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1.
J Biomed Mater Res A ; 104(2): 406-12, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26418753

RESUMO

The cardiovasculature is an emerging niche for polyimide microdevices, yet the biocompatibility of polyimides with human endothelial cells has not been reported in the literature. In this study, we have evaluated an experimental polyimide-based pressure sensor for biological safety to determine its suitability for intravascular operation by using an in vitro model of human endothelium, following ISO 10993-5 protocols for extract tests and direct contact tests. First, SV-HCEC cells were incubated with extracts derived from common microfabrication polyimides utilized in the transducer (PMDA-ODA, BPDA-PPD, and a proprietary thermoplastic adhesive), and then labeled with selective probes to evaluate the effect of the polyimides on mitochondria and cell viability. Flow cytometry analysis showed that incubation of SV-HCECs with polyimide extracts resulted in no significant change in mitochondrial membrane potential (detected by JC-1) or apoptotic (annexin V) and necrotic (propidium iodide) cell death, when compared to incubation with extracts of high-density polyethylene (HDPE) and untreated cells used as negative controls. Second, primary human endothelial cells were incubated in direct contact with the completed sensor and then labeled with selective probes for live-dead analysis (calcein-AM, ethidium homodimer-1). Endothelial cells showed no loss of viability when compared to negative controls. Combined, the studies show no significant change in early markers of stress or more strict markers of viability in endothelial cells treated with the polyimides tested. We conclude that these common microfabrication polyimides and the derived sensor are not cytotoxic to human endothelial cells, the primary cell type that cardiovascular sensors will contact in vivo.


Assuntos
Apoptose/efeitos dos fármacos , Células Endoteliais/metabolismo , Teste de Materiais/métodos , Membranas Mitocondriais/efeitos dos fármacos , Resinas Sintéticas/química , Células Endoteliais/patologia , Humanos , Polietileno/química
2.
Biotechnol Bioeng ; 111(2): 418-24, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24114441

RESUMO

The rise in the use of biomedical devices and implants has seen a concomitant surge in the advent of device-related nosocomial (hospital-acquired) infections of bacterial and fungal origins. The most common nosocomial fungal infection is candidiasis caused mainly by Candida albicans biofilms. Candidiasis is associated with an unacceptably high mortality rate, and there is an urgent need for the discovery of new antifungal drugs that prevent or control biofilm formation. To this end, we recently developed an ultra-high-throughput microarray platform consisting of nano-scale biofilms of C. albicans encapsulated in collagen or alginate hydrogel matrices for antifungal drug screening. Here, we report that the choice of matrix influences the apparent susceptibility of C. albicans to the common antifungal drugs, amphotericin B, and caspofungin. While amphotericin B is equally effective against biofilms grown in collagen and alginate matrices, caspofungin is effective only against biofilms grown only in alginate, but not in collagen. We demonstrate differences in the distribution of the drugs in the two matrices may contribute to the susceptibility of C. albicans nano-biofilms. In a larger context, our results highlight the importance of the choice of matrix as a parameter in 3D cell encapsulation, and suggest a screening strategy to predict drug performance in vivo.


Assuntos
Antifúngicos/farmacologia , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Testes de Sensibilidade Microbiana/métodos , Anfotericina B/farmacologia , Caspofungina , Células Imobilizadas/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos/métodos , Equinocandinas/farmacologia , Hidrogel de Polietilenoglicol-Dimetacrilato , Lipopeptídeos
3.
J Tissue Eng Regen Med ; 6(3): 193-204, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21400666

