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1.
Biomater Adv ; 154: 213615, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37716334

RESUMO

Hyaluronic acid/silk fibroin (HA/SF or HS) hydrogels with remarkable mechanical characteristics have been reported as tissue engineering biomaterials. Herein, the addition of dopamine/polydopamine (DA/PDA) to HS hydrogels to develop multifunctional HA/PDA/SF (or HDS) hydrogels for the delivery of drugs such as N-acetyl-L-cysteine (NAC) from nasal to brain tissue is examined. Herein, DA-dependent functions of HDS hydrogels with highly adhesive forces, photothermal response (PTR) effects generated by near infrared (NIR) irradiation, and anti-oxidative effects were demonstrated. An in-vitro study shows that the HDS/NAC hydrogels could open tight junctions in the RPMI 2650 cell line, a model cell of the nasal mucosa, as demonstrated by the decreased values of transepithelial electrical resistance (TEER) and more discrete ZO-1 staining than those for the control group. This effect was markedly enhanced by NIR irradiation of the HDS/NAC-NIR hydrogels. Compared to the results obtained using NAC solution, an in-vivo imaging study (IVIS) in rats showed an approximately nine-fold increase in the quantity of NAC delivered from the nasal cavity to the brain tissue in the span of 2 h through the PTR effect generated by the NIR irradiation of the nasal tissue and administration of the HDS/NAC hydrogels. Herein, dopamine-dependent multifunctional HDS hydrogels were studied, and the nasal administration of HDS/NAC-NIR hydrogels with PTR effects generated by NIR irradiation was found to have significantly enhanced NAC delivery to brain tissues.


Assuntos
Fibroínas , Ratos , Animais , Acetilcisteína/farmacologia , Ácido Hialurônico/farmacologia , Dopamina/farmacologia , Hidrogéis/farmacologia , Cavidade Nasal , Encéfalo
2.
Pharmaceutics ; 14(6)2022 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-35745861

RESUMO

Using nasal routes to deliver drugs to the brain using multifunctional nanoparticles (NPs) to bypass the blood-brain barrier (BBB) might enhance the delivery efficacy. Anti-oxidative N-Acetyl-L-cysteine (NAC)-loaded silk fibroin (SF/NAC) NPs are produced, characterized and studied as a potential delivery vehicle for NAC delivered to the brain via nasal for both in vitro and in vivo studies. The NPs are not cytotoxic to RPMI 2650 cells, mucosal model cells, at a concentration of 6000 µg/mL. The anti-oxidative activities of SF/NAC NPs are demonstrated by high H2O2 scavenge capacities of the NPs and shown by mitochondrial superoxide (MitoSOX) immunostaining of human mesenchymal stem cells. Tight junctions in RPMI 2650 cells are opened after 30 min of incubation with SF/NAC NPs, which are demonstrated by measuring the decrease in trans-epithelial electrical resistance (TEER) values and discreteness in ZO-1 stains. The cellular uptake of SF/NAC NPs by RPMI 2650 cells is significantly greater than that for SF NPs and increased with increasing incubation time. In an in vivo imaging study (IVIS) using rats shows that the amount of NAC that is delivered to the brain by SF/NAC NPs increased by 1.40-2.60 times and NAC is retained longer in the nasal cavity than NAC solutions in a 2-h study.

3.
Molecules ; 27(9)2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35566251

RESUMO

Hydrogels are crosslinked polymer chains with three-dimensional (3D) network structures, which can absorb relatively large amounts of fluid. Because of the high water content, soft structure, and porosity of hydrogels, they closely resemble living tissues. Research in recent years shows that hydrogels have been applied in various fields, such as agriculture, biomaterials, the food industry, drug delivery, tissue engineering, and regenerative medicine. Along with the underlying technology improvements of hydrogel development, hydrogels can be expected to be applied in more fields. Although not all hydrogels have good biodegradability and biocompatibility, such as synthetic hydrogels (polyvinyl alcohol, polyacrylamide, polyethylene glycol hydrogels, etc.), their biodegradability and biocompatibility can be adjusted by modification of their functional group or incorporation of natural polymers. Hence, scientists are still interested in the biomedical applications of hydrogels due to their creative adjustability for different uses. In this review, we first introduce the basic information of hydrogels, such as structure, classification, and synthesis. Then, we further describe the recent applications of hydrogels in 3D cell cultures, drug delivery, wound dressing, and tissue engineering.


