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1.
Biomater Adv ; 151: 213473, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37245344

RESUMO

Zein has enormous potential for application in biomedical field due to biodegradation and biocompatibility, we have recently prepared zein gel as a possible 3D printing ink. Our previous studies found that the pore structure in zein material can reduce early inflammation, promote the polarization of macrophages toward the M2 phenotype, and accelerate nerve regeneration. To further explore the role of zein in nerve repair, we used 4D printing technique to create nerve conduits with zein protein gel, and designed 2 types of tri-segment conduits with different degradation rates. Structural parts printed in support baths with higher water content show faster degradation rates than those printed in support baths with lower water content. The conduits that degraded quickly at both ends and slowly in the middle (CB75-CB40-CB75) and the conduits that degraded slowly at both ends and quickly in the middle (CB40-CB75-CB40) were 4D printed, respectively. Animal experiments suggest that the CB75-CB40-CB75 conduit is better for nerve repair, which may be because its degradation pattern can match to the pattern of nerve regeneration better. Our new strategy through 4D printing indicated that fine modulation in conduit degradation can affect efficacy of nerve repair significantly.


Assuntos
Tecido Nervoso , Zeína , Ratos , Animais , Ratos Sprague-Dawley , Zeína/química , Tinta , Nervo Isquiático/cirurgia , Nervo Isquiático/fisiologia
2.
Biomed Mater ; 18(2)2023 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-36649654

RESUMO

The identification of degraded products of implanted scaffolds is desirable to avoid regulatory concerns.In vivoidentification of products produced by the degradation of natural protein-based scaffolds is complex and demands the establishment of a routine analytical method. In this study, we developed a method for the identification of peptides produced by the degradation of zein bothin vitroandin vivousing high performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). Forin vitroexperiments, zein was degraded enzymatically and analyzed produced peptides.In vitrostudy showed cytocompatibility of peptides present in the hydrolysate of zein with no induction of apoptosis and cell senescence. Forin vivoexperiment, zein gels were prepared and subcutaneously implanted in rats. Peptides produced by the degradation of zein were identified and few were selected as targeted (unique peptides) and two peptides were synthesized as the reference sequence of these peptides. Further, peptide analysis using HPLC-MS/MS of different organs was performed after 2 and 8 weeks of implantation of zein gel in rats. It was found that zein-originated peptides were accumulated in different organs. QQHIIGGALF or peptides with same fractions were identified as unique peptides. These peptides were also found in control rats with regular rat feed, which means the degradation of implanted zein biomaterial produced food related peptides of non-toxic nature. Furthermore, hemotoxylin and eosin (H&E) staining exhibited normal features. Overall, zein degraded products showed cytocompatibility and did not induce organ toxicity, and QQHIIGGALF can act as a standard peptide for tracing and determining zein degradation. The study also provides the feasibility of complex analysis on identification and quantification of degradation products of protein-based scaffolds.


Assuntos
Espectrometria de Massas em Tandem , Zeína , Ratos , Animais , Cromatografia Líquida de Alta Pressão/métodos , Zeína/química , Peptídeos/química , Proteínas
3.
Biomater Adv ; 145: 213225, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36527960

RESUMO

Zein is a biocompatible and biodegradable corn protein with promising properties for biomedical applications. It is hydrophobic with the ability to self-assemble in an aqueous medium. It can also form a gel in hydroalcoholic solvents at higher concentrations. Few studies have investigated the biomedical significance of zein gels. Herein, we exploited the injectability and water-responsive increase in stiffness of zein gel to achieve hemostasis by physical blockage of the wound and clot formation. The release of components from the gel further aided blood clotting and gave a higher clot strength than a natural clot, which can prevent rebleeding. Rabbit aortic injury and swine femoral artery injury models were used to evaluate the hemostatic efficacy of the zein gel. Zein gel was effective in both hemostatic models without applying external compression due to an in situ increase in stiffness, while the control (Celox™ Gauze) required external compression at the wound site. The zein gel was easily removed after hemostasis due to hydrophobic self-assembly. Overall, zein gel is proposed as an effective hemostatic product for any wound shape owing to its good shape adaptability and rapid in situ blood-responsive stiffness increase.


