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1.
Food Chem ; 453: 139626, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-38759440

RESUMO

Ethyl carbamate (EC) is a carcinogen widely found in the fermentation process of Baijiu. Herein, we construct a molecularly imprinted polymers/MXene/cobalt (II) based zeolitic imidazolate frameworks (MIP/MXene/ZIF-67) nano-enzyme sensor for the detection of EC during Baijiu production. The ZIF-67 is synthesized in situ on the MXene nanosheets to provide a superior catalytic activity to H2O2 and amplify the electrochemical signal. The MIP is prepared by the polymerization reaction to recognize EC. Owing to the interaction between EC and EC-MIP, the interferences are effectively eliminated, greatly improving the accuracy of the expected outcome. This approach attains an ultrasensitive assay of EC ranging from 8.9 µg/L to 44.5 mg/L with detection limit of 0.405 µg/L. The accuracy of this method is confirmed by the recovery experiment with good recoveries from 95.07% to 107.41%. This method is applied in natural EC analyses, and the results are consistent with certified gas chromatograph- mass spectrometer.


Assuntos
Técnicas Eletroquímicas , Contaminação de Alimentos , Impressão Molecular , Uretana , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Uretana/análise , Uretana/química , Contaminação de Alimentos/análise , Catálise , Polímeros Molecularmente Impressos/química , Limite de Detecção
2.
J Biomed Mater Res A ; 112(9): 1424-1435, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38465895

RESUMO

Currently available focal knee resurfacing implants (FKRIs) are fully or partially composed of metals, which show a large disparity in elastic modulus relative to bone and cartilage tissue. Although titanium is known for its excellent osseointegration, the application in FKRIs can lead to potential stress-shielding and metal implants can cause degeneration of the opposing articulating cartilage due to the high resulting contact stresses. Furthermore, metal implants do not allow for follow-up using magnetic resonance imaging (MRI).To overcome the drawbacks of using metal based FKRIs, a biomimetic and MRI compatible bi-layered non-resorbable thermoplastic polycarbonate-urethane (PCU)-based FKRI was developed. The objective of this preclinical study was to evaluate the mechanical properties, biocompatibility and osteoconduction of a novel Bionate® 75D - zirconium oxide (B75D-ZrO2) composite material in vitro and the osseointegration of a B75D-ZrO2 composite stem PCU implant in a caprine animal model. The tensile strength and elastic modulus of the B75D-ZrO2 composite were characterized through in vitro mechanical tests under ambient and physiological conditions. In vitro biocompatibility and osteoconductivity were evaluated by exposing human mesenchymal stem cells to the B75D-ZrO2 composite and culturing the cells under osteogenic conditions. Cell activity and mineralization were assessed and compared to Bionate® 75D (B75D) and titanium disks. The in vivo osseointegration of implants containing a B75D-ZrO2 stem was compared to implants with a B75D stem and titanium stem in a caprine large animal model. After a follow-up of 6 months, bone histomorphometry was performed to assess the bone-to-implant contact area (BIC). Mechanical testing showed that the B75D-ZrO2 composite material possesses an elastic modulus in the range of the elastic modulus reported for trabecular bone. The B75D-ZrO2 composite material facilitated cell mediated mineralization to a comparable extent as titanium. A significantly higher bone-to-implant contact (BIC) score was observed in the B75D-ZrO2 implants compared to the B75D implants. The BIC of B75D-ZrO2 implants was not significantly different compared to titanium implants. A biocompatible B75D-ZrO2 composite approximating the elastic modulus of trabecular bone was developed by compounding B75D with zirconium oxide. In vivo evaluation showed an significant increase of osseointegration for B75D-ZrO2 composite stem implants compared to B75D polymer stem PCU implants. The osseointegration of B75D-ZrO2 composite stem PCU implants was not significantly different in comparison to analogous titanium stem metal implants.


Assuntos
Teste de Materiais , Osseointegração , Cimento de Policarboxilato , Uretana , Zircônio , Zircônio/química , Zircônio/farmacologia , Animais , Osseointegração/efeitos dos fármacos , Uretana/química , Cimento de Policarboxilato/química , Prótese do Joelho , Humanos , Cabras , Materiais Biocompatíveis/química , Células-Tronco Mesenquimais/citologia
3.
Org Biomol Chem ; 20(16): 3303-3310, 2022 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-35229099