Assuntos
Hidrogéis , Engenharia Tecidual , Materiais Biocompatíveis/química , Sistemas de Liberação de Medicamentos , Hidrogéis/química , Hidrogéis/uso terapêutico , Polímeros/química
4.
Nat Biomed Eng ; 6(4): 421-434, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34811487

RESUMO

Pacemaker cells can be differentiated from stem cells or transdifferentiated from quiescent mature cardiac cells via genetic manipulation. Here we show that the exposure of rat quiescent ventricular cardiomyocytes to a silk-fibroin hydrogel activates the direct conversion of the quiescent cardiomyocytes to pacemaker cardiomyocytes by inducing the ectopic expression of the vascular endothelial cell-adhesion glycoprotein cadherin. The silk-fibroin-induced pacemaker cells exhibited functional and morphological features of genuine sinoatrial-node cardiomyocytes in vitro, and pacemaker cells generated via the injection of silk fibroin in the left ventricles of rats functioned as a surrogate in situ sinoatrial node. Biomaterials with suitable surface structure, mechanics and biochemistry could facilitate the scalable production of biological pacemakers for human use.


Assuntos
Fibroínas , Miócitos Cardíacos , Animais , Materiais Biocompatíveis , Diferenciação Celular , Fibroínas/metabolismo , Fibroínas/farmacologia , Ratos , Nó Sinoatrial/metabolismo
5.
Int J Biol Macromol ; 185: 122-133, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34147523

RESUMO

Photothermal-responsive (PTR) and anti-oxidative silk fibroin/dopamine nanoparticles (SD NPs) mediated by tyrosinase were produced, and decorated either by curcumin or albumin (BSA) to produce SD/curcumin or SD/BSA NPs as drug delivery vehicles, respectively. Both drug loaded NPs were further blended into SF solutions to produce SD films, as a depot-based drug delivery. The reaction mechanisms for producing new SD NPs were proposed. Anti-oxidative activities for SD NPs were examined by H2O2 scavenge capacities of NPs. NPs were not cytotoxic at concentration of 1000µg/mL. Moreover, heparin was coated to SD films to produce SDH films for temporary implants. Cumulative release profiles for drugs loaded SDH films showed fast releases and then sustained releases stages. Furthermore, the releases of curcumin in sustained stages for varying SD/curcumin NPs loaded into SDH films were dependent on amounts of NPs. BSA releases profiles for SD/BSA NPs loaded into SDH films were similar to those profiles for the films carried with SD/curcumin NPs but release periods of BSA were short. Degrees of PTR effects with irradiation of near infrared on the releases of two drugs loaded films were different. Blood clot at wound areas of rats with SDH films implantations was not found for 24 h study.


Assuntos
Albuminas/química , Antioxidantes/farmacologia , Curcumina/administração & dosagem , Dopamina/química , Fibroínas/química , Trombose/terapia , Animais , Antioxidantes/química , Linhagem Celular , Curcumina/química , Curcumina/farmacologia , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Peróxido de Hidrogênio/metabolismo , Masculino , Camundongos , Nanopartículas , Terapia Fototérmica , Ratos , Trombose/metabolismo
6.
J Mater Sci Mater Med ; 32(1): 5, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33471255