Assuntos
Hemostáticos , Zeína , Suínos , Animais , Coelhos , Hemostáticos/farmacologia , Zeína/química , Hemostasia , Géis , Bandagens
4.
Bioact Mater ; 23: 343-352, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36474653

RESUMO

Four-dimensional (4D) printing is a promising technology that provides solutions for compelling needs in various fields. Most of the reported 4D printed systems are based on the temporal shape transformation of printed subjects. Induction of temporal heterogenicity in functions in addition to shape may extend the scope of 4D printing. Herein, we report a 4D printing approach using plant protein (zein) gel inspired by the amyloid fibrils formation mechanism. The printing of zein gel in a specialized layered-Carbopol supporting bath with different water concentrations in an ethanol-water mixture modulates hydrophobic and hydrogen bonding that causes temporal changes in functions. The part of the construct printed in a supporting bath with higher water content exhibits higher drug loading, faster drug release and degradation than those printed in the supporting bath with lower water content. Tri-segment conduit and butterfly-shaped construct with two asymmetrical wings are printed using this system to evaluate biomedical function as nerve conduit and drug delivery system. 4D printed conduits are also effective as a drug-eluting urethral stent in the porcine model. Overall, this study extends the concept of 4D printing beyond shape transformation and presents an approach of fabricating specialized baths for 4D printing that can also be extended to other materials to obtain 4D printed medical devices with translational potential.

5.
ACS Appl Mater Interfaces ; 14(47): 52670-52683, 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36379044

RESUMO

Photothermal therapy (PTT) is regarded as one of the potential techniques to replace surgery in the treatment of tumors. Polyaniline (PANI) shows better biocompatibility than inorganic reagents, which has been widely used in tumor photoacoustic (PA) imaging and PTT. However, the poor water solubility and nonspecific aggregation of PANI nanoparticles severely restricted their biomedical application. In addition, it is difficult to control the photothermal effect just on cancer cells. Herein, we develop tumor pH-responsive PANI-Gel/Cu assemblies, which can achieve targeted and precise ablation of tumors. Due to the high hydrophilicity of gelatin, the PANI-Gel/Cu assemblies show excellent dispersion in physiological solutions and long-term stability. By taking advantage of the self-doping effect between the carboxyl groups in gelatin and the imine part of the PANI skeleton, the photothermal characteristics of PANI-Gel/Cu assemblies can be promoted effectively by the acid tumor microenvironment, and the PA imaging of PANI-Gel/Cu assemblies can also be activated by tumor pH. Consequently, both the PTT enhancement and PA signal amplification can be triggered under a tumor microenvironment, and PANI-Gel/Cu assemblies can be targeted to cancer cells with the RGD sequences in their gelatin skeleton. In vivo imaging-guided PTT to A549 cancer shows precise treatment with little harm to normal cells, and PANI-Gel/Cu assemblies can disassemble into tiny particles (<15 nm) under laser irradiation. This work overcomes the intrinsic limitation of PANI materials, i.e., poor water solubility and nonspecific aggregation, meanwhile providing a pH-active PANI-based platform for precise and effective ablation of cancer.


Assuntos
Hipertermia Induzida , Nanopartículas , Neoplasias , Técnicas Fotoacústicas , Humanos , Fototerapia/métodos , Hipertermia Induzida/métodos , Terapia Fototérmica , Técnicas Fotoacústicas/métodos , Gelatina , Água , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Concentração de Íons de Hidrogênio , Linhagem Celular Tumoral , Microambiente Tumoral
6.
World J Clin Cases ; 10(22): 7642-7652, 2022 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-36158479

RESUMO

Imaging techniques are useful tools in the diagnosis and treatment of pancreaticobiliary maljunction (PBM). PBM is a precancerous lesion often relative to the disease of the pancreas and biliary tract, for example, cholecystolithiasis, protein plugs, and pancreatitis. For patients with PBM, early diagnosis and timely treatment are highly important, which is largely dependent on imaging techniques. The continuous development of imaging techniques, including endoscopic retrograde cholangiopancreatography, magnetic resonance cholangiopancreatography, computed tomography, ultrasound, and intraoperative cholangiography, has provided appropriate diagnostic and therapeutic tools for PBM. Imaging techniques, including non-invasive and invasive, have distinct advantages and disadvantages. The purpose of this paper is to review the application of various imaging techniques in the diagnosis and treatment of PBM.

