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1.
J Mater Sci Mater Med ; 26(9): 234, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26395359

RESUMEN

Bioreducible polymers have appeared as the ideal drug carriers for tumor therapy due to their properties of high stability in extracellular circulation and rapid drug release in intracellular reducing environment. Recently, the diselenide bond has emerged as a new reduction-sensitive linkage. In this work, the amphiphilic poly(ethylene glycol)-b-poly(L-lactide) containing diselenide bond has been synthesized and used to load anti-tumor drug, docetaxel (DTX), to form the redox micelles. It was found that the redox micelles showed a rapid response to glutataione (GSH), which resulted in a fast release of DTX in the presence of GSH. In contrast, <40 % of DTX was released from the micelles within 72 h under the normal condition (absence of GSH). The DTX-loaded redox micelles showed the significant inhibition effect to MCF-7 cells, and the cytotoxicity was dependent on the intracellular GSH concentrations. Moreover, considering the potentially clinical applications of the micelles through intravenous injection, the blood compatibility was also studied by the hemolysis analysis, activated partial thromboplastin time, prothrombin time and thromboelastography assays. These results confirmed that the redox micelles showed good blood safety, suggesting a potential application in tumor therapy.


Asunto(s)
Sistemas de Liberación de Medicamentos , Micelas , Poliésteres/química , Polietilenglicoles/química , Selenio/química , Glutatión/metabolismo , Hemólisis , Humanos , Células MCF-7 , Oxidación-Reducción
2.
Adv Mater ; 35(13): e2209041, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36754377

RESUMEN

Injectable hydrogels carrying therapeutic factors to modulate the infarct immune microenvironment show great potential in the treatment of myocardial infarction (MI). However, conventional injectable hydrogels release therapeutic factors in an uncontrolled manner, which leads to poor treatment efficacy and acute side effects on normal tissues. In this work, a matrix metalloproteinase (MMP)2/9-responsive hydrogel system (MPGC4) is developed, considering the characteristics of the post-MI microenvironment. MPGC4 consists of tetra-poly(ethylene glycol) (PEG) hydrogels and a composite gene nanocarrier (CTL4) that is composed of carbon dots (CDots) coupled with interleukin-4 plasmid DNA via electrostatic interactions. MPGC4 can be automatically triggered to release CTL4 on demand after MI to regulate the infarct immune microenvironment. In addition, due to the photoluminescence properties of CDots, a large amount of viscoelastic MPGC4 is found to be retained in situ after injection into the infarct region without leakage. The in vitro results demonstrate that CTL4 promotes proinflammatory M1 macrophage polarization to the anti-inflammatory M2 subtype and contributes to cardiomyocyte survival through macrophage transition. In a rat model of MI, MPGC4 clears MMPs and precisely targets CTL4 to the infarcted region. In particular, MPGC4 improves cardiac function by modulating macrophage transition to reduce early inflammatory responses and proangiogenic activity.


Asunto(s)
Hidrogeles , Infarto del Miocardio , Ratas , Animales , Hidrogeles/farmacología , Infarto del Miocardio/tratamiento farmacológico , Miocitos Cardíacos , Polietilenglicoles/uso terapéutico , Metaloproteinasas de la Matriz
3.
Adv Healthc Mater ; 12(1): e2201856, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36226990

RESUMEN

Conductive scaffolds are of great value for constructing functional myocardial tissues and promoting tissue reconstruction in the treatment of myocardial infarction (MI). Here, a novel scaffold composed of silk fibroin and polypyrrole (SP50) with a typical sponge-like porous structure and electrical conductivity similar to the native myocardium is developed. An electroactive engineered cardiac patch (SP50 ECP) with a certain thickness is constructed by applying electrical stimulation (ES) to the cardiomyocytes (CMs) on the scaffold. SP50 ECP can significantly express cardiac marker protein (α-actinin, Cx-43, and cTnT) and has better contractility and electrical coupling performance. Following in vivo transplantation, SP50 ECP shows a notable therapeutic effect in repairing infarcted myocardium. Not only can SP50 ECP effectively improves left ventricular remodeling and restore cardiac functions, such as ejection function (EF), but more importantly, improves the propagation of electrical pulses and promote the synchronous contraction of CMs in the scar area with normal myocardium, effectively reducing the susceptibility of MI rats to arrhythmias. In conclusion, this study demonstrates a facile approach to constructing electroactive ECPs based on porous conductive scaffolds and proves the therapeutic effects of ECPs in repairing the infarcted heart, which may represent a promising strategy for MI treatment.