RESUMO

This study sought to establish a chronic total occlusion (CTO) model with cell-mediated calcium deposits in rabbit femoral arteries. CTO is the most severe case in atherosclerosis and contains calcium deposits. Previous animal models of CTO do not mimic the gradual occlusion of arteries or have calcium in physiological form. In the present study we tested the strategy of placing tissue-engineering scaffolds preloaded with cells in arteries to develop a novel CTO model. Primary human osteoblasts (HOBs) were first cultured in vitro on polycaprolactone (PCL) scaffolds with 5 ng TGFß1 loading for 28 days for precalcification. The HOB-PCL construct was then implanted into a rabbit femoral artery for an additional 3, 10 or 28 days. At the time of sacrifice, angiograms and gross histology of arteries were captured to examine the occlusion of arteries. Fluorescent staining of calcium and EDS detection of calcium were used to evaluate the presence and distribution of calcium inside arteries. Rabbit femoral arteries were totally occluded over 28 days. Calcium was presented at CTO sites at 3, 10 and 28 days, with the day 10 specimens showing the maximum calcium. Chronic inflammatory response and recanalization were observed in day 28 CTO sites. A novel CTO model with cell-mediated calcium has been successfully established in a rabbit femoral artery. This model can be used to develop new devices and therapies to treat severe atherosclerotic occlusion.


Assuntos
Arteriopatias Oclusivas/patologia , Aterosclerose/patologia , Cálcio/metabolismo , Artéria Femoral/patologia , Osteoblastos/metabolismo , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Animais , Arteriopatias Oclusivas/complicações , Aterosclerose/complicações , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Modelos Animais de Doenças , Artéria Femoral/diagnóstico por imagem , Artéria Femoral/efeitos dos fármacos , Fluorescência , Humanos , Neovascularização Fisiológica/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Poliésteres , Coelhos , Radiografia , Espectrometria por Raios X , Coloração e Rotulagem , Fator de Crescimento Transformador beta1/farmacologia
4.
J Tissue Eng Regen Med ; 6(9): 687-95, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21932279

RESUMO

Total atherosclerotic occlusion is a leading cause of death. Recent animal models of this disease are devoid of cell-mediated calcification and arteries are often not occluded gradually. This study is part of a project with the objective of developing a new model featuring the above two characteristics, using a tissue-engineering scaffold. The amount and distribution of calcium deposits in primary human osteoblast (HOB) cultures on polycaprolactone (PCL) scaffolds under flow conditions were investigated. HOBs were cultured on PCL scaffolds with TGF-ß1 loadings of 0 (control), 5 and 50 ng. HOB-PCL constructs were cultured in spinner flasks. Under flow conditions, cell numbers present in HOB cultures on PCL scaffolds increased from day 7 to day 14, and most calcification was induced at day 21. TGF-ß1 loadings of 5 and 50 ng did not show a significant difference in ALP activity, cell numbers and amount of calcium deposited in HOB cultures, but calcium staining showed that 50 ng TGF-ß1 had higher calcium deposited on both days 21 and 28 under flow conditions compared with 5 ng of loading. Amount of calcium deposited by HOBs on day 28 showed a decrease from their levels on day 21. PCL degradation may be a factor contributing to this loss. The results indicate that cell-induced calcification can be achieved on PCL scaffolds under flow conditions. In conclusion, TGFß1-HOB loaded PCL can be applied to create a model for total atherosclerotic occlusion with cell-deposited calcium in animal arteries.


Assuntos
Calcinose , Osteoblastos/metabolismo , Osteoblastos/patologia , Poliésteres/química , Alicerces Teciduais/química , Fosfatase Alcalina/metabolismo , Animais , Aterosclerose/etiologia , Aterosclerose/metabolismo , Aterosclerose/patologia , Reatores Biológicos , Cálcio/metabolismo , Contagem de Células , Diferenciação Celular , Células Cultivadas , Materiais Revestidos Biocompatíveis/química , Humanos , Teste de Materiais , Modelos Cardiovasculares , Osteoblastos/efeitos dos fármacos , Reologia , Engenharia Tecidual/métodos , Fator de Crescimento Transformador beta1/administração & dosagem , Fator de Crescimento Transformador beta1/química
5.
Ann Biomed Eng ; 39(10): 2501-9, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21769541