7.
Int J Pharm ; 627: 122206, 2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-36126824

RESUMO

Recently, biomedical applications of organogels have been increasing; however, there is a demand for bio-based polymers. Here, we report self-assembled zein organogels in N-methyl pyrrolidone (NMP), Dimethyl sulfoxide (DMSO), and glycerol formal (GF). The gel formation was driven by the solvent's polarity and the hydrogen bonding component of Hansen Solubility Parameters was important in promoting gelation. Gels exhibited shear-thinning and thixotropic properties. Furthermore, water-induced self-assembly of zein allows mechanically robust in situ implant formation by solvent exchange. Ciprofloxacin was incorporated as a model drug and sustained release depending upon the solvent exchange rate was observed. In situ implants in agarose gel retained antibacterial efficacy against S. aureus for more than 14 days. Zein-based organogels were further applied as 3D printing ink and it was found that zein gel in DMSO had superior printability than gels prepared in NMP and GF. Using three solvents to prepare organogels can enable the encapsulation of various drugs and facilitate the preparation of composite gels with other biocompatible polymers. These organogel systems can further be used for developing 3D printed drug delivery systems or scaffolds for tissue engineering.


Assuntos
Zeína , Dimetil Sulfóxido , Tinta , Preparações de Ação Retardada , Staphylococcus aureus , Sefarose , Excipientes , Géis , Solventes , Polímeros , Água , Impressão Tridimensional , Antibacterianos , Ciprofloxacina
8.
Int J Biol Macromol ; 205: 110-117, 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35149100

RESUMO

Trauma-related excessive bleeding is one of the leading causes of death. Chitosan (CS) sponges have unique advantages in the treatment of massive bleeding, but their application is limited by poor stability and toxic crosslinking agent. In this work, chitosan/polyvinylpyrrolidone/zein (CS/PVP/Zein) sponges with macroporous structure were prepared, which exhibited rapid water absorption capacity and water-triggered expanding property with low cytotoxicity and low hemolysis ratio. In vitro blood coagulation experiments showed that CS/PVP/Zein sponges could clot blood significantly faster than commercial surgical gauze. Further investigation of the hemostatic mechanism suggested that the CS/PVP/Zein sponges could accelerate coagulation by promoting attachment of erythrocytes, activation of platelets, and rapid plasma protein absorption. Prepared sponges were also found effective in the rat femoral artery transection model to control bleeding. Overall, the CS/PVP/Zein sponges exhibited the potential to control trauma-related hemorrhage.


Assuntos
Quitosana , Hemostáticos , Zeína , Animais , Quitosana/química , Quitosana/farmacologia , Hemostasia , Hemostáticos/química , Povidona/farmacologia , Ratos , Zeína/farmacologia
9.
Acta Biomater ; 140: 289-301, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34843952

RESUMO

Zein is a biodegradable material with great potential in biomedical applications. However, as a plant-derived protein material, body's immune response is the key factor to determine its clinical performance. Herein, for the first time, the zein-induced immune response is evaluated systemically and locally, comparing with typical materials including alginate (ALG), poly(lactic-co-glycolic) acid (PLGA) and polystyrene (PS). Zein triggers an early inflammatory response consistent with the non-degradable PS, but this response decreases to the same level of the biosafe ALG and PLGA with zein degradation. Changing sphere sizes, pore structure and encapsulating dexamethasone can effectively modulate the zein-induced immune response, especially the pore structure which also inhibits neutrophil recruitment and promotes macrophages polarizing towards M2 phenotype. Thus, porous zein conduits with high and low porosity are further fabricated for the 15 mm sciatic nerve defect repair in rats. The conduits with high porosity induce more M2 macrophages to accelerate nerve regeneration with shorter degradation period and better nerve repair efficacy. These findings suggest that the pore structure in zein materials can alleviate the zein-induced early inflammation and promote M2 macrophage polarization to accelerate nerve regeneration. STATEMENT OF SIGNIFICANCE: Zein is a biodegradable material with great potential in biomedical applications. However, as a plant protein, its possible immune response in vivo is always the key issue. Until now, the systemic study on the immune responses of zein in vivo is still very limited, especially as an implant. Herein, for the first time, the zein-induced immune response was evaluated systemically and locally, comparing with typical biomaterials including alginate, poly(lactic-co-glycolic) acid and polystyrene. Changing sphere sizes, pore structure and encapsulating dexamethasone could effectively modulate the zein-induced immune response, especially the pore structure which also inhibited neutrophil recruitment and promoted macrophages polarizing towards M2 phenotype. Furthermore, the pore structure in zein nerve conduits was proved to alleviate the early inflammation and promote M2 macrophage polarization to accelerate nerve regeneration.