RESUMO

Bone is a flexible and electro active tissue that is vulnerable to various traumatic injuries. The self-healing of damaged bone tissue towards reconstruction is limited due to the lack of proper niche compliances. Nevertheless, the classical grafting techniques like autograft/allograft for bone repair pose challenges like bacterial infections and donor-site morbidity with unsatisfactory outcomes. The use of appropriate biomaterial with osteogenic potential can meet these challenges. In this regard, bioactive glass ceramics is widely used as a bone filler or graft material because of its bonding affinity to bone leading towards bone reconstruction applications without the challenge of post implant infections. Hence, the current study is aimed at addressing this potentiality of zinc (Zn) for doped the bioglass at nano-scale advantages for bone tissue repair. Since, Zn has been demonstrated to have not only antibacterial property but also the stimulatory effect on osteoblasts differentiation, mineralization by enhancing the osteogenic genes expression. In view of these, the present study is focused on sol-gel synthesis and pysico-chemical characterization of Zinc-doped bioglass nanoparticles (Zn-nBGC) and also analyzing its biological implications. The surface morphological and physiochemical characterizations using SEM, EDX, FT-IR and XRD analysis has shown the increased surface area of Zn-nBGC particles providing a great platform for biomolecular interaction, cytocompatibility, cell proliferation and osteogenic differentiation. The obtaining hydroxy apatite groups have initiated in vitro mineralization towards osteogenic lineage formation. Zn has not only involved in enhancing cellular actions but also strengthen the ceramic nanoparticles towards antibacterial application. Hence the finding suggests a biomaterial synthesis of better biomaterial for bone tissue engineering application by preventing post-operative bacterial infection.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Cerâmica/química , Nanoestruturas/química , Transição de Fase , Zinco/química , Adsorção , Animais , Antibacterianos/química , Materiais Biocompatíveis , Biofilmes , Cimentos Ósseos , Osso e Ossos/metabolismo , Diferenciação Celular , Proliferação de Células , Durapatita/química , Humanos , Técnicas In Vitro , Teste de Materiais , Nanopartículas Metálicas/química , Camundongos , Camundongos Endogâmicos C3H , Nanotecnologia , Osteoblastos/citologia , Osteogênese , Regeneração , Medicina Regenerativa/métodos , Engenharia Tecidual/métodos , Alicerces Teciduais/química
7.
J Biomater Appl ; 36(1): 140-151, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33050835

RESUMO

This study spots light on combined Wound healing process conjoining blood coagulation, inflammation reduction, proliferation and remodeling of the cells. The objective is to overcome the drawbacks of conventional clinically applied wound dressings such as poor rigidity, porosity, mechanical potency and bactericidal activity. As nosocomial infection is a very common condition at the wound site, bio-adhesive materials with intrinsic antibacterial properties are used in clinical applications. Considering the provenability of Wollastonite [Calcium silicate (CaSiO3)] to regenerate the soft tissues by inducing vascularization and regeneration of fibroblast cells And the antibacterial potentiality of zinc in clinical applications, the present study focuses on synthesis of Zn-Ws particles and evaluation of its antimicrobial and wound healing potentialities towards skin tissue engineering applications. The compositional characterization by EDAS and FT-IR spectral analysis have substantiated the presence of major elements and corresponding band stretching associated with the synthesized particles whereas the particles morphology by SEM images have shown the size of the Ws and Zn-Ws to be 370 nm and 530 nm respectively. From the in vitro studies, skin regenerative potential of Zn-Ws was determined on promoting fibroblast cell (NIH3T3) proliferation by providing better adhesiveness, biocompatibility and cytocompatibility. The antibacterial property of Zn-Ws evaluation by minimum inhibitory concentration (MIC) and zone of inhibition (ZOI) methods against clinical isolates of Gram +Ve and Gram -Ve bacterial strains have confirmed that the addition of Zn has diminished the bacterial growth and also helped in degrading the bacterial biofilms. Thus it is summed up that the process of wound healing is expected to occur with reduced risk of post-injury infections by the presence of zinc-doping on wollastonite for skin tissue application.


Assuntos
Materiais Biocompatíveis/farmacologia , Compostos de Cálcio/farmacologia , Regeneração/efeitos dos fármacos , Silicatos/farmacologia , Animais , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Fibroblastos , Teste de Materiais , Camundongos , Testes de Sensibilidade Microbiana , Células NIH 3T3 , Porosidade , Pele , Espectroscopia de Infravermelho com Transformada de Fourier , Engenharia Tecidual/métodos , Cicatrização/efeitos dos fármacos , Infecção dos Ferimentos , Zinco
8.
Adv Exp Med Biol ; 1250: 125-140, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32601942

RESUMO

In the tissue engineering research field, nanobiomaterials highlight the impact of novel bioactive materials in both current applications and their potentials in future progress for tissue engineering and regenerative medicine. Tissue engineering is a well-investigated and challenging biomedical field, with promising perspectives to improve and support quality of life for the patient. To assess the response of those extracellular matrices (ECMs), induced by biomedical materials, this review will focus on cell response to natural biomaterials for biocompatibility.


