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1.
Addict Biol ; 28(1): e13253, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36577735

RESUMO

Use of prescription opioids, particularly oxycodone, is an initiating factor driving the current opioid epidemic. There are several challenges with modelling oxycodone abuse. First, prescription opioids including oxycodone are orally self-administered and have different pharmacokinetics and dynamics than morphine or fentanyl, which have been more commonly used in rodent research. This oral route of administration determines the pharmacokinetic profile, which then influences the establishment of drug-reinforcement associations in animals. Moreover, the pattern of intake and the environment in which addictive drugs are self-administered are critical determinants of the levels of drug intake, of behavioural sensitization and of propensity to relapse behaviour. These are all important considerations when modelling prescription opioid use, which is characterized by continuous drug access in familiar environments. Thus, to model features of prescription opioid use and the transition to abuse, we designed an oral, homecage-based oxycodone self-administration paradigm. Mice voluntarily self-administer oxycodone in this paradigm without any taste modification such as sweeteners, and the majority exhibit preference for oxycodone, escalation of intake, physical signs of dependence and reinstatement of seeking after withdrawal. In addition, a subset of animals demonstrate drug taking that is resistant to aversive consequences. This model is therefore translationally relevant and useful for studying the neurobiological substrates of prescription opioid abuse.


Assuntos
Transtornos Relacionados ao Uso de Opioides , Oxicodona , Masculino , Camundongos , Feminino , Animais , Analgésicos Opioides/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Fentanila , Reforço Psicológico
2.
J Surg Res ; 264: 90-98, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33794389

RESUMO

BACKGROUND: The Slit-Robo pathway is a key regulator of angiogenesis and cellular function in experimental models. Slit3 proteins exhibit both proangiogenic and antiangiogenic properties, but the exact mechanism remains unclear. It is theorized that Slit3 may be a potential treatment for vascular diseases and cancer. METHODS: Slit3 labeled with I-125 was encapsulated in microbeads composed of low-viscosity alginate of high-glucuronic acid content, first coated with poly-L-ornithine for various durations and finally with low-viscosity high mannuronic acid. Gamma counter was used to measure microbead encapsulation efficiency and Slit3 release. Markers of angiogenesis were assessed with Boyden chamber, scratch wound, and Matrigel tube formation assays using human umbilical vein and mouse endothelial cells. RESULTS: On incubation of Slit3-loaded microbeads, there was an initial burst phase release of Slit3 for the first 24 h followed by sustained release for 6 to 12 d. Microbead composition determined encapsulation efficiency and rate of release; Slit3 encapsulation was most efficient in microbeads with lower low-viscosity alginate of high-glucuronic acid content concentrations (1.5%) and no poly-L-ornithine coating. Compared with controls (media alone), Slit3 microbeads significantly inhibited in vitro cellular migration, endothelial cell migration for wound closure at 24 and 48 h and endothelial tube formation (P < 0.001, respectively). CONCLUSIONS: Slit3 can be effectively encapsulated and delivered via a controlled release pattern using alginate microbeads. Microbead encapsulation reduces in vitro endothelial tube formation and inhibits cellular migration to impair angiogenesis. Thus, Slit3 microparticles may be explored as a therapeutic option to mitigate tumor proliferation.


Assuntos
Alginatos/química , Portadores de Fármacos/química , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Proteínas de Membrana/administração & dosagem , Neovascularização Patológica/tratamento farmacológico , Animais , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Proteínas de Membrana/farmacocinética , Camundongos , Microesferas , Neoplasias/irrigação sanguínea , Neoplasias/tratamento farmacológico , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacocinética
4.
Methods Mol Biol ; 1479: 157-171, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27738934

RESUMO

Microencapsulation of islets is a procedure used to immunoisolate islets in order to obviate the need for immunosuppression of islet transplant recipients. Although microencapsulated islets have routinely been transplanted in the peritoneal cavity, the ideal site for their engraftment remains to be determined. The omentum, a highly vascularized tissue, has been proposed as an alternative site for microencapsulated islet transplantation. An added benefit to the omentum is that implanted microcapsules can be easily retrieved for post-transplant evaluation. This chapter describes a collagenase-based procedure for the retrieval of microencapsulated islets following the harvest of omentum pouch site of transplantation.