Asunto(s)
Infarto del Miocardio , Polímeros , Ratas , Animales , Polímeros/química , Pirroles/química , Infarto del Miocardio/terapia , Miocardio , Miocitos Cardíacos , Conductividad Eléctrica , Andamios del Tejido/química
4.
J Cell Mol Med ; 16(6): 1310-20, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21838774

RESUMEN

In this study, an injectable, biodegradable hydrogel composite of oligo[poly(ethylene glycol) fumarate] (OPF) was investigated as a carrier of mouse embryonic stem cells (mESCs) for the treatment of myocardial infarction (MI). The OPF hydrogels were used to encapsulate mESCs. The cell differentiation in vitro over 14 days was determined via immunohistochemical examination. Then, mESCs encapsulated in OPF hydrogels were injected into the LV wall of a rat MI model. Detailed histological analysis and echocardiography were used to determine the structural and functional consequences after 4 weeks of transplantation. With ascorbic acid induction, mESCs could differentiate into cardiomyocytes and other cell types in all three lineages in the OPF hydrogel. After transplantation, both the 24-hr cell retention and 4-week graft size were significantly greater in the OPF + ESC group than that of the PBS + ESC group (P < 0.01). Four weeks after transplantation, OPF hydrogel alone significantly reduced the infarct size and collagen deposition and improved the cardiac function. The heart function and revascularization improved significantly, while the infarct size and fibrotic area decreased significantly in the OPF + ESC group compared with that of the PBS + ESC, OPF and PBS groups (P < 0.01). All treatments had significantly reduced MMP2 and MMP9 protein levels compared to the PBS control group, and the OPF + ESC group decreased most by Western blotting. Transplanted mESCs expressed cardiovascular markers. This study suggests the potential of a method for heart regeneration involving OPF hydrogels for stem cell encapsulation and transplantation.


Asunto(s)
Materiales Biocompatibles/química , Células Madre Embrionarias/trasplante , Hidrogeles/química , Infarto del Miocardio/terapia , Animales , Diferenciación Celular , Línea Celular , Modelos Animales de Enfermedad , Células Madre Embrionarias/citología , Células Madre Embrionarias/metabolismo , Femenino , Inyecciones , Ratones , Infarto del Miocardio/patología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/trasplante , Poliésteres/química , Polietilenglicoles/química , Ratas , Ratas Sprague-Dawley
5.
ACS Nano ; 16(10): 16234-16248, 2022 10 25.
Artículo en Inglés | MEDLINE | ID: mdl-36190461

RESUMEN

Although hydrogel-based patches have shown promising therapeutic efficacy in myocardial infarction (MI), synergistic mechanical, electrical, and biological cues are required to restore cardiac electrical conduction and diastolic-systolic function. Here, an injectable mechanical-electrical coupling hydrogel patch (MEHP) is developed via dynamic covalent/noncovalent cross-linking, appropriate for cell encapsulation and minimally invasive implantation into the pericardial cavity. Pericardial fixation and hydrogel self-adhesiveness properties enable the MEHP to highly compliant interfacial coupling with cyclically deformed myocardium. The self-adaptive MEHP inhibits ventricular dilation while assisting cardiac pulsatile function. The MEHP with the electrical conductivity and sensitivity to match myocardial tissue improves electrical connectivity between healthy and infarcted areas and increases electrical conduction velocity and synchronization. Overall, the MEHP combined with cell therapy effectively prevents ventricular fibrosis and remodeling, promotes neovascularization, and restores electrical propagation and synchronized pulsation, facilitating the clinical translation of cardiac tissue engineering.


Asunto(s)
Hidrogeles , Infarto del Miocardio , Humanos , Hidrogeles/farmacología , Hidrogeles/uso terapéutico , Miocardio , Infarto del Miocardio/tratamiento farmacológico , Conductividad Eléctrica , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacología
6.
J Cell Mol Med ; 14(5): 1044-55, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20193036

RESUMEN

Future perspectives Heart disease is a leading cause of morbidity and mortality worldwide. Myocardial infarction leads to permanent loss of cardiac tissue and ultimately heart failure. However, current therapies could only stall the progression of the disease. Thus, new therapies are needed to regenerate damaged hearts to overcome poor prognosis of patients with heart failure. The shortage of heart donors is also a factor for innovating new therapies. Although the cardiac performance by cell-based therapy has improved, unsatisfactory cell retention and transplant survival still plague this technique. Because biomaterials can improve the cell retention, survival and differentiation, cardiac tissue engineering is now being explored as an approach to support cell-based therapies and enhance their efficacy for cardiac disease. In the last decade, cardiac tissue engineering has made considerable progress. Among different kinds of approaches in the cardiac tissue engineering, the approach of injectable cardiac tissue engineering is more minimally invasive than that of in vitro engineered tissue or epicardial patch implantation. It is therefore clinically appealing. In this review, we strive to describe the major progress in the filed of injectable cardiac tissue engineering, including seeding cell sources, biomaterials and novel findings in preclinical studies and clinical applications. The remaining problems will also be discussed.