Assuntos
Materiais Biocompatíveis , Engenharia Tecidual , Materiais Biocompatíveis/normas , Células/imunologia , Matriz Extracelular/imunologia , Humanos , Qualidade de Vida , Medicina Regenerativa , Engenharia Tecidual/métodos
9.
Materials (Basel) ; 13(12)2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32560556

RESUMO

Silk fibroin (SF) and hyaluronic acid (HA) were crosslinked by horseradish peroxidase (HRP)/H2O2, and 1,4-Butanediol di-glycidyl ether (BDDE), respectively, to produce HA/SF-IPN (interpenetration network) (HS-IPN) hydrogels. HS-IPN hydrogels consisted of a SF strain with a high content of tyrosine (e.g., strain A) increased viscoelastic modules compared with those with low contents (e.g., strain B and C). Increasing the quantities of SF in HS-IPN hydrogels (e.g., HS7-IPN hydrogels with weight ratio of HA/SF, 5:7) increased viscoelastic modules of the hydrogels. In addition, the mean pores size of scaffolds of the model hydrogels were around 38.96 ± 5.05 µm which was between those of scaffolds H and S hydrogels. Since the viscoelastic modulus of the HS7-IPN hydrogel were similar to those of human nucleus pulposus (NP), it was chosen as the model hydrogel for examining the differentiation of human bone marrow-derived mesenchymal stem cell (hBMSC) to NP. The differentiation of hBMSC induced by transforming growth factor ß3 (TGF-ß3) in the model hydrogels to NP cells for 7 d significantly enhanced the expressions of glycosaminoglycan (GAG) and collagen type II, and gene expressions of aggrecan and collagen type II while decreased collagen type I compared with those in cultural wells. In summary, the model hydrogels consisted of SF of strain A, and high concentrations of SF showed the highest viscoelastic modulus than those of others produced in this study, and the model hydrogels promoted the differentiation of hBMSC to NP cells.

10.
Sensors (Basel) ; 20(2)2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31936424

RESUMO

A silk fibroin composite film that can simultaneously scavenge and probe H2O2 in situ was developed for possibly examining local concentrations of H2O2 for biomedical applications. A multi-functional composite film (GDES) that consists of graphene oxide (G), a photothermally responsive element that was blended with polydopamine (PDA, D)/horseradish peroxidase (HRP, E) (or DE complex), and then GDE microaggregates were coated with silk fibroin (SF, S), a tyrosine-containing protein. At 37 °C, the H2O2-scavenging ability of a GDES film in solution at approximately 7.5 × 10-3 µmol H2O2/mg film was the highest compared with those of S and GS films. The intensities of UV-excitable blue fluorescence of a GDES film linearly increased with increasing H2O2 concentrations from 4.0 µM to 80 µM at 37 °C. Interestingly, after a GDES film scavenged H2O2, the UV-excitable blue fluorescent film could be qualitatively monitored by eye, making the film an eye-probe H2O2 sensor. A GDES film enabled to heat H2O2-containing samples to 37 °C or higher by the absorption of near-IR irradiation at 808 nm. The good biocompatibility of a GDES film was examined according to the requirements of ISO-10993-5. Accordingly, a GDES film was developed herein to scavenge and eye-probe H2O2 in situ and so it has potential for biomedical applications.

