM screw groups for biomechanical analyses and histological analysis at 4, 8, and 12 weeks postoperatively; while micro-CT analysis was performed at 12 weeks postoperatively. The biomechanical tests showed that the ultimate failure load in the AM interference screw group was significantly higher than that in the control group at all tested periods. These results were also compatible with the findings of micro-CT and histological analyses. In micro-CT analysis, the bone-screw gap was larger in the control group; while for the additive manufactured screw, the screw and bone growth was in close contact. In histological study, the bone-screw gaps were wider in the control group and were almost invisible in the AM screw group. The innovative AM interference screws with surface roughness and inter-connected porous architectures demonstrated better bone-tendon-implant integration, and resulted in stronger biomechanical characteristics when compared to traditional screws. These advantages can be transferred to future interference screw designs to improve their clinical performance. The AM interference screw could improve graft fixation and eventually result in better biomechanical performance of the bone-tendon-screw construct. The innovative AM interference screws can be transferred to future interference screw designs to improve the performance of implants. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2633-2640, 2018.


Assuntos
Reconstrução do Ligamento Cruzado Anterior/instrumentação , Parafusos Ósseos , Tendões/cirurgia , Animais , Fenômenos Biomecânicos , Porosidade , Coelhos , Distribuição Aleatória , Titânio , Microtomografia por Raio-X
12.
Mol Cell ; 69(5): 744-756.e6, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29456190

RESUMO

Mitochondrial crista structure partitions vital cellular reactions and is precisely regulated by diverse cellular signals. Here, we show that, in Drosophila, mitochondrial cristae undergo dynamic remodeling among distinct subcellular regions and the Parkinson's disease (PD)-linked Ser/Thr kinase PINK1 participates in their regulation. Mitochondria increase crista junctions and numbers in selective subcellular areas, and this remodeling requires PINK1 to phosphorylate the inner mitochondrial membrane protein MIC60/mitofilin, which stabilizes MIC60 oligomerization. Expression of MIC60 restores crista structure and ATP levels of PINK1-null flies and remarkably rescues their behavioral defects and dopaminergic neurodegeneration. In an extension to human relevance, we discover that the PINK1-MIC60 pathway is conserved in human neurons, and expression of several MIC60 coding variants in the mitochondrial targeting sequence found in PD patients in Drosophila impairs crista junction formation and causes locomotion deficits. These findings highlight the importance of maintenance and plasticity of crista junctions to cellular homeostasis in vivo.


Assuntos
Proteínas de Drosophila/metabolismo , Membranas Mitocondriais/metabolismo , Neurônios/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Animais , Proteínas de Drosophila/genética , Drosophila melanogaster , Humanos , Membranas Mitocondriais/patologia , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Neurônios/patologia , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Fosforilação/genética , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética
13.
Mol Biol Cell ; 28(24): 3471-3479, 2017 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-28904209

RESUMO

MIC60/mitofilin constitutes a hetero-oligomeric complex on the inner mitochondrial membranes to maintain crista structure. However, little is known about its physiological functions. Here, by characterizing Drosophila MIC60 mutants, we define its roles in vivo. We discover that MIC60 performs dual functions to maintain mitochondrial homeostasis. In addition to its canonical role in crista membrane structure, MIC60 regulates mitochondrial motility, likely by influencing protein levels of the outer mitochondrial membrane protein Miro that anchors mitochondria to the microtubule motors. Loss of MIC60 causes loss of Miro and mitochondrial arrest. At a cellular level, loss of MIC60 disrupts synaptic structure and function at the neuromuscular junctions. The dual roles of MIC60 in both mitochondrial crista structure and motility position it as a crucial player for cellular integrity and survival.