Asunto(s)
Infarto del Miocardio/terapia , Miocardio/patología , Ingeniería de Tejidos/métodos , Materiales Biocompatibles/uso terapéutico , Células Madre Embrionarias/citología , Humanos , Inyecciones
7.
Biomater Sci ; 8(11): 3173-3185, 2020 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-32367084

RESUMEN

The development of three-dimensional conductive scaffolds is vital to support the adhesion, proliferation and myocardial differentiation of stem cells in cardiac tissue engineering. Herein, we describe a facile approach for preparing a poly(3,4-ethylenedioxythiophene)/alginate (PEDOT/Alg) porous scaffold with a wide range of desirable properties. In the PEDOT/Alg scaffold, chemically crosslinked alginate networks are formed using adipic acid hydrazide as the crosslinker, and PEDOT is synthesized in situ in the alginate matrix simultaneously. PEDOT exists in the alginate matrix as particles and its morphology can be modulated by adjusting the ratio of PEDOT/alginate. The results also show that the swelling properties, degradation behaviors, mechanical strength and conductivity of the PEDOT/Alg scaffold can be controlled via adjusting the PEDOT/alginate ratio. The introduction of PEDOT can overcome the brittle nature of the pure alginate scaffold. Moreover, the PEDOT/Alg scaffold exhibits excellent conductivity (as high as 6 × 10-2 S cm-1). The introduction of PEDOT improves the protein absorption capacity of the alginate scaffold. To explore its potential application in cardiac tissue engineering, brown adipose-derived stem cells (BADSCs) are seeded in the prepared PEDOT/Alg porous scaffold. The results suggest that the PEDOT/Alg porous scaffold can support the attachment and proliferation of BADSCs. Moreover, it is beneficial for the cardiomyogenic differentiation of BADSCs, especially under electrical stimulation. Overall, we conclude that the PEDOT/Alg porous scaffold may represent an ideal platform to modulate the biological behaviors of BADSCs.


Asunto(s)
Tejido Adiposo Pardo/citología , Alginatos/química , Compuestos Bicíclicos Heterocíclicos con Puentes/química , Polímeros/química , Células Madre/fisiología , Andamios del Tejido , Adsorción , Diferenciación Celular , Proliferación Celular , Conductividad Eléctrica , Estimulación Eléctrica , Microscopía Electrónica de Rastreo , Miocardio , Porosidad , Proteínas/química , Células Madre/ultraestructura
8.
J Biomed Nanotechnol ; 14(6): 1099-1106, 2018 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-29843874

RESUMEN

Optical electrodes are important tools for optogenetic research. Flexible optical electrodes represent a refinement over traditional fiber-based electrodes because they contact with target cells gently by reducing mechanical mismatch, thereby enhancing their long-term, stable signal acquisition capability. Until now, little attention has been paid to flexible intracortical optical electrodes. Here, we reported a novel flexible penetrating optical electrode with a probe made of composite hydrogels. We used polydimethylsiloxane (PDMS), a kind of transparent material, to fabricate waveguide by capillary assembly method with two tungsten wires inside providing mechanic support. Then one tungsten wire was withdrawn out and the microchannel was filled with hydrogel composed of polyvinyl alcohol (PVA), multi-walled carbon nanotubes (MWCNT), poly(3,4-ethylenedioxythiophene) (PEDOT), and polystyrene sulfonate (PSS) as an electrical recording and stimulation probe. With PDMS as the waveguide and PVA/MWCNT/PEDOT/PSS hydrogel as the electroprobe, the optical electrode becomes a flexible package. The morphology observed by scanning electron microscopy showed that the PVA/MWCNT/PEDOT/PSS hydrogel had a loose surface structure, which would allow the effective adhesion to target neurons. A buckling test showed that our electrode maintained bending strength comparable to that of previously reported flexible penetrating electrodes. Finally, the electrical properties showed a lower impedance and higher charge capacity after PEDOT/PSS modification. The flexible penetrating optical electrode we developed may be used for long-term in vivo optogenetics studies.


Asunto(s)
Optogenética , Dimetilpolisiloxanos , Electrodos , Hidrogeles , Nanotubos de Carbono
9.
Biomaterials ; 157: 149-160, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29272722

RESUMEN

Brown adipose derived stem cells (BADSCs) have become a promising stem cell treatment candidate for myocardial infarction because of their efficiently spontaneous differentiation capacity towards cardiomyocytes. The lack of existing cell passage protocols motivates us to develop a neotype 3D cell expansion technique for BADSCs. In this study, "clickable" zwitterionic starch based hydrogels are developed using methacrylate modified sulfobetaine derived starch with dithiol-functionalized poly (ethylene glycol) as crosslinker via the "thiol-ene" Michael addition reaction. Moreover, CGRGDS peptide is immobilized into the hydrogel via a similar "clickable" approach. Their Young's moduli range from 22.28 to 74.81 kPa depending on the concentration of precursor solutions. Excellent anti-fouling property is also presented owing to the introduction of zwitterionic moieties. BADSCs are homogeneously encapsulated in the hydrogels and then routinely cultured for 10 days. Results suggest a capacious cell proliferation and the extent increases with either the decrease of mechanical strength or the introduction of CGRGDS. More excitingly, the cell "stemness" is well maintained during this period and the expanded cells released from the hydrogels well keep the efficiently spontaneous cardiomyogenic differentiation capacity. Therefore, it is suggested that zwitterionic starch based hydrogel is able for the expansion and "stemness " maintenance of BADSCs.