11.
Int J Nanomedicine ; 14: 4767-4780, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31308657

RESUMO

BACKGROUND: Magnetic nanoparticles (MNPs) can be localized against hemodynamic forces in blood vessels with the application of an external magnetic field. In addition, PEGylation of nanoparticles may increase the half-life of nanocomposites in circulation. In this work, we examined the effect of PEGylation on the magnetic capture of MNPs in vivo. METHODS: Laser speckle contrast imaging and capillaroscopy were used to assess the magnetic capture of dextran-coated MNPs and red blood cell (RBC) flow in cremaster microvessels of anesthetized rats. Magnetic capture of MNPs in serum flow was visualized with an in vitro circulating system. The effect of PEGylation on MNP-endothelial cell interaction was studied in cultured cells using an iron assay. RESULTS: In microcirculation through cremaster muscle, magnet-induced retention of 250 nm MNPs was associated with a variable reduction in RBC flow, suggesting a dynamic coupling of hemodynamic and magnetic forces. After magnet removal, faster restoration of flow was observed in PEG(+) than PEG(-) group, which may be attributed to a reduced interaction with vascular endothelium. However, PEGylation appears to be required for magnetic capture of 50 nm MNPs in microvessels, which was associated with increased hydrodynamic diameter to 130±6 nm in serum, but independent of the ς-potential. CONCLUSION: These results suggest that PEGylation may enhance magnetic capture of smaller MNPs and dispersion of larger MNPs after magnet removal, which may potentially affect the targeting, pharmacokinetics and therapeutic efficacy.


Assuntos
Dextranos/química , Nanopartículas de Magnetita/química , Microcirculação/fisiologia , Polietilenoglicóis/química , Animais , Hemodinâmica , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Campos Magnéticos , Microvasos/fisiologia , Ratos Sprague-Dawley , Eletricidade Estática
12.
Int J Nanomedicine ; 14: 1533-1549, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30880963

RESUMO

BACKGROUND: Ischemia/reperfusion (I/R) injury causes the generation of many ROS such as H2O2 and leads to vascular thrombosis, which causes tissue damage. PURPOSE: In this investigation, poly (lactideco-glycolide) (PLGA)-based nanoparticles are used for their anticoagulant and antioxidant properties in vascular therapy. METHODS: Both heparin and glutathione are entrapped on PLGA-stearylamine nanoparticles by layer-by-layer interactions. RESULTS: The drug release rate is successfully controlled with only 10.3% of the heparin released after 96 hours. An H2O2-responsive platform is also developed by combining silk fibroin and horse peroxidase to detect H2O2 in this drug delivery system. Besides, hyaluronic acid was decorated on the surface of nanoparticles to target the human bone marrow mesenchymal stem cells (hBMSCs) for cell therapy. The results of an in vitro study indicate that the nanoparticles could be taken up by hBMSCs within 2 hours and exocytosis occurred 6 hours after cellular uptake. CONCLUSION: We propose that the multifunctional nanoparticles that are formed herein can be effectively delivered to the site of an I/R injury via the hBMSC homing effect. The proposed approach can potentially be used to treat vascular diseases, providing a platform for hBMSCs for the controlled delivery of a wide range of drugs.


Assuntos
Anticoagulantes/farmacologia , Antioxidantes/farmacologia , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Aminas/química , Animais , Hipóxia Celular/efeitos dos fármacos , Linhagem Celular , Preparações de Ação Retardada/farmacologia , Liberação Controlada de Fármacos , Glutationa/química , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Ácido Hialurônico/química , Peróxido de Hidrogênio/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Camundongos , Nanopartículas/ultraestrutura , Superóxidos/metabolismo
13.
J Tissue Eng Regen Med ; 12(4): e1852-e1864, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29160940

RESUMO

The effects of the stiffness of substrates on the cell behaviours of human bone marrow-derived mesenchymal stem cells (hBMSC) have been investigated, but the effects of the secondary structures of proteins in the substrates on the morphological transformation and differentiation of hBMSC have yet been elucidated. To investigate these issues, silk fibroin-poly(ε-caprolactone) SP cardiac patches of poly(ε-caprolactone; P), on which is grafted by silk fibroin (SF) with various ß-sheet contents (or crystallinity) to provide various degrees of stiffness, were produced to examine the in vitro behaviours of hBMSC during proliferation, and cardiomyogenesis on the SP patches. ß-sheet contents of SF from 20% to 44% (SP20 to SP44, respectively) were induced on patches, which were examined by attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy, and analysed using the Fourier self-deconvolution method. The stiffness of the SP patches, quantified by their Young's moduli and elasticities, increased with the crystallinity of the SF. During 3 days of proliferation, hBMSC migrated and morphologically transformed into 3D microtissues with diameters of approximately 150-200 µm on low-stiffness SP20 and SP30 patches, whereas 2D monolayers were observed on the SP37 and SP44 patches. The 3D microtissues/patch yielded more extensive in vitro cardiomyogenesis of hBMSC than the 2D cell monolayer with significantly higher expressions of all examined cardiac-specific proteins after induction by 5-aza. Notably, in vivo subcutaneously growing 3D microtissues on SP20 patches and a 2D monolayer on SP44 patches were preliminarily demonstrated in a rat model. Morphological transformations of hBMSC from a 2D monolayer to a 3D microtissue by low-stiffness SP cardiac patches, promoting cardiomyogenesis, provide a new opportunity for cardiac tissue engineering.