Assuntos
Proteínas de Drosophila/metabolismo , Mitocôndrias/fisiologia , Membranas Mitocondriais/metabolismo , Proteínas Mitocondriais/metabolismo , Proteínas Musculares/metabolismo , Animais , Movimento Celular/fisiologia , Drosophila , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Membranas Mitocondriais/fisiologia , Junção Neuromuscular/metabolismo , Junção Neuromuscular/fisiologia
14.
BMC Infect Dis ; 17(1): 516, 2017 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-28743235

RESUMO

BACKGROUND: When bacteria colony persist within a biofilm, suitable drugs are not yet available for the eradication of biofilm-producing bacteria. The aim of this study is to study the effect of magnetic nano-particles-induced hyperthermia on destroying biofilm and promoting bactericidal effects of antibiotics in the treatment of osteomyelitis. METHODS: Sixty 12-weeks-old male Wistar rats were used. A metallic 18G needle was implanted into the bone marrow cavity of distal femur after the injection of Methicillin-sensitive Staphylococcus aureus (MSSA). All animals were divided into 5 different treatment modalities. The microbiological evaluation, scanning electron microscope examination, radiographic examination and then micro-CT evaluation of peri-implant bone resorption were analyzed. RESULTS: The pathomorphological characteristics of biofilm formation were completed after 40-days induction of osteomyelitis. The inserted implants can be heated upto 75 °C by magnetic heating without any significant thermal damage on the surrounding tissue. We also demonstrated that systemic administration of vancomycin [VC (i.m.)] could not eradicate the bacteria; but, local administration of vancomycin into the femoral canal and the presence of magnetic nanoparticles hyperthermia did enhance the eradication of bacteria in a biofilm-based colony. In these two groups, the percent bone volume (BV/TV: %) was significantly higher than that of the positive control. CONCLUSIONS: For the treatment of chronic osteomyelitis, we developed a new modality to improve antibiotic efficacy; the protection effect of biofilms on bacteria could be destroyed by magnetic nanoparticles-induced hyperthermia and therapeutic effect of systemic antibiotics could be enhanced.


Assuntos
Antibacterianos/farmacologia , Hipertermia Induzida/métodos , Osteomielite/terapia , Infecções Relacionadas à Prótese/terapia , Infecções Estafilocócicas/terapia , Animais , Biofilmes , Hipertermia Induzida/instrumentação , Nanopartículas de Magnetita , Masculino , Staphylococcus aureus Resistente à Meticilina , Osteomielite/microbiologia , Ratos Wistar , Infecções Estafilocócicas/microbiologia , Resultado do Tratamento , Vancomicina/farmacologia
15.
Biomed Res Int ; 2017: 1970680, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28293628

RESUMO

The inclusion of a healing chamber in dental implants has been shown to promote biological healing. In this paper, a novel numerical approach to the design of the healing chamber for additive-manufactured dental implants is proposed. This study developed an algorithm for the modeling of bone growth and employed finite element method in ANSYS to facilitate the design of healing chambers with a highly complex configuration. The model was then applied to the design of dental implants for insertion into the posterior maxillary bones. Two types of ITI® solid cylindrical screwed implant with extra rectangular-shaped healing chamber as an initial design are adopted, with which to evaluate the proposed system. This resulted in several configurations for the healing chamber, which were then evaluated based on the corresponding volume fraction of healthy surrounding bone. The best of these implants resulted in a healing chamber surrounded by around 9.2% more healthy bone than that obtained from the original design. The optimal design increased the contact area between the bone and implant by around 52.9%, which is expected to have a significant effect on osseointegration. The proposed approach is highly efficient which typically completes the optimization of each implant within 3-5 days on an ordinary personal computer. It is also sufficiently general to permit extension to various loading conditions.


Assuntos
Implantes Dentários , Planejamento de Prótese Dentária/métodos , Algoritmos , Parafusos Ósseos , Osso e Ossos/patologia , Análise do Estresse Dentário/métodos , Análise de Elementos Finitos , Humanos , Imageamento Tridimensional , Modelos Teóricos , Osseointegração
16.
Neuromethods ; 123: 49-66, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29977105