RESUMO

This study demonstrated the rapid dual activation (10 s, 20 °C) of a combination of an α-amino acid N-carboxyanhydride and alkyl chloroformate in the synthesis of a urethane-protected α-amino acid N-carboxyanhydride in a micro-flow reactor. The key to success was the combined use of two amines that activated both substrates with proper timing. Three amines, i-Pr2NEt, Me2NBn, or N-ethylmorpholine, were used with pyridine in accordance with the steric bulkiness of a side chain in the α-amino acid N-carboxyanhydride. A variety of 16 urethane-protected α-amino acid N-carboxyanhydrides were synthesized in high yields. The role of amines was investigated based on the measurement of the time-dependent (0.5 to 10 s) decrease of α-amino acid N-carboxyanhydrides and alkyl chloroformates in the presence of amines via flash mixing technology using a micro-flow reactor. It was suggested that the in situ generated acylpyridinium cation was highly active and less prone to causing undesired decomposition compared with the acylammonium cation examined in this study. Thus, even at a very low concentration, the acylpyridinium cation facilitated the desired coupling reaction.


Assuntos
Peptídeos , Uretana , Amidas , Aminas , Aminoácidos/química , Ésteres , Peptídeos/química , Uretana/química
4.
J Mater Sci Mater Med ; 32(8): 85, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34297226

RESUMO

Cerebrospinal fluid leakage is a frequent complication after cranial and spinal surgery. To prevent this complication and seal the dura watertight, we developed Liqoseal, a dural sealant patch comprising a watertight polyesterurethane layer and an adhesive layer consisting of poly(DL-lactide-co-ε-caprolactone) copolymer and multiarmed N-hydroxylsuccinimide functionalized polyethylene glycol. We compared acute burst pressure and resistance to physiological conditions for 72 h of Liqoseal, Adherus, Duraseal, Tachosil, and Tisseel using computer-assisted models and fresh porcine dura. The mean acute burst pressure of Liqoseal in the cranial model (145 ± 39 mmHg) was higher than that of Adherus (87 ± 47 mmHg), Duraseal (51 ± 42 mmHg) and Tachosil (71 ± 16 mmHg). Under physiological conditions, cranial model resistance test results showed that 2 of 3 Liqoseal sealants maintained dural attachment during 72 hours as opposed to 3 of 3 for Adherus and Duraseal and 0 of 3 for Tachosil. The mean burst pressure of Liqoseal in the spinal model (233 ± 81 mmHg) was higher than that of Tachosil (123 ± 63 mmHg) and Tisseel (23 ± 16 mmHg). Under physiological conditions, spinal model resistance test results showed that 2 of 3 Liqoseal sealants maintained dural attachment for 72 hours as opposed to 3 of 3 for Adherus and 0 of 3 for Duraseal and Tachosil. This novel study showed that Liqoseal is capable of achieving a strong watertight seal over a dural defect in ex vivo models.


Assuntos
Procedimentos Neurocirúrgicos/métodos , Animais , Encéfalo , Caproatos/química , Vazamento de Líquido Cefalorraquidiano/prevenção & controle , Combinação de Medicamentos , Dura-Máter/cirurgia , Desenho de Equipamento , Adesivo Tecidual de Fibrina/química , Fibrinogênio/química , Humanos , Técnicas In Vitro , Lactonas/química , Poliésteres/química , Polietilenoglicóis/química , Polímeros/química , Poliuretanos , Resinas Sintéticas , Crânio , Medula Espinal/cirurgia , Succinimidas/química , Suínos , Trombina/química , Adesivos Teciduais , Uretana/química
5.
Arch Gynecol Obstet ; 303(1): 181-188, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33146769

RESUMO

PURPOSE: Postoperative seromas are a problem in the surgical treatment of breast cancer. The aim of the study was to evaluate whether the lysine-urethane-based tissue adhesive TissuGlu® without drainage is equal/ non-inferior to standard mastecomy with drainage. METHODS: The study was designed as a prospective, randomized, multicentre non-inferiority study comparing the use of TissuGlu® without drainage with standard wound care with a drain insertion in ablative breast procedures. The number of clinical interventions, quality of life and wound complications were followed-up for 90 days in both groups. RESULTS: Although the statistical power was not reached, twice as many clinical interventions were performed in the TissuGlu® group than in the drainage group, especially aspirations of clinically relevant seromas (p = 0.014). The TissuGlu® group produced overall less wound fluid, but developed a clinically relevant seroma (100% vs. 63%) which made an intervention necessary. Less hospitalisation time was observed in the TissuGlu® group, but the complication rate was higher. There was no significant difference in regards to postoperative pain. In summary the non-inferiority of TissuGlu® compared to standard drainage couldn't be reached. DISCUSSION: The present evaluation shows no advantage of the tissue adhesive TissuGlu® in terms of seroma formation and frequency of intervention compared to a standard drainage for mastectomies, but the shorter inpatient stay certainly has a positive effect on the quality of life.