Assuntos
Células Imobilizadas/citologia , Diabetes Mellitus Experimental/terapia , Transplante das Ilhotas Pancreáticas/métodos , Ilhotas Pancreáticas/citologia , Omento/cirurgia , Alginatos/química , Animais , Cápsulas/química , Sobrevivência Celular , Células Imobilizadas/metabolismo , Células Imobilizadas/transplante , Composição de Medicamentos , Sobrevivência de Enxerto , Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , Camundongos , Ratos
5.
Pancreas ; 43(4): 605-13, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24681880

RESUMO

OBJECTIVE: Our study aim was to determine encapsulated islet graft viability in an omentum pouch and the effect of fibroblast growth factor 1 (FGF-1) released from our redesigned alginate microcapsules on the function of the graft. METHODS: Isolated rat islets were encapsulated in an inner core made with 1.5% low-viscosity-high-mannuronic-acid alginate followed by an external layer made with 1.25% low-viscosity high-guluronic acid alginate with or without FGF-1, in microcapsules measuring 300 to 400 µm in diameter. The 2 alginate layers were separated by a perm-selective membrane made with 0.1% poly-L-ornithine, and the inner low-viscosity-high-mannuronic-acid core was partially chelated using 55 mM sodium citrate for 2 minutes. RESULTS: A marginal mass of encapsulated islet allografts (∼2000 islets/kg) in streptozotocin-diabetic Lewis rats caused significant reduction in blood glucose levels similar to the effect observed with encapsulated islet isografts. Transplantation of alloislets coencapsulated with FGF-1 did not result in better glycemic control, but induced greater body weight maintenance in transplant recipients compared with those that received only alloislets. Histological examination of the retrieved tissue demonstrated morphologically and functionally intact islets in the microcapsules, with no signs of fibrosis. CONCLUSIONS: We conclude that the omentum is a viable site for encapsulated islet transplantation.


Assuntos
Alginatos , Diabetes Mellitus Experimental/cirurgia , Sobrevivência de Enxerto , Imunocompetência , Transplante das Ilhotas Pancreáticas/métodos , Ilhotas Pancreáticas/metabolismo , Omento/cirurgia , Alicerces Teciduais , Indutores da Angiogênese/administração & dosagem , Animais , Glicemia/metabolismo , Sobrevivência Celular , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/imunologia , Fator 1 de Crescimento de Fibroblastos/administração & dosagem , Ácido Glucurônico , Ácidos Hexurônicos , Ilhotas Pancreáticas/irrigação sanguínea , Ilhotas Pancreáticas/imunologia , Masculino , Neovascularização Fisiológica , Omento/irrigação sanguínea , Ratos Endogâmicos Lew , Ratos Wistar , Fatores de Tempo
6.
Interface Focus ; 4(1): 20130050, 2014 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-24501678

RESUMO

It has been established that nerves and skeletal muscles respond and communicate via electrical signals. In regenerative medicine, there is current emphasis on using conductive nanomaterials to enhance electrical conduction through tissue-engineered scaffolds to increase cell differentiation and tissue regeneration. We investigated the role of chemically synthesized polyaniline (PANI) and poly(3,4-ethylenedioxythiophene) (PEDOT) conductive polymer nanofibres for conductive gels. To mimic a naturally derived extracellular matrix for cell growth, type I collagen gels were reconstituted with conductive polymer nanofibres and cells. Cell viability and proliferation of PC-12 cells and human skeletal muscle cells on these three-dimensional conductive collagen gels were evaluated in vitro. PANI and PEDOT nanofibres were found to be cytocompatible with both cell types and the best results (i.e. cell growth and gel electrical conductivity) were obtained with a low concentration (0.5 wt%) of PANI. After 7 days of culture in the conductive gels, the densities of both cell types were similar and comparable to collagen positive controls. Moreover, PC-12 cells were found to differentiate in the conductive hydrogels without the addition of nerve growth factor or electrical stimulation better than collagen control. Importantly, electrical conductivity of the three-dimensional gel scaffolds increased by more than 400% compared with control. The increased conductivity and injectability of the cell-laden collagen gels to injury sites in order to create an electrically conductive extracellular matrix makes these biomaterials very conducive for the regeneration of tissues.