RESUMO

Mitochondria are among a cell's most vital organelles. They not only produce the majority of the cell's ATP but also play a key role in Ca2+ buffering and apoptotic signaling. While proper allocation of mitochondria is critical to all cells, it is particularly important for the highly polarized neurons. Because mitochondria are mainly synthesized in the soma, they must be transported long distances to be distributed to the far-flung reaches of the neuron-up to 1 m in the case of some human motor neurons. Furthermore, damaged mitochondria can be detrimental to neuronal health, causing oxidative stress and even cell death, therefore the retrograde transport of damaged mitochondria back to the soma for proper disposal, as well as the anterograde transport of fresh mitochondria from the soma to repair damage, are equally critical. Intriguingly, errors in mitochondrial transport have been increasingly implicated in neurological disorders. Here, we describe how to investigate mitochondrial transport in three complementary neuronal systems: cultured induced pluripotent stem cell-derived neurons, cultured rat hippocampal and cortical neurons, and Drosophila larval neurons in vivo. These models allow us to uncover the molecular and cellular mechanisms underlying transport issues that may occur under physiological or pathological conditions.

17.
PLoS Genet ; 12(10): e1006362, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27736876

RESUMO

In response to environmental and physiological changes, the synapse manifests plasticity while simultaneously maintains homeostasis. Here, we analyzed mutant synapses of henji, also known as dbo, at the Drosophila neuromuscular junction (NMJ). In henji mutants, NMJ growth is defective with appearance of satellite boutons. Transmission electron microscopy analysis indicates that the synaptic membrane region is expanded. The postsynaptic density (PSD) houses glutamate receptors GluRIIA and GluRIIB, which have distinct transmission properties. In henji mutants, GluRIIA abundance is upregulated but that of GluRIIB is not. Electrophysiological results also support a GluR compositional shift towards a higher IIA/IIB ratio at henji NMJs. Strikingly, dPAK, a positive regulator for GluRIIA synaptic localization, accumulates at the henji PSD. Reducing the dpak gene dosage suppresses satellite boutons and GluRIIA accumulation at henji NMJs. In addition, dPAK associated with Henji through the Kelch repeats which is the domain essential for Henji localization and function at postsynapses. We propose that Henji acts at postsynapses to restrict both presynaptic bouton growth and postsynaptic GluRIIA abundance by modulating dPAK.


Assuntos
Proteínas de Drosophila/genética , Junção Neuromuscular/genética , Receptores de Glutamato/genética , Receptores Ionotrópicos de Glutamato/genética , Sinapses/genética , Quinases Ativadas por p21/genética , Animais , Moléculas de Adesão Celular Neuronais/genética , Drosophila melanogaster/genética , Drosophila melanogaster/ultraestrutura , Repetição Kelch/genética , Microscopia Eletrônica de Transmissão , Junção Neuromuscular/ultraestrutura , Terminações Pré-Sinápticas/metabolismo , Sinapses/ultraestrutura , Transmissão Sináptica/genética
18.
PLoS One ; 11(7): e0160031, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27459633

RESUMO

For rapid screening and quantification of an antisera antibody, a nanometer bithiophene-based conductive biolinker can enhanced signal performance and can be used to verify the interaction of an anti-IFN-γ antibody with an IFN-γ protein. The experimental measurements take a generic approach which takes advantage of the functionality of thiophene-based linkers for biosensors. Effects associated with using bithiophene as a biolinker for surface plasmon resonance (SPR) spectroscopy are examined in this paper. By using an atomic force microscope (AFM), it was observed that the morphology of the bithiophene modified gold sensor surface became smoother than the original gold surface. We compared the response and concentration of the anti-IFN-γ antibody on a bithiophene-coated and dextran-coated biochip as well as on different thickness-modified surfaces under SPR relevant conditions. The results indicate that a response to IFN-γ molecules immobilized on a sensor using a bithiophene biolinker improved more than 8-fold when compared to that of a sensor using a dextran biolinker. Furthermore, the regeneration ability of the sensor surface shows good repeatability as only less than a 1% decrease was found after repeating the experimental work over 6 cycles. The characteristics provided us with a good platform for rapid screening, real-time monitoring and quantitative concentration of the autoimmune antibody activities.