Assuntos
Neoplasias da Mama/cirurgia , Mastectomia/métodos , Procedimentos de Cirurgia Plástica/efeitos adversos , Seroma/prevenção & controle , Fita Cirúrgica , Técnicas de Sutura/efeitos adversos , Adesivos Teciduais/uso terapêutico , Adulto , Neoplasias da Mama/patologia , Drenagem/métodos , Feminino , Humanos , Lisina/química , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Qualidade de Vida , Seroma/epidemiologia , Seroma/etiologia , Aderências Teciduais , Adesivos Teciduais/química , Resultado do Tratamento , Uretana/química
6.
Food Chem ; 343: 128528, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33189477

RESUMO

Ethyl carbamate (EC), a genotoxic and carcinogenic compound in soy sauce accumulated during thermal processes, has raised public health concern for its multipoint potential carcinogenic risk to human. In this work, based on the analysis of EC accumulation during thermal processes of soy sauce, ornithine and quercetin were added before thermal processes to reduce EC accumulation. A reduction rate of 23.7-63.8% in simulated solution was founded. Kinetic studies indicated that ornithine was a byproduct of alcoholysis reaction when EC formed, while quercetin could compete with the precursor ethanol and react with carbamyl compounds, which therefore preventedEC accumulation. A maximum of 47.2% decrease of EC in soy sauce was achieved, and no remarkable changes in volatile compounds profile and color of soy sauce were found. In conclusion, the addition of quercetin and ornithine before thermal processes may be preferable for the controlling of EC content in soy sauce.


Assuntos
Ornitina/química , Quercetina/química , Alimentos de Soja , Uretana/química , Carcinógenos/química , Etanol/química , Fermentação , Qualidade dos Alimentos , Humanos , Concentração de Íons de Hidrogênio , Cinética , Alimentos de Soja/análise , Uretana/análise
7.
J Biomed Mater Res B Appl Biomater ; 109(5): 693-702, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33098257

RESUMO

Surgical sutures are indispensable for a vast majority of operative procedures. An ideal suture is characterized by high tissue compliance without cutting into the mended tissue and optimal biocompatibility. Therefore, we assessed these mechanical and biological properties for novel elastic thermoplastic polyurethane (TPU) and cross-sectional modified "snowflake" sutures. Circular and "snowflake"-shaped TPU threads were manufactured and compared to similar surface modified polyvinylidene fluoride (PVDF) sutures. Regular PVDF sutures were used as the control group. Single-axis tensile test with and without gelatinous tissue surrogates were performed to evaluate the suture incision into the specimens. Biocompatibility was evaluated by subcutaneous implantation (n = 18) in rats for 7 and 21 days. Histology and immunohistology was conducted for assessment of the foreign body reaction. Regular and modified TPU threads showed a significant reduction of incision into the tissue surrogates compared to the control. Both TPU sutures and the modified PVDF sutures achieved comparable biocompatibility versus regular PVDF threads. Detailed histology revealed novel tissue integration into the notches of the surface modified sutures, we termed this newly shaped granuloma "intrafilamentous" granuloma. Elastic TPU threads showed a significant reduction of tissue surrogate incision and suture tension loss. Biocompatibility did not significantly differ from standard PVDF. Histology demonstrated tissue ingrowth following the surface modification of the suture referred to as "intrafilamentous" granuloma. Further in vivo studies are required to illuminate the exact potential of the new sutures to optimize intestinal anastomosis.


Assuntos
Materiais Biocompatíveis/química , Elasticidade , Suturas , Uretana/química , Animais , Desenho de Equipamento , Feminino , Polímeros de Fluorcarboneto/química , Reação a Corpo Estranho , Granuloma/patologia , Técnicas In Vitro , Teste de Materiais , Polímeros/química , Polivinil/química , Ratos , Ratos Sprague-Dawley , Temperatura , Resistência à Tração
8.
Biomed Res Int ; 2020: 2981681, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33274201