7.
J Urol ; 191(3): 850-9, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23973520

RESUMO

PURPOSE: Cellular therapy induced transient urodynamic improvement in a rat model of Parkinson disease in which bladder dysfunction was noted after unilateral injection of 6-hydroxydopamine into the medial forebrain bundle. We sought to prolong the effect by injecting allogeneic rat bone marrow mesenchymal stromal cells before and after microencapsulation into the substantia nigra pars compacta. MATERIALS AND METHODS: Female rats underwent unilateral stereotactic injection of 6-hydroxydopamine in the medial forebrain bundle. Injection was performed in the ipsilateral substantia nigra pars compacta using vehicle alone or vehicle with nonmicroencapsulated or microencapsulated rat bone marrow derived mesenchymal stromal cells. Rats were evaluated by cystometry 7, 14, 28 and 42 days after treatment. Brains were extracted for immunostaining. RESULTS: At 42 days the nonmicroencapsulated group had lower threshold and intermicturition pressure, spontaneous activity and AUC than vehicle treated animals. Rats that received microencapsulated cells had lower threshold pressure at 28 days and lower spontaneous activity at 42 days than vehicle treated rats. Microencapsulated and nonmicroencapsulated rat bone marrow derived mesenchymal stromal cells were noted in the substantia nigra pars compacta up to 42 days after transplantation. At 42 days tyrosine hydroxylase positive neurons were more numerous in the substantia nigra pars compacta of the nonmicroencapsulated group, followed by the microencapsulated and vehicle treated groups. CONCLUSIONS: Urodynamic effects of the 6-hydroxydopamine lesion persisted up to 42 days after vehicle injection. Transplantation of nonmicroencapsulated rat bone marrow derived mesenchymal stromal cells improved urodynamic pressure by 42 days after treatment more markedly than microencapsulated cells. This was associated with more tyrosine hydroxylase positive neurons in the treated substantia nigra pars compacta of the nonmicroencapsulated group, suggesting that functional improvement requires a juxtacrine effect.


Assuntos
Medula Óssea/fisiopatologia , Terapia Baseada em Transplante de Células e Tecidos , Transplante de Células-Tronco Mesenquimais , Doença de Parkinson/fisiopatologia , Doença de Parkinson/terapia , Urodinâmica , Animais , Modelos Animais de Doenças , Feminino , Citometria de Fluxo , Imuno-Histoquímica , Microscopia Confocal , Oxidopamina , Ratos , Ratos Sprague-Dawley , Substância Negra/fisiopatologia
8.
Pathobiology ; 80(4): 194-202, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23652283

RESUMO

Islet transplantation has been shown to be a viable treatment option for patients afflicted with type 1 diabetes. However, the lack of availablity of human pancreases and the need to use risky immunosuppressive drugs to prevent transplant rejection remain two major obstacles to the routine use of islet transplantation in diabetic patients. Successful development of a bioartificial pancreas using the approach of microencapsulation with perm-selective coating of islets in hydrogels for graft immunoisolation holds tremendous promise for diabetic patients because it has great potential to overcome these two barriers. In this review article, we will discuss the need for a bioartificial pancreas, provide a detailed description of the microencapsulation process, and review the status of the technology in clinical development. We will also critically review the various factors that will need to be taken into consideration in order to achieve the ultimate goal of routine clinical application.