Assuntos
Zeína , Animais , Imunidade , Regeneração Nervosa/fisiologia , Ratos , Ratos Sprague-Dawley , Nervo Isquiático/fisiologia , Zeína/química , Zeína/farmacologia
10.
Biomed Mater ; 16(6)2021 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-34517347

RESUMO

As a novel bone substitute material, zein-based scaffolds (ZS) should have suitable mechanical properties and porosity. ZS has shown good compressive properties matching cancellous bone, but there is still a demand to improve its mechanical properties, especially tensile and bending properties without adding plasticizers. The present study explored two simple and environment-friendly factors for this purpose: fiber reinforcement and quenching. Addition of electrospun zein fibers enhanced all mechanical properties significantly including compressive, tensile, and bending moduli; compressive and bending strengths of ZS with both higher (70-80%) and lower (50-60%) porosities, no matter whether heating treated or not treated. Especially, all these parameters were further enhanced significantly by addition of heating treated fibers. AFM provided evidence that high temperature modification could significantly alter the micro-elastic properties of zein electrospun fibers, i.e., increased stiffness of fibers. Quenching treatment also enhanced compressive, tensile, and bending strengths significantly. Finally, quenching treated ZS were implanted into critical-sized bone defects (15 mm) of the rabbit model to compare the repair efficacy with a commercial ß-tricalcium phosphate product. The results demonstrated that there were no remarkable differences in bone reconstructions between these two materials.


Assuntos
Substitutos Ósseos/química , Alicerces Teciduais/química , Zeína/química , Animais , Substitutos Ósseos/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Técnicas Eletroquímicas , Teste de Materiais , Camundongos , Porosidade , Coelhos , Rádio (Anatomia)/efeitos dos fármacos , Rádio (Anatomia)/patologia , Engenharia Tecidual , Zeína/farmacologia
11.
Mater Sci Eng C Mater Biol Appl ; 122: 111900, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33641903

RESUMO

In order to prevent thrombosis, reduce intima hyperplasia, and to maintain long-term patency after implantation of an artificial blood vessel, the formation of intact endothelial cells layer on an inner surface of graft is desirable. The present study aimed to improve endothelial cell adhesion by regulating the morphology of the inner surface of artificial blood vessels. Zein fibre membranes with three fibre diameters (small, ~100 nm; medium, ~500 nm; and large, ~1000 nm) were constructed by electrospinning. A flow chamber device was designed to simulate the blood flow environment. The morphology and adhesion of human umbilical vein fusion cells (EA.hy926) on the surface of the fibre membranes were studied under a shear stress of approximately 15 dynes/cm2. The results showed that oriented electrospun zein fibre surfaces with both medium- and large-diameter fibres can regulate the morphology of endothelial cells (EA.hy926), which are aligned by the fibre direction. The three fibre membranes improved the adhesion of endothelial cells significantly compared to that on the flat membrane. When the fibre direction was fixed parallel to the fluid direction, the medium-diameter oriented-fibre membrane could significantly improve the ability endothelial cells to resist shear stress, and there was a significant difference at 1, 2 and 4 h time points compared with the shear stress resistance on the small-diameter and large-diameter oriented-fibre membranes. When the fibre direction was perpendicular to the fluid direction, again the medium-diameter oriented-fibre membrane improved the ability of endothelial cells to resist shear stress significantly at 1 and 2 h time points. It was concluded that by changing the diameter and arrangement of electrospun fibres, cell morphology control and shear stress resistance can be achieved.


Assuntos
Circulação Sanguínea , Nanoestruturas , Zeína , Adesão Celular , Células Endoteliais , Humanos , Estresse Mecânico
12.
J Mech Behav Biomed Mater ; 113: 104114, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33045517

RESUMO

The poor elasticity of wound dressings often leads to wound healing failure due to rupture and fall off. In this study, the composite films of zein and hydrogel poly (acrylic acid) were developed in order to obtain stretchable wound dressing for skin burn repair. The mechanical test revealed that the maximum elongation of break of composite films could reach 349.76% when the mass ratio of zein to poly (acrylic acid) was 1.5. SEM and FTIR analysis demonstrated the good elasticity of composite films might be due to the formation of a dense structure and the strong interaction between zein and poly (acrylic acid). Interestingly, the composite films exhibited great adhesiveness to human finger skin and stretchable ability under strenuous joint exercise. CCK-8 assay and fluorescence staining showed that the composite films and their extract had good cytocompatibility on human foreskin fibroblasts (L929) cells. The in vivo experiment on rat's skin burning model indicated that the composite films could promote wound healing and collagen synthesis by comparison with commercial gauze. It could be concluded that the stretchable composite films of zein and hydrogel poly (acrylic acid) had the potential as the wound dressing.