RESUMO

Ethyl-4-bromophenyl-carbamate (LQM 919) and Ethyl-4-chlorophenyl-carbamate (LQM 996) are compounds that inhibit egg-laying and hatching of tick larvae that are resistant to conventional ixodicides. The structure-activity relationship (SAR) to get the endpoint predictions of mutagenicity and carcinogenicity of the LQM 919 and LQM 996 was performed and the absence of mutagenicity was confirmed by Ames test. SAR analysis show no structural alerts indicating the ability of ethyl-carbamates to bind biomolecules or estrogen receptors. Endpoint of mutagenicity with and without metabolic activation showed that the ethyl-carbamates were negative (p <0.05) for mutagenicity induction in strains TA97, TA98, TA102, TA1535, TA1537 and TA1538 of Salmonella typhimurium. Pre-incubation with different ethyl-carbamate concentrations did not increase the number of spontaneously reverting colonies; moreover, the compounds did not induce a concentration-dependent increase in the number of reverting colonies in any of the strains used. This confirmed the absence of mutagenic activity in this test system. Exogenous metabolic activation did not modify these observations; suggesting that no metabolites with mutagenic activity were present. The endpoint of carcinogenicity in rats were negative for LQM 919 (p <0.05,) and LQM 996 (p <0.001). The results of the present study strongly suggest that ethyl-carbamates do not represent a risk for cancer in mammals.


Assuntos
Carcinógenos/química , Carcinógenos/toxicidade , Ixodidae/efeitos dos fármacos , Mutagênicos/química , Mutagênicos/toxicidade , Uretana/química , Uretana/toxicidade , Animais , Salmonella typhimurium/efeitos dos fármacos , Relação Estrutura-Atividade
9.
Food Funct ; 11(12): 10317-10328, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33215619

RESUMO

Ethyl carbamate (EC) is an environmental toxin, commonly present in various fermented foods and beverages, as well as tobacco and polluted ambient air. However, studies on the effects of EC-induced toxicity on the intestines and potential protection methods are limited. In this study, we show that EC could cause severe toxicity in intestinal epithelial cells (IECs) triggering the induction of decreased cell viability, ROS accumulation and glutathione (GSH) depletion in a dose-dependent manner. Based on these results, we established an EC-treated IEC model to screen the potential protective effects of 12 kinds of anthocyanins extracted from blueberry. Interestingly, we found that malvidin-3-O-arabinoside (M3A) significantly reversed the oxidative damage caused by EC exposure by stimulating autophagy flux, which was determined by the LC3-II level and GFP-RFP-LC3 transfection experiment. Enhancement of autophagy was mainly ascribed to the regulation of lysosomes. M3A pretreatment remarkably upregulated LAMP-1 expression, which indicated elevated lysosomal mass. Besides, M3A also successfully restored lysosomal acidity and subsequently strengthened lysosomal functions. Furthermore, M3A stimulated phosphorylation of AMP-activated protein kinase (AMPK), a master regulator of autophagy. Furthermore, our study indicated the possibility of EC-caused oxidative damage to the intestines and unveiled the remarkably protective benefits of M3A-induced AMPK-mediated autophagy against this toxicity.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Antocianinas/farmacologia , Autofagia/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Uretana/farmacologia , Antocianinas/química , Células CACO-2 , Sobrevivência Celular/efeitos dos fármacos , Glutationa/metabolismo , Humanos , Intestinos , Lisossomos/metabolismo , Simulação de Acoplamento Molecular , Fosforilação , Espécies Reativas de Oxigênio/metabolismo , Regulação para Cima , Uretana/química
10.
J Mater Chem B ; 8(18): 4106-4121, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-32253395

RESUMO

In the tissue engineering of cartilage, scaffolds with appropriate elasticity and controlled-release properties are essential. Herein, we synthesized a poly(ether-ester-urethane)urea scaffold with a pendant amino group (PEEUUN) through a de-protection process from PEEUU-Boc polymers and grafted kartogenin (KGN) onto the PEEUUN scaffolds (PEEUUN-KGN). Characterization, performance tests, scaffold biocompatibility analysis, and chondrogenesis evaluation both in vitro and in vivo were conducted. The results revealed that the PEEUUN-KGN scaffolds were degradable and three-dimensional (3D) with interconnected pores, and possessed good elasticity, as well as excellent cytocompatibility. Meanwhile, KGN on the PEEUUN-KGN scaffolds underwent stable sustained release for a long time and promoted human umbilical cord mesenchymal stem cells (HUCMSCs) to differentiate into chondrocytes in vitro, thus enhancing cartilage regeneration in vivo. In conclusion, the present PEEUUN-KGN scaffolds would have application potential for cartilage tissue engineering.