Assuntos
Diabetes Mellitus Tipo 1/terapia , Composição de Medicamentos/métodos , Pâncreas Artificial , Pâncreas/fisiologia , Alginatos/química , Ácido Glucurônico/química , Rejeição de Enxerto/prevenção & controle , Ácidos Hexurônicos/química , Humanos , Transplante das Ilhotas Pancreáticas
9.
Biomaterials ; 34(22): 5488-95, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23583038

RESUMO

Emergent technologies of regenerative medicine have the potential to overcome the limitations of organ transplantation by supplying tissues and organs bioengineered in the laboratory. Pancreas bioengineering requires a scaffold that approximates the biochemical, spatial and vascular relationships of the native extracellular matrix (ECM). We describe the generation of a whole organ, three-dimensional pancreas scaffold using acellular porcine pancreas. Imaging studies confirm that our protocol effectively removes cellular material while preserving ECM proteins and the native vascular tree. The scaffold was seeded with human stem cells and porcine pancreatic islets, demonstrating that the decellularized pancreas can support cellular adhesion and maintenance of cell functions. These findings advance the field of regenerative medicine towards the development of a fully functional, bioengineered pancreas capable of establishing and sustaining euglycemia and may be used for transplantation to cure diabetes mellitus.


Assuntos
Bioengenharia/métodos , Matriz Extracelular/metabolismo , Ilhotas Pancreáticas/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Detergentes/farmacologia , Matriz Extracelular/efeitos dos fármacos , Humanos , Ilhotas Pancreáticas/irrigação sanguínea , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/ultraestrutura , Perfusão , Sus scrofa
10.
Biomaterials ; 34(4): 1311-26, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23137393

RESUMO

To provide site-specific delivery and targeted release of growth factors to implanted urine-derived stem cells (USCs), we prepared microbeads of alginate containing growth factors. The growth factors included VEGF, IGF-1, FGF-1, PDGF, HGF and NGF. Radiolabeled growth factors were loaded separately and used to access the in vitro release from the microbeads with a gamma counter over 4 weeks. In vitro endothelial differentiation of USCs by the released VEGF from the microbeads in a separate experiment confirmed that the released growth factors from the microbeads were bioactive. USCs and microbeads were mixed with the collagen gel type 1 (2 mg/ml) and used for in vivo studies through subcutaneous injection into nude mice. Four weeks after subcutaneous injection, we found that grafted cell survival was improved and more cells expressed myogenic and endothelial cell transcripts and markers compared to controls. More vessel formation and innervations were observed in USCs combined with six growth factors cocktail incorporated in microbeads compared to controls. In conclusion, a combination of growth factors released locally from the alginate microbeads induced USCs to differentiate into a myogenic lineage, enhanced revascularization and innervation, and stimulated resident cell growth in vivo. This approach could potentially be used for cell therapy in the treatment of stress urinary incontinence.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Fibras Musculares Esqueléticas/citologia , Fibras Musculares Esqueléticas/fisiologia , Neovascularização Fisiológica/fisiologia , Células-Tronco/citologia , Células-Tronco/fisiologia , Urina/citologia , Adulto , Diferenciação Celular/efeitos dos fármacos , Humanos , Masculino , Microesferas , Fibras Musculares Esqueléticas/efeitos dos fármacos , Nanocápsulas , Neovascularização Fisiológica/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos
11.
Expert Rev Clin Immunol ; 8(7): 685-92, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23078065

RESUMO

Immunoisolation refers to an immunological strategy in which nonself antigens present on an allograft or xenograft are not allowed to come in contact with the host immune system, and it is implemented to prevent allorecognition and avoid immunosuppression. In this setting, the two most promising technologies, encapsulation of pancreatic islets (EPI) and immunocloaking (IC), are used. In the case of EPI, islets are inserted in capsules that, allow exchange of oxygen, nutrients and other molecules. In the case of IC, a natural nanofilm is injected prior to renal transplantation within the vasculature of the graft with the intent to pave the inner surface of the vascular lumen and camouflage the antigens located on the membrane of endothelia cells. Significant progress achieved in experimental models is leading EPI and IC to clinical translation.