Asunto(s)
Tejido Adiposo Pardo/citología , Materiales Biocompatibles/farmacología , Diferenciación Celular/efectos de los fármacos , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacología , Almidón/química , Células Madre/citología , Ingeniería de Tejidos/métodos , Tejido Adiposo Pardo/efectos de los fármacos , Animales , Materiales Biocompatibles/química , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Ensayo de Materiales , Oligopéptidos/química , Ratas , Ratas Sprague-Dawley , Células Madre/efectos de los fármacos
10.
Theranostics ; 8(12): 3317-3330, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29930732

RESUMEN

After myocardial infarction (MI), the scar tissue contributes to ventricular dysfunction by electrically uncoupling viable cardiomyocytes in the infarct region. Injection of a conductive hydrogel could not only provide mechanical support to the infarcted region, but also synchronize contraction and restore ventricular function by electrically connecting isolated cardiomyocytes to intact tissue. Methods: We created a conductive hydrogel by introducing graphene oxide (GO) nanoparticles into oligo(poly(ethylene glycol) fumarate) (OPF) hydrogels. The hydrogels were characterized by AFM and electrochemistry workstation. A rat model of myocardial infarction was used to investigate the ability of OPF/GO to improve cardiac electrical propagation in the injured heart in vivo. Echocardiography (ECHO) was used to evaluate heart function 4 weeks after MI. Ca2+ imaging was used to visualize beating cardiomyocytes (CMs). Immunofluorescence staining was used to visualize the expression of cardiac-specific markers. Results: OPF/GO hydrogels had semiconductive properties that were lacking in pure OPF. In addition, the incorporation of GO into OPF hydrogels could improve cell attachment in vitro. Injection of OPF/GO 4 weeks after myocardial infarction in rats enhanced the Ca2+ signal conduction of cardiomyocytes in the infarcted region in comparison with PBS or OPF alone. Moreover, the injection of OPF/GO hydrogel into the infarct region enhanced the generation of cytoskeletal structure and intercalated disc assembly. Echocardiography analysis showed improvement in load-dependent ejection fraction/fractional shortening of heart function 4 weeks after injection. Conclusions: We prepared a conductive hydrogel (OPF/GO) that provide mechanical support and biological conduction in vitro and in vivo. We found that injected OPF/GO hydrogels can provide mechanical support and electric connection between healthy myocardium and the cardiomyocytes in the scar via activating the canonical Wnt signal pathway, thus upregulating the generation of Cx43 and gap junction associated proteins. Injection of OPF/GO hydrogel maintained better heart function after myocardial infarction than the injection of a nonconductive polymer.


Asunto(s)
Conductividad Eléctrica , Grafito/administración & dosificación , Hidrogel de Polietilenoglicol-Dimetacrilato/administración & dosificación , Infarto del Miocardio/tratamiento farmacológico , Poliésteres/administración & dosificación , Polietilenglicoles/administración & dosificación , Animales , Modelos Animales de Enfermedad , Ecocardiografía , Técnica del Anticuerpo Fluorescente , Inyecciones , Infarto del Miocardio/patología , Imagen Óptica , Ratas , Resultado del Tratamiento
11.
Mater Sci Eng C Mater Biol Appl ; 70(Pt 1): 572-585, 2017 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-27770930

RESUMEN

It is a promising way to treat the multi drug resistance (MDR) of tumor cells in both of drug and gene methods. A polyamidoamne dendrimer functionalized graphene oxide (GO-PAMAM) was designed, which could load doxorubicin (DOX) and MMP-9 shRNA plasmid at the same time in order to achieve effective treatment to breast cancer. GO-PAMAM has a high loading capacity to DOX and pH-controlled DOX release. Besides, it has efficient gene transfer ability, the transfection efficiency is significantly better than PEI-25k in the presence of serum, and it can significantly inhibit the expression of MMP-9 protein in MCF-7 cells. The effect of DOX and MMP-9 shRNA plasmid co-delivery was more significant than that of the single drug. Moreover, GO-PAMAM exhibited lower cytotoxicity compared to PEI-25k in CCK-8 assays, and also showed a good biocompatibility in vivo. Therefore, GO-PAMAM will have broad prospects for drug and gene co-delivery.