Assuntos
Materiais Biocompatíveis/química , Cartilagem Elástica/química , Polímeros/química , Engenharia Tecidual , Alicerces Teciduais/química , Ureia/química , Animais , Materiais Biocompatíveis/síntese química , Células Cultivadas , Preparações de Ação Retardada , Ésteres/síntese química , Ésteres/química , Éteres/síntese química , Éteres/química , Humanos , Estrutura Molecular , Tamanho da Partícula , Polímeros/síntese química , Porosidade , Coelhos , Propriedades de Superfície , Ureia/análogos & derivados , Uretana/síntese química , Uretana/química
11.
Biomed Mater ; 15(4): 045001, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-32031994

RESUMO

Preparation of efficient polyurethane-type wound dressings with tunable physicomechanical properties and widespread antimicrobial activity is considered in this work. A new type of soybean oil-based polyol with built-in urethane and quaternary ammonium groups is synthesized through a nonisocyanate route using carbonated soybean oil as an environmentally friendly, renewable resource-based raw material. Different formulations from this polyol and castor oil are prepared and converted to the polyurethane wound dressings via a reaction with isophorone diisocyanate. The dressing sample, with good cytocompatibility and efficient antimicrobial activity against various microbial strains, having tensile strength of 5 and 17 MPa at hydrated and dry state, elongation at the break of up to 400%, equilibrium water absorption and a water vapor transmission rate of 50% and 390 g m-2 day-1, is used for in vivo assay on a rat. Evaluation of the optimized dressing for a full-thickness non-sterilized wound has shown excellent progress of wound healing, since the tensile strength of regenerated skin reaches about 80% of normal healthy skin on day 21 after wounding. This has been significantly superior to the tensile strength of the regenerated skin of rats covered with non-antibacterial (∼50%) and cotton gauze (∼40%) dressings as blank and control groups.


Assuntos
Compostos de Amônio/química , Anti-Infecciosos/química , Bandagens , Óleos de Plantas/química , Polímeros/química , Poliuretanos/química , Uretana/química , Cicatrização , Aminas/química , Animais , Antibacterianos , Óleo de Rícino , Elasticidade , Técnicas In Vitro , Teste de Materiais , Pressão , Ratos , Resistência à Tração , Viscosidade , Água
12.
Molecules ; 24(23)2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31783536

RESUMO

Nowadays, polyols are basic chemicals for the synthesis of a large range of polymers, such as polyurethane foams (PUF), which are produced with several other compounds, such as polyisocyanates. During the last decades, the oleo-chemistry has developed several routes from glycerides to polyols for the polyurethanes (PU) industry to replace mainly conventional fossil-based polyols. A large range of biobased polyols can be now obtained by epoxidation of the double bonds and ring-opening (RO) of the subsequent epoxides with different chemical moieties. In preliminary studies, the RO kinetics of an epoxidized model molecule (methyl oleate) with ethanol and acetic acid were investigated. Subsequently, polyols that were derived from unsaturated triglycerides were explored in the frame of e.g., PUF formulations. Different associations were studied with different mono-alcohols derived from epoxidized and ring-opened methyl oleate while using several ring-openers to model such systems and for comparison purposes. Kinetic studies were realized with the pseudo-first-order principle, meaning that hydroxyls are in large excess when compared to the isocyanate groups. The rate of isocyanate consumption was found to be dependent on the moiety located in ß-position of the reactive hydroxyl, following this specific order: tertiary amine >> ether > ester. The tertiary amine in ß-position of the hydroxyl tremendously increases the reactivity toward isocyanate. Consequently, a biobased reactive polyurethane catalyst was synthesized from unsaturated glycerides. These approaches offer new insights regarding the replacement of current catalysts often harmful, pungent, and volatile used in PU and PUF industry, in order to revisit this chemistry.


Assuntos
Compostos de Epóxi/química , Óleos de Plantas/química , Poliuretanos/síntese química , Catálise , Ésteres/química , Etanol/química , Ácidos Graxos/química , Isocianatos/síntese química , Isocianatos/química , Cinética , Espectroscopia de Ressonância Magnética/métodos , Modelos Químicos , Ácidos Oleicos/química , Polímeros/síntese química , Polímeros/química , Poliuretanos/química , Termodinâmica , Uretana/síntese química , Uretana/química
13.
IET Nanobiotechnol ; 13(7): 703-711, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31573539

RESUMO

The forefront horizon of biomedical investigations in recent decades is parcelling-up and delivery of drugs to achieve controlled/targeted release. In this regard, developing green-based delivery systems for a spatiotemporal controlling therapeutic agent have drawn a lot of attention. A facile route based on cyclic carbonate ring-opening reaction has been utilised to synthesise a bio-based polyol-containing urethane bond [polyol-urethane (POU)] as a nanoparticulate drug delivery system of olanzapine in order to enhance its bioavailability. After characterisation, the nanoparticles were also estimated for in vitro release, toxicity, and pharmacokinetic studies. As olanzapine has shown poor bioavailability and permeability in the brain, the sustained release of olanzapine from the designed carriers could enhance pharmacokinetic effectiveness. POU in the aqueous solution formed micelles with a hydrophobic core and embedded olanzapine under the influence of its hydrophobic nature. Drug release from the nanoparticles (90 ± 0.43 nm in diameter) indicated a specific pattern with initial burst release, and then a sustained release behaviour (82 ± 3% after 168 h), by the Higuchi-based release mechanism. Pharmacokinetics assessments of POU-olanzapine nanoparticles were carried in male Wistar rats through intravenous administration. The obtained results paved a way to introduce the POU as an efficient platform to enhance the bioavailability of olanzapine in therapeutic methods.