Assuntos
Transplante das Ilhotas Pancreáticas , Medicina Regenerativa/métodos , Animais , Cápsulas , Humanos , Terapia de Imunossupressão , Transplante das Ilhotas Pancreáticas/imunologia , Transplante das Ilhotas Pancreáticas/métodos , Transplante de Órgãos/métodos
12.
J Biomed Mater Res A ; 99(4): 586-97, 2011 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-21953843

RESUMO

Infection and inflammation associated with orthopedic implants can be life threatening, time consuming, and expensive, thus, motivating the development of a local drug delivery platform that could prevent such deleterious events. For this purpose, nanostructured polypyrrole (PPy) incorporating antibiotics and anti-inflammatory drugs (penicillin/streptomycin (P/S) or dexamethasone (Dex), respectively) were coated on commercially pure titanium through an easy to use electrochemical deposition method. As shown in our previous study, about 80% (compared with initial amount) of these incorporated drugs were released after electrical stimulation spanning five cycles (voltage was varied between -1 V and 1 V). In a further continuation of this work, nanostructured P/S incorporated PPy coatings on titanium were demonstrated to be bactericidal against Staphylococcus epidermis after 1 h, and when incorporated with Dex, inhibited macrophage (an inflammatory and immune response cell) growth after 8 and 13 h of in vitro culture. Moreover, nanostructured PPy-drug films coated on titanium enhanced osteoblast (bone forming cells) proliferation, while at the same time, suppressed fibroblast (fibrous tissue forming cells) proliferation for up to 5 days. After electrical stimulation, antimicrobial and anti-inflammatory-coated devices yielded lower bacteria colonies and macrophage growth compared with unincorporated-drug PPy films (controls). This study, thus, suggests that drug incorporated nanostructured PPy coatings on titanium are capable of effectively treating potential orthopedic implant infection and inflammation, and lays the foundation for the further development of local and controllable on-demand drug delivery coatings to improve orthopedic implant efficacy.


Assuntos
Materiais Revestidos Biocompatíveis/química , Sistemas de Liberação de Medicamentos , Nanoestruturas , Polímeros/química , Pirróis/química , Titânio/química , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Dexametasona/química , Dexametasona/farmacologia , Estimulação Elétrica , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Humanos , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Teste de Materiais , Camundongos , Células NIH 3T3 , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Penicilinas/química , Penicilinas/farmacologia , Próteses e Implantes/efeitos adversos , Staphylococcus epidermidis/efeitos dos fármacos , Estreptomicina/química , Estreptomicina/farmacologia , Propriedades de Superfície
13.
Nanotechnology ; 22(8): 085101, 2011 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-21242621

RESUMO

Previous studies have demonstrated that multi-walled carbon nanotubes grown out of anodized nanotubular titanium (MWNT-Ti) can be used as a sensing electrode for various biomedical applications; such sensors detected the redox reactions of certain molecules, specifically proteins deposited by osteoblasts during extracellular matrix bone formation. Since it is known that polypyrrole (PPy) can release drugs upon electrical stimulation, in this study antibiotics (penicillin/streptomycin, P/S) or an anti-inflammatory drug (dexamethasone, Dex), termed PPy[P/S] or PPy[Dex], respectively, were electrodeposited in PPy on titanium. The objective of the present study was to determine if such drugs can be released from PPy on demand and (by applying a voltage) control cellular behavior important for orthopedic applications. Results showed that PPy films possessed nanometer-scale roughness as analyzed by atomic force microscopy. X-ray photoelectron spectroscopy confirmed the presence of P/S and Dex encapsulated within the PPy films. Results from cyclic voltammetry showed that 80% of the drugs were released on demand when sweep voltages were applied for five cycles at a scan rate of 0.1 V s(-1). Furthermore, osteoblast (bone-forming cells) and fibroblast (fibrous tissue-forming cells) adhesion were determined on the PPy films. Results showed that PPy[Dex] enhanced osteoblast adhesion after 4 h of culture compared to plain Ti. PPy-Ti (with or without anionic drug doping) inhibited fibroblast adhesion compared to plain Ti. These in vitro results confirmed that electrodeposited PPy[P/S] and PPy[Dex] can release drugs on demand to potentially fight bacterial infection, reduce inflammation, promote bone growth or reduce fibroblast functions, further implicating the use of such materials as implant sensors.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Galvanoplastia/métodos , Nanoestruturas/química , Polímeros/química , Pirróis/química , Titânio/química , Análise de Variância , Linhagem Celular , Dexametasona/administração & dosagem , Dexametasona/química , Fibroblastos , Humanos , Microscopia de Força Atômica , Microscopia Eletrônica de Transmissão , Nanotubos de Carbono/química , Nanotubos de Carbono/ultraestrutura , Osteoblastos , Oxirredução , Penicilinas/administração & dosagem , Penicilinas/química , Espectroscopia Fotoeletrônica , Análise Espectral Raman , Estreptomicina/administração & dosagem , Estreptomicina/química , Propriedades de Superfície
14.
J Biomed Mater Res A ; 95(1): 129-36, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20540097