Assuntos
Anticorpos/imunologia , Técnicas Biossensoriais/métodos , Interferon gama/imunologia , Nanotecnologia/métodos , Animais , Anticorpos/análise , Dextranos/química , Ouro/química , Humanos , Proteínas Imobilizadas/imunologia , Camundongos , Sensibilidade e Especificidade , Tiofenos/química
19.
Comput Biol Med ; 76: 14-23, 2016 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-27392226

RESUMO

Traditional solid cages have been widely used in posterior lumbar interbody fusion (PLIF) surgery. However, solid cages significantly affect the loading mechanism of the human spine due to their extremely high structural stiffness. Previous studies proposed and investigated porous additive manufactured (AM) cages; however, their biomechanical performances were analyzed using oversimplified bone-implant numerical models. Thus, the aim of this study was to investigate the outer shape and inner porous structure of the AM cages. The outer shape of the AM cages was discovered using a simulation-based genetic algorithm; their inner porous structure was subsequently analyzed parametrically using T10-S1 multilevel spine models. Finally, six types of the AM cages, which were manufactured using selective laser melting, were tested to validate the numerical outcomes. The subsidence resistance of the optimum design was superior to the conventional cage designs. A porous AM cage with a pillar diameter of 0.4mm, a pillar angle of 40°, and a porosity of between 69% and 80% revealed better biomechanical performances. Both the numerical and experimental outcomes can help surgeons to understand the biomechanics of PLIF surgery combined with the use of AM cages.


Assuntos
Fenômenos Biomecânicos/fisiologia , Fixadores Internos , Modelos Biológicos , Fusão Vertebral/instrumentação , Simulação por Computador , Análise de Elementos Finitos , Humanos , Vértebras Lombares/fisiologia , Vértebras Lombares/cirurgia , Porosidade , Desenho de Prótese
20.
Sci Rep ; 4: 6962, 2014 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-25376463

RESUMO

Mutations in the mitochondrial Ser/Thr kinase PINK1 cause Parkinson's disease. One of the substrates of PINK1 is the outer mitochondrial membrane protein Miro, which regulates mitochondrial transport. In this study, we uncovered novel physiological functions of PINK1-mediated phosphorylation of Miro, using Drosophila as a model. We replaced endogenous Drosophila Miro (DMiro) with transgenically expressed wildtype, or mutant DMiro predicted to resist PINK1-mediated phosphorylation. We found that the expression of phospho-resistant DMiro in a DMiro null mutant background phenocopied a subset of phenotypes of PINK1 null. Specifically, phospho-resistant DMiro increased mitochondrial movement and synaptic growth at larval neuromuscular junctions, and decreased the number of dopaminergic neurons in adult brains. Therefore, PINK1 may inhibit synaptic growth and protect dopaminergic neurons by phosphorylating DMiro. Furthermore, muscle degeneration, swollen mitochondria and locomotor defects found in PINK1 null flies were not observed in phospho-resistant DMiro flies. Thus, our study established an in vivo platform to define functional consequences of PINK1-mediated phosphorylation of its substrates.


Assuntos
Encéfalo/metabolismo , Neurônios Dopaminérgicos/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Mitocôndrias/metabolismo , Junção Neuromuscular/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas rho de Ligação ao GTP/metabolismo , Animais , Animais Geneticamente Modificados , Encéfalo/patologia , Modelos Animais de Doenças , Neurônios Dopaminérgicos/patologia , Proteínas de Drosophila/deficiência , Drosophila melanogaster/genética , Regulação da Expressão Gênica , Humanos , Larva/genética , Larva/metabolismo , Locomoção/genética , Mitocôndrias/genética , Mitocôndrias/patologia , Doenças Mitocondriais/genética , Doenças Mitocondriais/metabolismo , Doenças Mitocondriais/patologia , Músculos/metabolismo , Músculos/patologia , Mutação , Junção Neuromuscular/genética , Junção Neuromuscular/patologia , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Fenótipo , Fosforilação , Proteínas Serina-Treonina Quinases/deficiência , Transdução de Sinais , Sinapses/metabolismo , Sinapses/patologia , Proteínas rho de Ligação ao GTP/genética
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