Assuntos
Portadores de Fármacos/farmacocinética , Nanopartículas/química , Nanopartículas/metabolismo , Olanzapina/farmacocinética , Óleo de Girassol/química , Animais , Disponibilidade Biológica , Carbonatos/química , Catálise , Técnicas de Química Sintética , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Masculino , Teste de Materiais , Camundongos , Células NIH 3T3 , Olanzapina/administração & dosagem , Polímeros/química , Ratos , Uretana/química
14.
Biomater Sci ; 7(11): 4547-4557, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31463512

RESUMO

Immunomodulatory biomaterials have emerged as a promising approach to engineer wound healing. To achieve this task, the bioactivity of the biomaterials and an easy application are two key desirable characteristics. This work reports an injectable gel system containing immune cells primed for wound healing. By combining the self-assembly of type I collagen, cross-linked with trifunctional oligourethanes, and silica particle entrapment, the structured collagen network acts as a delivery vehicle for macrophages. This structured collagen network primes the macrophages for an anti-inflammatory response. Rheological measurements suggest that the mixture of liquid precursors can be safely stored at low temperatures and low pH (4 °C, pH 3) for at least one month. After pH neutralization and injection, gels with a storage modulus of 50-80 Pa are obtained in five minutes. Several immunocytochemistry and ELISA tests strongly suggest that mouse and human macrophages are stimulated by the material to up-regulate the production of anti-inflammatory cytokines, while down-regulating the production of pro-inflammatory cytokines. The injection of gel in an ex vivo inflammation model of intervertebral discs demonstrated that it is possible to transit from a pro-inflammatory to an anti-inflammatory microenvironment. Altogether, the results suggest that this gel can polarize the macrophage response and promote a surrounding anti-inflammatory microenvironment ready for injection for wound healing applications.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Colágeno/farmacologia , Fatores Imunológicos/farmacologia , Macrófagos/efeitos dos fármacos , Dióxido de Silício/química , Uretana/química , Animais , Anti-Inflamatórios não Esteroides/química , Colágeno/química , Sistemas de Liberação de Medicamentos , Géis/química , Fatores Imunológicos/química , Inflamação/tratamento farmacológico , Inflamação/patologia , Camundongos , Células RAW 264.7 , Cicatrização/efeitos dos fármacos
15.
Biomed Mater ; 14(5): 055001, 2019 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-31207592

RESUMO

Trachea stents are widely used to treat stenosis arising from various trachea injuries. However, they are associated with inflammation, re-stenosis, and tracheal obstruction. Seeking to overcome these problems, the development of an artificial trachea using tissue engineering has been explored. However, the artificial trachea did not mimic the natural rigidity and flexibility of the trachea and provide the micro-environment necessary for re-epithelialization. In this study, we developed a thermoplastic polyurethane (TPU) trachea scaffold that possesses a restoration characteristic, using flexible 3D printed patterns, and an improved cell attachment performance, utilizing electrospun fibers. With the aim of enhancing flexibility, we compared two geometric tubes, one with a straight pattern (SP) and the other with a wave pattern (WP). Simulation results showed that the WP scaffold was more flexible than the SP scaffold. A tensile expansion and torsion experiment demonstrated lower tensile strength and elastic modulus, and higher elongation ratio and rotation angle of the WP scaffold. Addition of the electrospun layers increased the tensile strength and elastic modulus and decreased the elongation ratio and rotation angle of both the SP and WP scaffolds. The same trend was observed regardless of electrospinning. However, polycaprolactone (PCL)-based scaffolds displayed lower elongation ratio and rotation angle in simulations and experiments. Although the cell attachment capacity of TPU-based electrospun WP scaffolds was less than 10% that of PCL-based scaffolds, the former showed good initial cell attachment performance and their cell numbers increased by more than three times within a week. The improved biomechanical performance and cell affinity of the TPU trachea scaffold could be exploited in patient-customized grafts for trachea reconstruction.