RESUMO

Diamond coatings with superior chemical stability, antiwear, and cytocompatibility properties have been considered for lengthening the lifetime of metallic orthopedic implants for over a decade. In this study, an attempt to tailor the surface properties of diamond films on titanium to promote osteoblast (bone forming cell) adhesion was reported. The surface properties investigated here included the size of diamond surface features, topography, wettability, and surface chemistry, all of which were controlled during microwave plasma enhanced chemical-vapor-deposition (MPCVD) processes using CH4-Ar-H2 gas mixtures. The hardness and elastic modulus of the diamond films were also determined. H2 concentration in the plasma was altered to control the crystallinity, grain size, and topography of the diamond coatings, and specific plasma gases (O2 and NH3) were introduced to change the surface chemistry of the diamond coatings. To understand the impact of the altered surface properties on osteoblast responses, cell adhesion tests were performed on the various diamond-coated titanium. The results revealed that nanocrystalline diamond (grain sizes <100 nm) coated titanium dramatically increased surface hardness, and the introduction of O2 and NH3 during the MPCVD process promoted osteoblast adhesion on diamond and, thus, should be further studied for improving orthopedic applications.


Assuntos
Materiais Revestidos Biocompatíveis/farmacologia , Diamante/farmacologia , Teste de Materiais/métodos , Nanopartículas/química , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Titânio/farmacologia , Adesão Celular/efeitos dos fármacos , Módulo de Elasticidade/efeitos dos fármacos , Fluorescência , Dureza/efeitos dos fármacos , Humanos , Microscopia de Força Atômica , Nanopartículas/ultraestrutura , Análise Espectral Raman , Coloração e Rotulagem , Propriedades de Superfície/efeitos dos fármacos , Água/química
15.
Tissue Eng Part C Methods ; 16(6): 1233-43, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20184414

RESUMO

Recently, hydrogels (alginate, agarose, polyethylene glycol, etc.) have been investigated as promising cartilage-healing materials. To further improve cell-material interactions or mechanical properties of such hydrogel scaffolds, many materials (such as ceramics or carbon nanotubes) have been added to produce composites with tailored properties. In this study, rosette nanotubes (RNTs, self-assembled nanotubes built from DNA base pairs), hydrogels, and cells (specifically, fibroblast-like type-B synoviocytes [SFB cells] and chondrocytes) were combined via a novel electrospinning technique to generate three-dimensional implantable scaffolds for cartilage repair. Importantly, results of this study showed that electrospun RNT/hydrogel composites improved both SFB cell and chondrocyte functions. RNT/hydrogel composites promoted SFB cell chondrogenic differentiation in 2 week culture experiments. Further, studies demonstrated that RNTs enhanced hydrogel adhesive strength to severed collagen. Results of this study thus provided a nanostructured scaffold that enhanced SFB cell adhesion, viability, and chondrogenic differentiation compared to nanosmooth hydrogels without RNTs. This study provided an alternative cartilage regenerative material derived from RNTs that could be directly electrospun into cartilage defects (with SFB cells and/or chondrocytes) to bond to severed collagen and promote cell adhesion, viability, and subsequent functions.