Assuntos
Queimaduras , Cicatrização , Animais , Bandagens , Queimaduras/terapia , Hidrogéis , Ratos , Pele
13.
Mater Sci Eng C Mater Biol Appl ; 111: 110766, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32279795

RESUMO

Conduit scaffolds have potential applications in tissue engineering as nerve conduits, urological stent and blood vessel graft. Zein is a well-reported biopolymer in tissue engineering and drug delivery systems. Herein, we prepared ciprofloxacin loaded zein conduits using a facile rolling method. Zein conduits (ZCs) were evaluated for physical structure, porosity, bending stiffness, degradation, drug release, in vitro and in vivo antibacterial efficacy and cells toxicity. ZCs showed porous structure with porosity > 60 % and good mechanical strength with bending stiffness of 28.54 N.mm2. Slow enzymatic degradation (87 % in 30 days) was also observed for ZCs. Slow release of ciprofloxacin up to 42 days was observed that could assure prevention of post-implantation infection. In vitro and in vivo antibacterial study verified the short-time and long-time antibacterial efficacy of zein conduits on Gram-positive and Gram-negative bacteria. Live/dead measurement and CCK-8 assay on L929 cells demonstrated good cell compatibility for all zein conduits (>90 % cell viability and cells proliferation in 3 days). Overall, the rolling method could be exploited for preparation of ciprofloxacin loaded zein conduits, which had the potential for tissue engineering applications.


Assuntos
Antibacterianos/química , Ciprofloxacina/química , Zeína/química , Animais , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Ciprofloxacina/metabolismo , Ciprofloxacina/farmacologia , Ciprofloxacina/uso terapêutico , Força Compressiva , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Masculino , Camundongos , Porosidade , Ratos , Ratos Sprague-Dawley , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/veterinária , Cicatrização/efeitos dos fármacos
14.
Int J Pharm ; 579: 119185, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32112929

RESUMO

In this study, gastro-retentive porous floating tablets of captopril based on zein are reported using l-menthol as a porogen. Tablets were prepared by the direct compression method. Removing of l-menthol through sublimation process generated pores in tablets, which decreased the density to promote floating over gastric fluid. Prepared tablets showed no floating lag time and prolong total floating time (>24 h). Drug release was found dependent upon porosity of tablets, an increase in porosity of tablets resulted in increased drug release, so it can be tuned by varying concentration of l-menthol. In addition to floating and sustained release properties, porous tablets showed robust mechanical behavior in wet conditions, which can enable them to withstand real gastric environment stress. In vivo studies using New Zealand rabbits also confirmed the prolonged gastric retention (24 h) and plasma drug concentration-time profile showed sustained release of captopril with higher Tmax and MRT as compared to marketed immediate-release tablets. Overall, it was concluded that effective gastric retention can be achieved using porous zein tablets using l-menthol as a porogen.


Assuntos
Captopril/química , Captopril/farmacocinética , Mucosa Gástrica/metabolismo , Comprimidos/química , Zeína/química , Animais , Captopril/sangue , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Liberação Controlada de Fármacos/efeitos dos fármacos , Mentol/química , Porosidade , Coelhos
15.
J Biomed Mater Res B Appl Biomater ; 108(1): 128-142, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30912286

RESUMO

Endowing the conduit with conductivity has been an effective way to stimulate nerve growth and functional recovery. Here, conducting polyaniline (PANi) was used to construct a conductive guidance by coating on the surface of microtubes inserted in a three-dimensional zein nerve conduit to study the repairing efficacy on peripheral nerve injury. PANi nanoparticles with a size of 20-30 nm were synthesized and coated on the surface of microtubes through layer-by-layer deposition. Then, conduits including microtubes with and without PANi coating were implanted into rats to bridge a 10-mm sciatic nerve defect and autograft as the control group. After 2 months, the conduit with PANicoating improved the recovery of proximal compound muscle action potential significantly in the regenerated nerve compared to the conduit without PANi coating, which was not inferior to the autograft group. However, the repairing efficacy was changed reversely at the fourth month postimplantation. PANi coating fragmented to form debris within or around the regenerated nerves while microtubes seem to degrade completely as observed by H&E staining. In vitro degradation experiment confirmed this process. The PANi nanoparticles could induce cytotoxicity and reactive oxygen species (ROS) generation of both NIH 3T3 cells and macrophage cell line RAW 264.7. These in vitro and in vivo results implied that the nondegradable PANi may occupy the regeneration space and stimulate the inflammatory response in later implantation in vivo. While there was no such risk if the PANi coating keeps in an intact film. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:128-142, 2020.