Asunto(s)
Dendrímeros/química , Doxorrubicina/farmacología , Sistemas de Liberación de Medicamentos , Técnicas de Transferencia de Gen , Grafito/química , Plásmidos/administración & dosificación , ARN Interferente Pequeño/administración & dosificación , Células 3T3 , Animales , Apoptosis/efectos de los fármacos , Materiales Biocompatibles/farmacología , Supervivencia Celular/efectos de los fármacos , ADN/metabolismo , Dendrímeros/síntesis química , Liberación de Fármacos , Electroforesis en Gel de Agar , Citometría de Flujo , Humanos , Concentración 50 Inhibidora , Células MCF-7 , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Espectroscopía Infrarroja por Transformada de Fourier , Espectrometría Raman , Electricidad Estática , Termogravimetría , Transfección
12.
J Tissue Eng Regen Med ; 11(12): 3544-3555, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-28326684

RESUMEN

Burn infection is a serious problem that delays wound healing and leads to death. Curcumin (Cur) has been shown to exhibit antioxidant, anti-inflammatory, antimicrobial and anticarcinogenic activity. However, its instability, extremely low aqueous solubility and bioavailability in physiological fluids may make it difficult to maintain local Cur concentrations above the minimum inhibitory concentration for burn infection treatment. The objective of this study was to construct complexes of Cur/gelatin microspheres (GMs) and porous collagen (Coll)-cellulose nanocrystals (CNCs) composite scaffolds for full-thickness burn infection treatment. The Cur/GMs/Coll-CNCs scaffolds had high porosity, available pore size, and a long and sustained Cur release profile. Furthermore, the composite scaffold exhibited remarkably strong antibacterial activity. Hence, we evaluated the wound-healing effects and antibacterial properties of Cur/GMs/Coll-CNCs scaffolds in a rat full-thickness burn infection model. The Cur/GMs/Coll-CNCs scaffold was able to prevent not only local inflammation but also accelerated dermis regeneration. Thus, we conclude that Cur/GMs/Coll-CNCs scaffolds can act as an effective dermal regeneration template for full-thickness burn wound infection healing in rats models. Copyright © 2017 John Wiley & Sons, Ltd.


Asunto(s)
Quemaduras/tratamiento farmacológico , Celulosa/farmacología , Colágeno/farmacología , Curcumina/uso terapéutico , Microesferas , Nanopartículas/química , Regeneración/efectos de los fármacos , Animales , Antibacterianos/farmacología , Bovinos , Curcumina/farmacología , Liberación de Fármacos , Inmunohistoquímica , Interleucina-1beta/metabolismo , Masculino , Pruebas de Sensibilidad Microbiana , Ratas Sprague-Dawley , Piel/patología , Andamios del Tejido/química , Factor de Necrosis Tumoral alfa/metabolismo , Cicatrización de Heridas/efectos de los fármacos
13.
J Biomed Mater Res A ; 104(3): 802-812, 2016 03.
Artículo en Inglés | MEDLINE | ID: mdl-26481428

RESUMEN

Amphiphilic block copolymer methoxy polyethyleneglycol-polycaprolactone (mPEG-PCL) has attracted interest in the biomedical field, due to its water solubility and biodegradability. Nevertheless, the blood safety of mPEG-PCL copolymers has not been investigated in detail. Because mPEG-PCL copolymers introduced in vivo would inevitably interact with blood tissue, an investigation of possible interactions of mPEG-PCL with key blood components is crucial. We studied the effects of two mPEG-PCL copolymer solutions on blood coagulation, the morphology and lysis of human red blood cells (RBCs), the structure of plasma fibrinogen, complement activation, and platelet aggregation. We found that higher concentrations of the mPEG-PCL copolymers impaired blood clotting, and the copolymers had little impact on the morphology or lysis of RBCs. From the spectroscopy results, the copolymers affected the local microstructure of fibrinogen. The copolymers significantly activated the complement system in a concentration-dependent way. At higher concentrations, the copolymers impaired platelet aggregation, which may have been mediated by an inhibition of the arachidonic acid pathway. These findings provide important information that may be useful for the molecular design and biomedical applications of mPEG-PCL copolymers. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 802-812, 2016.


Asunto(s)
Ensayo de Materiales/métodos , Poliésteres/farmacología , Polietilenglicoles/farmacología , Adenosina Difosfato/farmacología , Ácido Araquidónico/farmacología , Coagulación Sanguínea/efectos de los fármacos , Forma de la Célula/efectos de los fármacos , Dicroismo Circular , Activación de Complemento/efectos de los fármacos , Complemento C3a/metabolismo , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Fibrinógeno/metabolismo , Hemólisis/efectos de los fármacos , Hemorreología/efectos de los fármacos , Humanos , Cinética , Tiempo de Tromboplastina Parcial , Agregación Plaquetaria/efectos de los fármacos , Tiempo de Protrombina , Soluciones , Espectrometría de Fluorescencia , Tromboelastografía , Tromboxano B2/metabolismo
14.
Mater Sci Eng C Mater Biol Appl ; 62: 173-82, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26952412