Assuntos
Constrição Patológica/terapia , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Traqueia/fisiopatologia , Fenômenos Biomecânicos , Adesão Celular , Proliferação de Células , Simulação por Computador , Elasticidade , Humanos , Inflamação , Células-Tronco Mesenquimais/citologia , Plásticos , Poliésteres/química , Impressão Tridimensional , Desenho de Prótese , Stents , Estresse Mecânico , Resistência à Tração , Traqueia/patologia , Uretana/química
16.
ChemMedChem ; 14(12): 1196-1203, 2019 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-31020782

RESUMO

Exploiting the redox sensitivity of disulfide bonds is a prevalent strategy in targeted prodrug designs. In contrast to aliphatic disulfides, p-thiobenzyl-based disulfides have rarely been used for prodrug designs, given their intrinsic instability caused by the low pKa of aromatic thiols. Here, we examined the interplay between steric hindrance and the low-pKa effect on thiol-disulfide exchange reactions and uncovered a new thiol-disulfide exchange process for the self-immolation of p-thiobenzyl-based disulfides. We observed a central leaving group shifting effect in the α,α-dimethyl-substituted p-dithiobenzyl urethane linkers (DMTB linkers), which leads to increased disulfide stability by more than two orders of magnitude, an extent that is significantly greater than that observed with typical aliphatic disulfides. In particular, the DMTB linkers display not only high stability, but also rapid self-immolation kinetics due to the low pKa of the aromatic thiol, which can be used as a general and robust linkage between targeting reagents and cytotoxic drugs for targeted prodrug designs. The unique and promising stability characteristics of the present DMTB linker will likely inspire the development of novel targeted prodrugs to achieve traceless release of drugs into cells.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Dissulfetos/química , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Pró-Fármacos/química , Uretana/química , Antibióticos Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Doxorrubicina/química , Desenho de Fármacos , Humanos , Estrutura Molecular , Relação Estrutura-Atividade
17.
Biomed Mater ; 14(3): 035001, 2019 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-30699400

RESUMO

INTRODUCTION: Bone tissue regeneration requires a three-dimensional biological setting. An ideal scaffold should enable cell proliferation and differentiation by mimicking structure and mechanical properties of the compromised defect as well as carrying growth factors. Two-photon polymerization (2PP) allows the preparation of 3D structures with a micrometric resolution. METHODS: In this study, 2PP was applied to design scaffolds made from biocompatible methacrylated D,L-lactide-co-ε-caprolactone copolymers (LC) with a controlled porous architecture. Proliferation and differentiation of bone marrow mesenchymal stromal cells on LC was analyzed and compared to a standard inorganic urethane-dimethacrylate (UDMA) matrix. To functionalize LC and UDMA surfaces we analyzed a biomimetic, layer-by-layer coating, which could be modified in stiffness and integration of bone morphogenetic protein 2 (BMP2) and evaluated its effect on osteogenic differentiation. RESULTS: On LC surfaces, BMSC demonstrated an optimal proliferation within pore sizes of 60-100 µm and showed a continuous expression of Vimentin. On the polyelectrolyte multilayer coating a significant increase in BMSC proliferation and differentiation as marked by Osteonectin expression was achieved using stiffness modification and BMP2 functionalization. CONCLUSION: Combining 3D-Design with biofunctionalization, LC offers a promising approach for future regenerative applications in osteogenic differentiation of BMSCs.


Assuntos
Proteína Morfogenética Óssea 2/química , Regeneração Óssea , Células-Tronco Mesenquimais/citologia , Poliésteres/química , Engenharia Tecidual/métodos , Osso e Ossos , Técnicas de Cultura de Células , Diferenciação Celular , Proliferação de Células , Eletrólitos , Escherichia coli , Humanos , Osteogênese , Fótons , Polimerização , Porosidade , Medicina Regenerativa , Estresse Mecânico , Alicerces Teciduais , Uretana/química
18.
J Biomater Appl ; 33(6): 854-865, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30458659

RESUMO

Natural biopolymers have many attractive medical applications; however, complications due to fibrosis caused a reduction in diffusion and dispersal of nutrients and waste products. Consequently, severe immunocompatibility problems and poor mechanical and degradation properties in synthetic polymers ensue. Hence, the present study investigates a novel hydrogel material synthesized from caprolactone, ethylene glycol, ethylenediamine, polyethylene glycol, ammonium persulfate, and tetramethylethylenediamine via chemo-enzymatic route. Spectroscopic analyses indicated the formation of polyurea and polyhydroxyurethane as the primary building block of the hydrogel starting material. Biocompatibility studies showed positive observation in biosafety test using direct contact cytotoxicity assay in addition to active cellular growth on the hydrogel scaffold based on fluorescence observation. The synthesized hydrogel also exhibited (self)fluorescence properties under specific wavelength excitation. Hence, synthesized hydrogel could be a potential candidate for medical imaging as well as tissue engineering applications as a tissue expander, coating material, biosensor, and drug delivery system.