Assuntos
Compostos de Anilina/farmacologia , Materiais Revestidos Biocompatíveis/farmacologia , Regeneração Nervosa , Traumatismos dos Nervos Periféricos/terapia , Nervo Isquiático/fisiologia , Compostos de Anilina/química , Animais , Materiais Revestidos Biocompatíveis/química , Masculino , Camundongos , Células NIH 3T3 , Células PC12 , Traumatismos dos Nervos Periféricos/metabolismo , Traumatismos dos Nervos Periféricos/patologia , Células RAW 264.7 , Ratos , Ratos Sprague-Dawley , Nervo Isquiático/lesões , Nervo Isquiático/patologia
16.
J Mech Behav Biomed Mater ; 103: 103533, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31747624

RESUMO

To overcome the mechanical drawback of bioink, we proposed a supporter model to enhance the mechanical strength of bioprinted 3D constructs, in which a unit-assembly idea was involved. Based on Computed Tomography images of critical-sized rabbit bone defect, the 3D re-construction was accomplished by a sequenced process using Mimics 17.0, BioCAM and BioCAD software. 3D constructs were bioprinted using polycaprolactone (PCL) ink for the outer supporter under extrusion mode, and cell-laden tricalcium phosphate (TCP)/alginate bioink for the inner filler under air pressure dispensing mode. The relationship of viscosity of bioinks, 3D bioprinting pressure, TCP/alginate ratio and cell survival were investigated by the shear viscosities analysis, live/dead cell test and cell-counting kit 8 measurement. The viscosity of bioinks at 1.0 s-1-shear rate could be adjusted within the range of 1.75 ±â€¯0.29 Pa·s to 155.65 ±â€¯10.86 Pa·s by changing alginate concentration, corresponding to 10 kPa-130 kPa of printing pressure. This design with PCL supporter could significantly enhance the compressive strength and compressive modulus of standardized 3D mechanical testing specimens up to 2.15 ±â€¯0.14 MPa to 2.58 ±â€¯0.09 MPa, and 42.83 ±â€¯4.75 MPa to 53.12 ±â€¯1.19 MPa, respectively. Cells could maintain the high viability (over 80%) under the given printing pressure but cell viability declined with the increase of TCP content. Cell survival after experiencing 7 days of cell culture could be achieved when the ratio of TCP/alginate was 1 : 4. All data supported the feasibility of the supporter and unit-assembly model to enhance mechanical properties of bioprinted 3D constructs.


Assuntos
Alginatos , Bioimpressão , Animais , Fosfatos de Cálcio , Sobrevivência Celular , Impressão Tridimensional , Coelhos , Alicerces Teciduais
17.
Eur J Pharm Sci ; 132: 163-173, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-30695689

RESUMO

The present study aimed to investigate the potential of zein (a protein obtained from corn) for development of gastroretentive floating tablets for the first time. A compression coated tablet design with outer floating layer and inner drug containing layer was followed to achieve floating over gastric fluid with sustained release of drug. Captopril was used as a model drug for this purpose. Eight formulations were developed and the influence of different components on drug release and floating behavior was evaluated. The drug in coating layer was found to be released at faster rate while sustained release behavior was observed from core layer. In vivo pharmacokinetic studies on rabbits showed significant increase in bioavailability and mean residence time (MRT). Moreover, radiographic study exhibited gastric retention of prepared tablets >12 h. In conclusion, zein can be used for development of gastroretentive floating tablets and by adjusting amount of different formulation factors, desired drug release rate can be achieved.