Assuntos
Células da Medula Óssea/metabolismo , Diferenciação Celular , Células-Tronco Mesenquimais/metabolismo , Desenvolvimento Muscular , Miócitos Cardíacos/metabolismo , Células da Medula Óssea/citologia , Caproatos/química , Fibroínas/química , Humanos , Lactonas/química , Células-Tronco Mesenquimais/citologia , Miócitos Cardíacos/citologia , Nanofibras/química , Alicerces Teciduais/química
14.
Biomater Sci ; 5(10): 1976-1987, 2017 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-28832034

RESUMO

Cardiovascular disease (CVD), leading to myocardial infarction and heart failure, is one of the major causes of death worldwide. The physiological system cannot significantly regenerate the capabilities of a damaged heart. The current treatment involves pharmacological and surgical interventions; however, less invasive and more cost-effective approaches are sought. Such new approaches are developed to induce tissue regeneration following injury. Hence, regenerative medicine plays a key role in treating CVD. Recently, the extrinsic stimulation of cardiac regeneration has involved the use of potential polymers to stimulate stem cells toward the differentiation of cardiomyocytes as a new therapeutic intervention in cardiac tissue engineering (CTE). The therapeutic potentiality of natural or synthetic polymers and cell surface interactive factors/polymer surface modifications for cardiac repair has been demonstrated in vitro and in vivo. This review will discuss the recent advances in CTE using polymers and cell surface interactive factors that interact strongly with stem cells to trigger the molecular aspects of the differentiation or formulation of cardiomyocytes for the functional repair of heart injuries or cardiac defects.


Assuntos
Miocárdio/citologia , Polímeros/química , Polímeros/farmacologia , Engenharia Tecidual , Animais , Humanos , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Propriedades de Superfície
15.
Biomed Res Int ; 2017: 4051763, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28127555

RESUMO

Micelles, with the structure of amphiphilic molecules including a hydrophilic head and a hydrophobic tail, are recently developed as nanocarriers for the delivery of drugs with poor solubility. In addition, micelles have shown many advantages, such as enhanced permeation and retention (EPR) effects, prolonged circulation times, and increased endocytosis through surface modification. In this study, we measured the critical micelle concentrations, diameters, stability, and cytotoxicity and the cell uptake of micelles against hepatic cells with two kinds of hydrophilic materials: PEG-PCL and HA-g-PCL. We used 131I as a radioactive tracer to evaluate the stability, drug delivery, and cell uptake activity of the micelles. The results showed that HA-g-PCL micelles exhibited higher drug encapsulation efficiency and stability in aqueous solutions. In addition, the 131I-lipiodol loaded HA-g-PCL micelles had better affinity and higher cytotoxicity compared to HepG2 cells.


Assuntos
Sistemas de Liberação de Medicamentos , Óleo Etiodado/administração & dosagem , Radioisótopos do Iodo/administração & dosagem , Compostos Radiofarmacêuticos/administração & dosagem , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Meios de Contraste/administração & dosagem , Meios de Contraste/farmacocinética , Meios de Contraste/toxicidade , Portadores de Fármacos/química , Estabilidade de Medicamentos , Óleo Etiodado/farmacocinética , Óleo Etiodado/toxicidade , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/efeitos da radiação , Humanos , Ácido Hialurônico/análogos & derivados , Interações Hidrofóbicas e Hidrofílicas , Radioisótopos do Iodo/farmacocinética , Radioisótopos do Iodo/toxicidade , Micelas , Tamanho da Partícula , Poliésteres , Compostos Radiofarmacêuticos/farmacocinética , Compostos Radiofarmacêuticos/toxicidade , Solubilidade
16.
Macromol Biosci ; 17(3)2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27678265