Assuntos
Materiais Biocompatíveis/química , Hidrogéis/química , Células-Tronco Mesenquimais/citologia , Polímeros/química , Uretana/análogos & derivados , Animais , Materiais Biocompatíveis/síntese química , Células Cultivadas , Hidrogéis/síntese química , Teste de Materiais , Polímeros/síntese química , Coelhos , Engenharia Tecidual , Alicerces Teciduais/química , Uretana/síntese química , Uretana/química
19.
Sci Total Environ ; 646: 606-617, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30059921

RESUMO

Petroleum refinery wastewater (PRW) treatments based on biofilm membrane bioreactor (BF-MBR) technology is an ideal approach and biofilm supporting material is a critical factor. In this study, BF-MBR with nano-attapulgite clay compounded hydrophilic urethane foams (AT/HUFs) as a biofilm support was used to treat PRW with a hydraulic retention time of 5 h. The removal rate of 500 mg/L chemical oxygen demand (COD), 15 mg/L NH4+ and 180 NTU of turbidity were 99.73%, 97.48% and 99.99%, which were 23%, 20%, and 6% higher than in the control bioreactor, respectively. These results were comparatively higher than that observed for the sequencing batch reactor (SBR). The death rate of the Spirodela polyrrhiza (L.) irrigated with BF-MBR-treated water was 4.44%, which was similar to that of the plants irrigated with tap water (3.33%) and SBR-treated water (5.56%), but significantly lower than that irrigated with raw water (84.44%). The counts demonstrated by qPCR for total bacteria, denitrifiers, nitrite oxidizing bacteria, ammonia oxidizing bacteria, and ammonia-oxidizing archaea were also higher in BF-MBR than those obtained by SBR. Moreover, the results of 16 s rRNA sequencing have demonstrated that the wastewater remediation microbes were enriched in AT/HUFs, e.g., Acidovorax can degrade polycyclic aromatic hydrocarbons, and Sulfuritalea is an efficient nitrite degrader. In summary, BF-MBR using AT/HUF as a biofilm support improves microbiome of the actived sludge and is reliable for oil-refinery wastewater treatment.


Assuntos
Reatores Biológicos/microbiologia , Compostos de Magnésio/química , Compostos de Silício/química , Uretana/química , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/química , Biofilmes/crescimento & desenvolvimento , Argila/química , Membranas Artificiais , Águas Residuárias/microbiologia , Purificação da Água
20.
J Biomater Appl ; 33(7): 903-914, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30526211

RESUMO

The stability and bioactivity of biologic implants rely mainly on the control of the crosslinking process of collagen. However, the most common methods have no control on the crosslinking degree producing it excessively. This study outlines the role of crosslinking of collagen-based implants with oligourethane on the host response following reconstruction of a rat full-thickness abdominal wall defect. We decellularized and crosslinked bovine pericardial tissue to achieve two crosslinking degrees. For the decellularized implants, named as non-crosslinked (N-CL), the collagen-amines were 0.42 ± 0.02 mmol/mg. Crosslinking by the oligourethane reduced the primary amine concentration to 0.28 ± 0.01 and 0.19 ± 0.01 mmol/mg; these values were classified as low (∼30%, L-CL) and medium crosslinking (∼50%, M-CL), respectively. By imaging the implants using second harmonic generation microscopy, we observed undulated bundles of collagen fibers organized in multi-directed layers localized in N-CL and L-CL samples. Post-implantation, a negligible change in the organization of collagen fibers in the crosslinked implants was observed, suggesting that the in vivo biodegradation was delayed. An enlargement of the implant area was also observed, without rupture, in all three (N-CL, L-CL, M-CL) materials, whereas adhesion to the omentum, but not to the bowel, was observed. The number of blood vessels after 90-day implantation in N-CL and L-CL was 13 ± 1 and 12 ± 1 per field, respectively, while the number significantly decreased to 2 ± 1 in M-CL. The results suggest that the controlled degree of crosslinking in oligourethane-modified biologic implants can be used as a strategy to balance biodegradation and remodeling in surgical repair of soft tissues.


Assuntos
Parede Abdominal/cirurgia , Materiais Biocompatíveis/química , Colágeno/química , Reagentes de Ligações Cruzadas/química , Pericárdio/química , Uretana/química , Parede Abdominal/patologia , Animais , Bioprótese , Bovinos , Masculino , Pericárdio/transplante , Pericárdio/ultraestrutura , Ratos , Ratos Wistar , Procedimentos de Cirurgia Plástica , Resistência à Tração
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