Assuntos
Captopril/química , Captopril/farmacocinética , Desenho de Fármacos , Mucosa Gástrica/metabolismo , Zeína/química , Administração Oral , Animais , Disponibilidade Biológica , Captopril/administração & dosagem , Liberação Controlada de Fármacos , Feminino , Absorção Gástrica , Coelhos , Solubilidade , Propriedades de Superfície , Comprimidos
18.
Free Radic Res ; 52(11-12): 1424-1431, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30203697

RESUMO

Reactive oxygen species (ROS) caused by ultraviolet A (UVA) can be reduced by treating with antioxidants and photoprotective reagents. Here we reported a real-time chemiluminescence (CL) imaging method which was simple, non-invasive and sensitive to evaluate UVA-induced ROS generation and the efficacy of sunscreens and antioxidants in vivo. The in vitro experiments indicated that l-ascorbic acid, live SPSC01 yeast, and its intracellular metabolites can suppress the intensity of CL signals in the presence of hydrogen peroxide, which proved the good antioxidant ability of them. Meanwhile, we used 8-amino-5-chloro-7-phenylpyrido[3,4-d] pyridazine-1,4(2H,3H) dione (L-012) as a high sensitive CL probe for in vivo imaging of ROS generated by UVA irradiation. The CL intensity was reduced after treated with l-ascorbic acid and SPSC01 yeast intracellular metabolites, consistent with the in vitro results. Additionally, the in vivo protective capability of two azobenzene compounds as sunscreens was confirmed further through the suppression of CL signals of UVA-induced ROS in mouse skin by this method.


Assuntos
Medições Luminescentes , Luminol/análogos & derivados , Imagem Óptica , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/efeitos da radiação , Pele/metabolismo , Pele/efeitos da radiação , Raios Ultravioleta , Animais , Feminino , Luminescência , Luminol/análise , Luminol/química , Camundongos , Camundongos Endogâmicos
19.
J Biomed Mater Res A ; 106(2): 606-613, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28960906

RESUMO

Given the inadequacies of existing clinic tracking strategies, such as isotopic tracer techniques, one of the major thrusts in protein-based tissue engineering substitutes prior to use in clinic is to develop a safe technique that can effectively track their degradation in vivo. Keeping in view the possible application of a natural polymer, zein as a novel bone substitute, with the advantages of good bio-compatibility, bio-degradability and outstanding mechanical properties, we attempted here to construct a HPLC-MS/MS method to track the in vivo degradation of zein porous scaffold. Histological observation and immunohistochemistry analysis using the intramuscular implantation model of rats clearly indicated that zein porous scaffold has certain osteoinductive ability. More importantly, HPLC-MS/MS detected the changes of amino acids levels in plasma and different organs after the implantation of scaffolds. With these findings, it could be concluded that HPLC-MS/MS might be a potential method to track the in vivo degradation of protein-based tissue engineering substitutes. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 606-613, 2018.


Assuntos
Materiais Biocompatíveis/química , Espectrometria de Massas em Tandem/métodos , Zeína/química , Aminoácidos/análise , Animais , Substitutos Ósseos/química , Coristoma/patologia , Cromatografia Líquida de Alta Pressão , Feminino , Masculino , Osteogênese , Implantação de Prótese , Ratos Sprague-Dawley , Padrões de Referência
20.
ACS Biomater Sci Eng ; 4(5): 1880-1890, 2018 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-33445343

RESUMO

Well-dispersed polyaniline (PANi) nanoparticles were successfully synthesized by simple oxidative polymerization of aniline in a two-phase system in the presence of poly(vinylpyrrolidone) (PVP) as a polymer shell agent, and citric acid was used as a doping acid instead of inorganic acids due to its better biocompatibility. TEM showed that the nanocomposites of PANi and PVP (PANi@PVP) assembled into core-shell like nanostructures uniformly. MTT results indicated that the PANi@PVP nanoparticles supported the survival of cells; IC50 could reach about 2.5 mg/mL, much higher than the IC50 value reported for PANi nanoparticles without PVP. Furthermore, in the presence of PVP, only exceeding PANi (>1.5 mg/mL) resulted in a comparable production of intracellular reactive oxygen species (ROS), the induction of apoptosis in PC-12 cells, and a weaker DNA fragmentation. TEM of PC-12 cell sections displayed that the cell morphological changes associated with the apoptosis were induced when exposed to a very high dose of PANi@PVP (3 mg/mL). The well-dispersed PANi@PVP combined with NIR irradiation achieved excellent photothermal conversion performance, which could kill cancer cell BEL-7402 in vitro effectively. Reflecting this well-dispersed property, the tumors in cancer bearing KM mice disappeared thoroughly after a single subcutaneous injection of PANi@PVP nanoparticles and subsequent NIR laser irradiation.

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