RESUMEN

The development of safe and efficient gene carriers is the key to the clinical success of gene therapy. In the present study, carboxymethyl chitosan (CMCS) was prepared by chitosan (CS) alkalisation and carboxymethylation reactions. Then polyethyleneimine (PEI) was grafted to the backbone of CMCS by an amidation reaction. The CMCS-PEI copolymer showed strong complexation capability with DNA to form nanoparticles, and achieved lower cytotoxicity and higher transfection efficiency compared with PEI (25 kDa) towards 293T and 3T3 cells. Moreover, the haemocompatibility of the CMCS-PEI copolymer was investigated through the aggregation, morphology and lysis of human red blood cells (RBCs), along with the impact on the clotting function with activated partial thromboplastin time (APTT), prothrombin time (PT) and thromboelastographic (TEG) assays. The results demonstrated that the CMCS-PEI copolymer with a concentration lower than 0.05 mg/mL had little impact on the aggregation, morphology or lysis of RBCs, or on blood coagulation. Therefore, the copolymer may be a strong alternative candidate as an effective and safe non-viral vector.


Asunto(s)
Materiales Biocompatibles/química , Quitosano/análogos & derivados , Polietileneimina/análogos & derivados , Transfección , Animales , Materiales Biocompatibles/toxicidad , Línea Celular , Supervivencia Celular/efectos de los fármacos , Quitosano/química , Quitosano/toxicidad , Electroforesis en Gel de Agar , Eritrocitos/citología , Eritrocitos/efectos de los fármacos , Células HEK293 , Hemólisis/efectos de los fármacos , Humanos , Ratones , Microscopía Electrónica de Transmisión , Tiempo de Tromboplastina Parcial , Tamaño de la Partícula , Plásmidos/metabolismo , Polietileneimina/química , Polietileneimina/toxicidad , Tiempo de Protrombina , Tromboelastografía
15.
Adv Healthc Mater ; 5(4): 474-88, 2016 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-26626543

RESUMEN

Cardiac tissue engineering is an effective method to treat the myocardial infarction. However, the lack of electrical conductivity of biomaterials limits their applications. In this work, a homogeneous electronically conductive double network (HEDN) hydrogel via one-step facile strategy is developed, consisting of a rigid/hydrophobic/conductive network of chemical crosslinked poly(thiophene-3-acetic acid) (PTAA) and a flexible/hydrophilic/biocompatible network of photo-crosslinking methacrylated aminated gelatin (MAAG). Results suggest that the swelling, mechanical, and conductive properties of HEDN hydrogel can be modulated via adjusting the ratio of PTAA network to MAAG network. HEDN hydrogel has Young's moduli ranging from 22.7 to 493.1 kPa, and its conductivity (≈10(-4) S cm(-1)) falls in the range of reported conductivities for native myocardium tissue. To assess their biological activity, the brown adipose-derived stem cells (BADSCs) are seeded on the surface of HEDN hydrogel with or without electrical stimulation. Our data show that the HEDN hydrogel can support the survival and proliferation of BADSCs, and that it can improve the cardiac differentiation efficiency of BADSCs and upregulate the expression of connexin 43. Moreover, electrical stimulation can further improve this effect. Overall, it is concluded that the HEDN hydrogel may represent an ideal scaffold for cardiac tissue engineering.


Asunto(s)
Conductividad Eléctrica , Hidrogeles/química , Miocitos Cardíacos/citología , Células Madre/citología , Ingeniería de Tejidos , Acetatos/química , Tejido Adiposo Pardo/citología , Animales , Materiales Biocompatibles/química , Diferenciación Celular , Proliferación Celular , Supervivencia Celular/efectos de los fármacos , Conexina 43/genética , Conexina 43/metabolismo , Módulo de Elasticidad , Gelatina/química , Ratones , Tiofenos/química , Andamios del Tejido/química , Regulación hacia Arriba
16.
ACS Appl Mater Interfaces ; 8(20): 12609-19, 2016 05 25.
Artículo en Inglés | MEDLINE | ID: mdl-27153187

RESUMEN

The drug/gene codelivery is a promising strategy for cancer treatment. Herein, to realize the codelivery of docetaxel and MMP-9 siRNA plasmid efficiently into tumor cells, a star-shaped amphiphilic copolymer consisting of hyperbranched polyglycerol derivative (HPG-C18) and dendritic poly(l-lysine) (PLLD) was synthesized by the click reaction between azido-modified HPG-C18 and propargyl focal point PLLD. The obtained HPG-C18-PLLD could form the nanocomplexes with docetaxel and MMP-9, and the complexes showed good gene delivery ability in vitro by inducing an obvious decrease in MMP-9 protein expression in MCF-7 cells. The apoptosis assay showed that the complex could induce a more significant apoptosis to breast cancer cells than that of docetaxel or MMP-9 used alone. In vivo assay indicated that the codelivery strategy displayed a better effect on tumor inhibition. Moreover, HPG-C18-PLLD displayed lower toxicity as well as better blood compatibility compared to polyethylenimine PEI-25k, which may be the result of that HPG-C18-PLLD showed the comparative MMP-9 delivery ability in vivo compared with PEI-25k even if it showed the slight lower transfection efficiency in vitro. Therefore, HPG-C18-PLLD is a safe and effective carrier for the codelivery of drug/gene, which should be encouraged in tumor therapy.


Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Glicerol/química , Neoplasias/terapia , Polilisina/química , Polímeros/química , ARN Interferente Pequeño/administración & dosificación , Taxoides/administración & dosificación , Línea Celular Tumoral , Docetaxel , Humanos , Células MCF-7 , Neoplasias/tratamiento farmacológico
17.
Acta Biomater ; 15: 65-76, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25575852

RESUMEN

The foreign-body response to biomaterials compromises the performance of many biomedical devices by severe fibrosis and limited neovascularization. Mesenchymal stem cells are known to secrete cytokines for treating inflammatory conditions. In this study, we aim to investigate whether the paracrine products of adipose-derived mesenchymal stem cells (ADSCs) can affect the microenvironment of biomaterials and improve tissue responses to biomaterial implants. A model system was built by loading ADSC spheroids into a macroencapsulation device composed of polytetrafluoroethylene (PTFE) filtration membranes. Soluble ADSC factors that diffused out of the device in vitro promoted the angiogenetic activity of endothelial cells and affected the secretion pattern of macrophages. In vivo study was carried out by subcutaneously embedding blank or ADSC-laden devices in rats. Following a 4 week implantation, the ADSC-laden devices were better vascularized and induced significantly less fibrotic tissue formation in comparison to the non-cellular controls. This study may facilitate our understanding of foreign-body responses and suggest new ways to improve the tissue reaction of biomedical devices for cell-based therapy.


Asunto(s)
Tejido Adiposo/citología , Materiales Biocompatibles/farmacología , Ensayo de Materiales/instrumentación , Células Madre Mesenquimatosas/citología , Neovascularización Fisiológica/efectos de los fármacos , Comunicación Paracrina/efectos de los fármacos , Animales , Antiinflamatorios/farmacología , Células Inmovilizadas/citología , Células Inmovilizadas/efectos de los fármacos , Técnicas de Cocultivo , Medios de Cultivo Condicionados/farmacología , Fibrosis , Regulación de la Expresión Génica/efectos de los fármacos , Imagenología Tridimensional , Implantes Experimentales , Masculino , Células Madre Mesenquimatosas/efectos de los fármacos , Neovascularización Fisiológica/genética , Ratas Sprague-Dawley , Esferoides Celulares/citología , Esferoides Celulares/efectos de los fármacos
18.
ACS Appl Mater Interfaces ; 7(12): 6505-17, 2015 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-25756853

RESUMEN

Myocardial infarction (MI) still represents the "Number One Killer" in the world. The lack of functional vasculature of the infracted myocardium under hypoxia is one of the main problems for cardiac repair. In this study, a thermosensitive chitosan chloride-RoY (CSCl-RoY) hydrogel was developed to improve angiogenesis under hypoxia after MI. First, RoY peptides were conjugated onto the CSCl chain via amide linkages, and our data show that the conjugation of RoY peptide to CSCl does not interfere with the temperature sensitivity. Then, the effect of CSCl-RoY hydrogels on vascularization in vitro under hypoxia was investigated using human umbilical vein endothelial cells (HUVECs). Results show that CSCl-RoY hydrogels can promote the survival, proliferation, migration and tube formation of HUVECs under hypoxia compared with CSCl hydrogel. Further investigations suggest that CSCl-RoY hydrogels can modulate the expression of membrane surface GRP78 receptor of HUVECs under hypoxia and then activate Akt and ERK1/2 signaling pathways related to cell survival/proliferation, thereby enhancing angiogenic activity of HUVECs under hypoxia. To assess its therapeutic properties in vivo, a MI model was induced in rats by the left anterior descending artery ligation. CSCl or CSCl-RoY hydrogels were injected into the border of infracted hearts. The results demonstrate that the introduction of RoY peptide can not only improve angiogenesis at MI region but also improve the cardiac functions. Overall, we conclude that the CSCl-RoY may represent an ideal scaffold material for injectable cardiac tissue engineering.