RESUMO

Bone marrow-derived mesenchymal stem cell microtissues (BMSCMT) enhanced cardiomyogenesis in vitro and cardiac repairs of myocardial infarcted hearts in vivo are documented. Producing human BMSCMT onto patches in vitro for cardiac tissue engineering has not been reported. For possibly producing human bone marrow-derived mesenchymal stem cell microtissues (hBMSCMT) on an elastic silk fibroin (SF)-poly(ε-caprolactone) (PCL) based patches is hereby designed. After an elastic SF-PCL (SP) patch is fabricated, hyaluronic acid (HA)/SF-PCL(HSP) and HA-GRGD/SF-PCL(HGSP) patches are fabricated by photochemically grafting HA and HA-GRGD onto SP surfaces. The results show that the proliferations of hBMSC on HGSP patches significantly exceed those on the other patches, as determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay. Notably, the formation of 5-aza inducing cardiomyogenic differentiations of hBMSCMT/HGSP patches is observed with typical sizes of ≈317 µm wide and 26 µm high. The cardiomyogenesis of hBMSCMT/HGSP patches including the expressions of cardiac-specific genes (e.g., Gata4) and proteins (e.g., connexin43 (CX43)) significantly exceeds those of hBMSC monolayer on the HSP and SP patches. Promoting in vitro cardiomyogenesis of hBMSC with forming cardiomyogenic differentiation of hBMSCMT/HGSP hybrid patch is possibly mediated by the synergistic functions of HA-GRGD on enhancing the activity of F-actin. The hBMSCMT/HGSP cardiac patch may be further employed to cardiac tissue engineering.


Assuntos
Diferenciação Celular/genética , Células-Tronco Mesenquimais/citologia , Miócitos Cardíacos/citologia , Engenharia Tecidual , Actinas/metabolismo , Materiais Biocompatíveis , Células da Medula Óssea/citologia , Caproatos/química , Proliferação de Células/genética , Fibroínas/química , Humanos , Ácido Hialurônico/química , Lactonas/química , Infarto do Miocárdio/patologia , Infarto do Miocárdio/terapia , Seda/química , Sais de Tetrazólio/química , Tiazóis/química , Técnicas de Cultura de Tecidos , Alicerces Teciduais
17.
Biomed Res Int ; 2016: 1917394, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28053978

RESUMO

The microenvironment of neuron cells plays a crucial role in regulating neural development and regeneration. Hyaluronic acid (HA) biomaterial has been applied in a wide range of medical and biological fields and plays important roles in neural regeneration. PC12 cells have been reported to be capable of endogenous NGF synthesis and secretion. The purpose of this research was to assess the effect of HA biomaterial combining with PC12 cells conditioned media (PC12 CM) in neural regeneration. Using SH-SY5Y cells as an experimental model, we found that supporting with PC12 CM enhanced HA function in SH-SY5Y cell proliferation and adhesion. Through RP-nano-UPLC-ESI-MS/MS analyses, we identified increased expression of HSP60 and RanBP2 in SH-SY5Y cells grown on HA-modified surface with cotreatment of PC12 CM. Moreover, we also identified factors that were secreted from PC12 cells and may promote SH-SY5Y cell proliferation and adhesion. Here, we proposed a biomaterial surface enriched with neurotrophic factors for nerve regeneration application.