Assuntos
Cartilagem/citologia , Hidrogéis/síntese química , Nanotubos/química , Engenharia Tecidual/instrumentação , Alicerces Teciduais/química , Adesividade , Animais , Cartilagem/fisiologia , Técnicas de Cultura de Células , Resinas Compostas/síntese química , Resinas Compostas/química , Galvanoplastia/métodos , Feminino , Fibroblastos/citologia , Fibroblastos/fisiologia , Hidrogéis/química , Teste de Materiais , Modelos Biológicos , Modelos Moleculares , Suínos , Membrana Sinovial/citologia , Membrana Sinovial/fisiologia
16.
J Biomed Mater Res A ; 92(3): 1190-201, 2010 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-19322818

RESUMO

The development of new materials through novel surface modification techniques to enhance orthopedic implant lifetimes (hence, decreasing the need for revision surgery) is of great interest to the medical community. The purpose of this in vitro study was to treat common metallic implant materials [such as titanium (Ti) and a titanium alloy (Ti6Al4V)] and traditional polymeric materials (like polyethylene terephthalate, polyvinyl chloride, polyurethane, polytetrafluoroethylene, ultra-high molecular weight polyethylene (UHMWPE) and nylon) with either nanoparticulate alumina or titanium using novel (i) ionic plasma deposition (IPD) and (ii) nitrogen ion immersion plasma deposition (NIIPD) techniques. The treated surfaces were characterized by scanning electron microscopy, atomic force microscopy and surface energy, demonstrating greater nanoscale roughness on the modified surfaces regardless of the underlying material or coating applied. These surface-modified substrates were also tested for cytocompatibility properties with osteoblasts (or bone-forming cells). Results showed increased osteoblast adhesion on modified compared to control (traditional or untreated) materials. Since the adhesion of osteoblasts is the first crucial step for new bone synthesis, these results are very promising and suggest that the plasma deposition processes used in this study should be further investigated to improve the longevity of orthopedic implants.


Assuntos
Adesão Celular , Metais/química , Nanoestruturas , Osteoblastos/citologia , Polímeros/química , Células Cultivadas , Humanos , Microscopia de Força Atômica , Microscopia Eletrônica de Varredura
17.
Biomed Microdevices ; 12(4): 575-87, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19096767

RESUMO

Future biomaterials must simultaneously enhance tissue regeneration while minimizing immune responses and inhibiting infection. While the field of tissue engineering has promised to develop materials that can promote tissue regeneration for the entire body, such promises have not become reality. However, tissue engineering has experienced great progress due to the recent emergence of nanotechnology. Specifically, it has now been well established that increased tissue regeneration can be achieved on almost any surface by employing novel nano-textured surface features. Numerous studies have reported that nanotechnology accelerates various regenerative therapies, such as those for the bone, vascular, heart, cartilage, bladder and brain tissue. Various nano-structured polymers and metals (alloys) have been investigated for their bio (and cyto) compatibility properties. This review paper discusses several of the latest nanotechnology findings in regenerative medicine (also now called nanomedicine) as well as their relative levels of success.


Assuntos
Nanomedicina/métodos , Medicina Regenerativa/métodos , Animais , Humanos
18.
Acta Biomater ; 5(5): 1425-32, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19264563

RESUMO

Extensive prolonged interactions of inflammatory cells (such as macrophages) at the host-implant interface may lead to implant failure. While previous studies have shown increased in vitro and in vivo bone cell adhesion, proliferation and mineralization on nanophase compared to currently implanted ceramics, few studies have been conducted to elucidate inflammatory cell responses on such nanophase ceramics. Controlling surface feature size and corresponding surface roughness on implants may clearly alter immune cell responses, which would be an extremely important consideration for the use of nanostructured materials as improved biomaterials. In this study, reduced macrophage density was observed on alumina (Al(2)O(3)) compacts with greater nanometer surface roughness accompanied by changes in crystallinity for up to 24 h in culture. Since alumina is a commonly used ceramic in orthopedic applications, this in vitro study continues to support the use of nanophase ceramics as improved orthopedic implants by demonstrating reduced macrophage responses.