Asunto(s)
Quitosano/química , Corazón/fisiopatología , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Hipoxia/fisiopatología , Neovascularización Fisiológica , Péptidos/química , Ingeniería de Tejidos/instrumentación , Andamios del Tejido/química , Animales , Proliferación Celular , Supervivencia Celular , Quitosano/administración & dosificación , Chaperón BiP del Retículo Endoplásmico , Corazón/crecimiento & desarrollo , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Células Endoteliales de la Vena Umbilical Humana/citología , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Hidrogel de Polietilenoglicol-Dimetacrilato/administración & dosificación , Hipoxia/tratamiento farmacológico , Hipoxia/genética , Hipoxia/metabolismo , Masculino , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/genética , Infarto del Miocardio/metabolismo , Infarto del Miocardio/fisiopatología , Péptidos/administración & dosificación , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de Señal
19.
Nanoscale ; 7(44): 18677-85, 2015 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-26499788

RESUMEN

The development of coating materials for neural interfaces has been a pursued to improve the electrical, mechanical and biological performances. For these goals, a bioactive coating was developed in this work featuring a poly(3,4-ethylenedioxythiophene) (PEDOT)/carbon nanotube (CNT) composite and covalently bonded YIGSR and RGD. Its biological effect and electrical characteristics were assessed in vivo on microwire arrays (MWA). The coated electrodes exhibited a significantly higher charge storage capacity (CSC) and lower electrochemical impedance at 1 kHz which are desired to improve the stimulating and recording performances, respectively. Acute neural recording experiments revealed that coated MWA possess a higher signal/noise ratio capturing spikes undetected by uncoated electrodes. Moreover, coated MWA possessed more active sites and single units, and the noise floor of coated electrodes was lower than that of uncoated electrodes. There is little information in the literature concerning the chronic performance of bioactively modified neural interfaces in vivo. Therefore in this work, chronic in vivo tests were conducted and the PEDOT/PSS/MWCNT-polypeptide coated arrays exhibited excellent performances with the highest mean maximal amplitude from day 4 to day 12 during which the acute response severely compromised the performance of the electrodes. In brief, we developed a simple method of covalently bonding YIGSR and RGD to a PEDOT/PSS/MWCNT-COOH composite improving both the biocompatibility and electrical performance of the neural interface. Our findings suggest that YIGSR and RGD modified PEDOT/PSS/MWCNT is a promising bioactivated composite coating for neural recording and stimulating.


Asunto(s)
Compuestos Bicíclicos Heterocíclicos con Puentes , Ensayo de Materiales , Nanotubos de Carbono/química , Nanocables/química , Neuronas/metabolismo , Oligopéptidos , Polímeros , Animales , Compuestos Bicíclicos Heterocíclicos con Puentes/química , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Neuronas/citología , Oligopéptidos/química , Oligopéptidos/farmacología , Células PC12 , Polímeros/química , Polímeros/farmacología , Ratas
20.
Biomaterials ; 35(13): 3986-98, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24508080

RESUMEN

The ability to restore heart function by replacement of diseased myocardium is one of the great challenges in biomaterials and regenerative medicine. Brown adipose derived stem cells (BADSCs) present a new source of cardiomyocytes to regenerate the myocardium after infarction. In this study, we explored an injectable tissue engineering strategy to repair damaged myocardium, in which chitosan hydrogels were investigated as a carrier for BADSCs. In vitro, the effect and mechanism of chitosan components on the cardiac differentiation of BADSCs were investigated. In vivo, BADSCs carrying double-fusion reporter gene (firefly luciferase and monomeric red fluorescent protein (fluc-mRFP)) were transplanted into infarcted rat hearts with or without chitosan hydrogel. Multi-techniques were used to assess the effects of treatments. We observed that chitosan components significantly enhanced cardiac differentiation of BADSCs, which was assessed by percentages of cTnT(+) cells and expression of cardiac-specific markers, including GATA-4, Nkx2.5, Myl7, Myh6, cTnI, and Cacna1a. Treatment with collagen synthesis inhibitors, cis-4-hydroxy-D-proline (CIS), significantly inhibited the chitosan-enhanced cardiac differentiation, indicating that the enhanced collagen synthesis by chitosan accounts for its promotive role in cardiac differentiation of BADSCs. Longitudinal in vivo bioluminescence imaging and histological staining revealed that chitosan enhanced the survival of engrafted BADSCs and significantly increased the differentiation rate of BADSCs into cardiomyocytes in vivo. Furthermore, BADSCs delivered by chitosan hydrogel prevented adverse matrix remodeling, increased angiogenesis, and preserved heart function. These results suggested that the injectable cardiac tissue engineering based on chitosan hydrogel and BADSCs is a useful strategy for myocardium regeneration.


Asunto(s)
Tejido Adiposo Pardo/citología , Quitosano/química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Infarto del Miocardio/terapia , Ingeniería de Tejidos/métodos , Animales , Diferenciación Celular/genética , Diferenciación Celular/fisiología , Células Cultivadas , Masculino , Ratas , Ratas Sprague-Dawley
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