Assuntos
Adesão Celular/efeitos dos fármacos , Ácido Hialurônico/administração & dosagem , Neuroblastoma/metabolismo , Engenharia Tecidual , Animais , Proliferação de Células/efeitos dos fármacos , Microambiente Celular/efeitos dos fármacos , Chaperonina 60/biossíntese , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Humanos , Proteínas Mitocondriais/biossíntese , Chaperonas Moleculares/biossíntese , Regeneração Nervosa/genética , Neuroblastoma/tratamento farmacológico , Neuroblastoma/patologia , Neurônios/metabolismo , Neurônios/fisiologia , Complexo de Proteínas Formadoras de Poros Nucleares/biossíntese , Células PC12 , Ratos
18.
Int J Mol Sci ; 16(1): 1657-76, 2015 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-25588218

RESUMO

Silk fibroin (SF) is a protein with bulky hydrophobic domains and can be easily purified as sericin-free silk-based biomaterial. Silk fibroin modified chitosan nanoparticle (SF-CSNP), a biocompatible material, has been widely used as a potential drug delivery system. Our current investigation studied the bio-effects of the SF-CSNP uptake by liver cells. In this experiment, the characterizations of SF-CSNPs were measured by particle size analysis and protein assay. The average size of the SF-CSNP was 311.9 ± 10.7 nm, and the average zeta potential was +13.33 ± 0.3 mV. The SF coating on the SF-CSNP was 6.27 ± 0.17 µg/mL. Moreover, using proteomic approaches, several proteins involved in the ubiquitin proteasome pathway were identified by analysis of differential protein expressions of HepG2 cell uptake the SF-CSNP. Our experimental results have demonstrated that the SF-CSNP may be involved in liver cancer cell survival and proliferation.


Assuntos
Quitosana/metabolismo , Portadores de Fármacos/metabolismo , Fibroínas/metabolismo , Nanopartículas/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Ubiquitina/metabolismo , Materiais Biocompatíveis/metabolismo , Linhagem Celular , Células Hep G2 , Humanos , Proteômica , Transdução de Sinais
19.
Biomed Res Int ; 2014: 209469, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24818131

RESUMO

The purpose of this study was to develop the pathway of silk fibroin (SF) biopolymer surface induced cell membrane protein activation. Fibroblasts were used as an experimental model to evaluate the responses of cellular proteins induced by biopolymer material using a mass spectrometry-based profiling system. The surface was covered by multiwalled carbon nanotubes (CNTs) and SF to increase the surface area, enhance the adhesion of biopolymer, and promote the rate of cell proliferation. The amount of adhered fibroblasts on CNTs/SF electrodes of quartz crystal microbalance (QCM) greatly exceeded those on other surfaces. Moreover, analyzing differential protein expressions of adhered fibroblasts on the biopolymer surface by proteomic approaches indicated that CD44 may be a key protein. Through this study, utilization of mass spectrometry-based proteomics in evaluation of cell adhesion on biopolymer was proposed.


Assuntos
Materiais Biocompatíveis/farmacologia , Fibroínas/farmacologia , Proteínas/metabolismo , Proteômica , Animais , Bromodesoxiuridina/metabolismo , Adesão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Eletrodos , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Ontologia Genética , Receptores de Hialuronatos/metabolismo , Imuno-Histoquímica , Espectrometria de Massas , Microscopia de Força Atômica , Nanotubos de Carbono/química , Técnicas de Microbalança de Cristal de Quartzo , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície
20.
Biomed Res Int ; 2014: 789591, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24757677

RESUMO

Chitosan nanoparticle, a biocompatible material, was used as a potential drug delivery system widely. Our current investigation studies were the bioeffects of the chitosan nanoparticle uptake by liver cells. In this experiment, the characterizations of chitosan nanoparticles were measured by transmission electron microscopy and particle size analyzer. The average size of the chitosan nanoparticle was 224.6 ± 11.2 nm, and the average zeta potential was +14.08 ± 0.7 mV. Moreover, using proteomic approaches to analyze the differential protein expression patterns resulted from the chitosan nanoparticle uptaken by HepG2 and CCL-13 cells identified several proteins involved in the PI3K/AKT1/mTOR pathway. Our experimental results have demonstrated that the chitosan nanoparticle may involve in the liver cancer cell metastasis and proliferation.


Assuntos
Proliferação de Células/efeitos dos fármacos , Quitosana/farmacologia , Neoplasias Hepáticas/metabolismo , Fígado/metabolismo , Nanopartículas , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Quitosana/química , Células Hep G2 , Humanos , Fígado/patologia , Neoplasias Hepáticas/patologia , Metástase Neoplásica , Proteômica/métodos
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