Assuntos
Óxido de Alumínio/química , Macrófagos/citologia , Nanopartículas/química , Tamanho da Partícula , Adesão Celular/efeitos dos fármacos , Contagem de Células , Linhagem Celular , Forma Celular/efeitos dos fármacos , Cristalização , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Nanopartículas/ultraestrutura , Propriedades de Superfície/efeitos dos fármacos , Difração de Raios X
19.
Biotechnol Bioeng ; 103(3): 459-71, 2009 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-19241389

RESUMO

Techniques to regenerate the vasculature have risen considerably over the last few decades due to the increased clinical diagnosis of artery narrowing and blood vessel blockage. Although initially re-establishing blood flow, current small diameter vascular regenerative materials often eventually cause thrombosis and restenosis due to a lack of initial endothelial cell coverage on such materials. The objective of this in vitro study was to evaluate commonly used vascular materials (specifically, polyethylene terephthalate, polytetrafluoroethylene, polyvinyl chloride, polyurethane, nylon, commercially pure titanium, and a titanium alloy (Ti6Al4V)) modified using an ionic plasma deposition (IPD) process and a nitrogen ion implantation plasma deposition (NIIPD) process. Such surface modifications have been previously shown to create nanostructured surface features which mimic the natural nanostructured surface features of blood vessels. The modified and unmodified surfaces were characterized by scanning electron microscopy, atomic force microscopy and surface energy measurements. Furthermore, in vitro endothelial cell adhesion tests (a key first step for vascular material endothelialization) demonstrated increased endothelial cell adhesion on many modified (with IPD and NIIPD + IPD) compared to unmodified samples. In general, endothelial cell adhesion increased with nanoroughness and surface energy but demonstrated a decreased endothelial cell adhesion trend after an optimal coating surface energy value was reached. Thus, results from this study provided materials and a versatile surface modification process that can potentially increase endothelialization faster than current unmodified (conventional) polymer and metallic vascular materials.


Assuntos
Prótese Vascular , Adesão Celular , Materiais Revestidos Biocompatíveis , Células Endoteliais/fisiologia , Plasma/fisiologia , Stents , Microscopia de Força Atômica , Microscopia Eletrônica de Varredura , Nanoestruturas/ultraestrutura , Propriedades de Superfície
20.
Int J Nanomedicine ; 3(2): 229-41, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18686782

RESUMO

Previous studies have demonstrated greater functions ofosteoblasts (bone-forming cells) on nanophase compared with conventional metals. Nanophase metals possess a biologically inspired nanostructured surface that mimics the dimensions of constituent components in bone, including collagen and hydroxyapatite. Not only do these components possess dimensions on the nanoscale, they are aligned in a parallel manner creating a defined orientation in bone. To date, research has yet to evaluate the effect that organized nanosurface features can have on the interaction of osteoblasts with material surfaces. Therefore, to determine if surface orientation of features can mediate osteoblast adhesion and morphology, this study investigated osteoblast function on patterned titanium substrates containing alternating regions of micron rough and nano rough surfaces prepared by novel electron beam evaporation techniques. This study was also interested in determining whether or not the size of the patterned regions had an effect on osteoblast behavior and alignment. Results indicated early controlled osteoblast alignment on these patterned materials as well as greater osteoblast adhesion on the nano rough regions of these patterned substrates. Interestingly, decreasing the width of the nano rough regions (from 80 microm to 22 microm) on these patterned substrates resulted in a decreased number of osteoblasts adhering to these areas. Changes in the width of the nano rough regions also resulted in changes in osteoblast morphology, thus, suggesting there is an optimal pattern dimension that osteoblasts prefer. In summary, results of this study provided evidence that aligned nanophase metal features on the surface of titanium improved early osteoblast functions (morphology and adhesion) promising for their long term functions, criteria necessary to improve orthopedic implant efficacy.


Assuntos
Materiais Biocompatíveis/química , Nanopartículas/química , Nanopartículas/ultraestrutura , Osteoblastos/citologia , Osteoblastos/fisiologia , Titânio/química , Adesão Celular , Linhagem Celular , Tamanho Celular , Humanos , Teste de Materiais , Propriedades de Superfície
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