RESUMO

Regeneration of bone in large segmental bone defects requires regeneration of both cortical bone and trabecular bone. A scaffold design consisting of a hydroxyapatite (HA) ring surrounding a polylactic acid (PLA) core simulates the structure of bone and provides an environment for indirect and direct co-culture conditions. In this experiment, human umbilical vein endothelial cells (EC) and normal human primary osteoblasts (OB) were co-cultured to evaluate cell migration and interactions within this biphasic composite scaffold. Both cell types were able to migrate between the different material phases of the scaffold. It was also observed that OB migration increased when they were co-cultured with ECs, whereas EC migration decreased in co-culture. The results show that co-culture of ECs and OBs in this composite biphasic scaffold allows for migration of cells throughout the scaffold and that pre-seeding a scaffold with ECs can increase OB infiltration into desired areas of the scaffold.


Assuntos
Transplante Ósseo/métodos , Movimento Celular , Células Endoteliais da Veia Umbilical Humana , Osteoblastos , Engenharia Tecidual/métodos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/metabolismo , Regeneração Óssea , Osso e Ossos , Diferenciação Celular , Células Cultivadas , Técnicas de Cocultura/métodos , Durapatita/química , Durapatita/metabolismo , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Ácido Láctico/química , Ácido Láctico/metabolismo , Osteoblastos/citologia , Osteoblastos/metabolismo , Poliésteres , Polímeros/química , Polímeros/metabolismo , Porosidade
6.
J Biomed Mater Res B Appl Biomater ; 98(2): 280-9, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21604365

RESUMO

Commercially available drug-eluting stents have the potential to induce inflammatory and hypersensitive adverse reactions due to their polymer coating. The use of self assembled monolayers (SAMs) as an alternate drug delivery platform for stents has recently been demonstrated. In this study, the formation and stability of phosphonic acid SAMs were investigated using the material and surface preparation commonly used to make ultra-thin stent struts-electropolished L605 Cobalt Chromium (CoCr) alloy. Methyl (⁻CH3) and carboxylic acid (⁻OOH) terminated phosphonic acid SAMs were coated on electropolished CoCr alloy using a combination of solution immersion and dip-evaporation cycle deposition methods. SAMs-coated CoCr alloy specimens were thoroughly characterized using contact angle goniometry, Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM). These characterizations suggested that uniform and well-ordered monolayers were coated on the electropolished CoCr alloy. The long-term physiological stability of monolayers was investigated in tris-buffered saline (TBS) at 37°C for up to 28 days. Contact angles, FTIR, XPS, and AFM suggested that both ⁻CH3 and ⁻COOH terminated phosphonic acid SAMs desorb from electropolished CoCr alloy surfaces in a biphasic manner. A significant desorption of ⁻CH3 and ⁻COOH terminated SAMs occurs within 1-3 days followed by a slower desorption for up to 28 days. Thus, there is a need to develop techniques that can improve the long-term stability of SAMs on electropolished CoCr alloy for stent and other biomedical applications.


Assuntos
Ligas de Cromo/uso terapêutico , Materiais Revestidos Biocompatíveis/síntese química , Stents Farmacológicos , Ligas de Cromo/química , Materiais Revestidos Biocompatíveis/química , Cobalto , Sistemas de Liberação de Medicamentos , Propriedades de Superfície
7.
Spine (Phila Pa 1976) ; 36(26): E1675-85, 2011 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-21494194

RESUMO

STUDY DESIGN: In vitro biotribological wear particulate investigation. OBJECTIVE: To characterize poly-ether-ether-ketone (PEEK)-OPTIMA wear particulate generated from a series of wear tests used to evaluate the wear resistance and long-term biodurability of NUBAC, a PEEK-on-PEEK articulating nucleus replacement device, and compare with wear particulate associated with hip and knee total joint arthroplasties. SUMMARY OF BACKGROUND DATA: The use of PEEK in spinal arthroplasty represents a unique application of this material. Clinically, osteolysis, osteolytic changes, and adverse reactions to metal ions have been documented in spinal arthroplasty. Therefore, it is critically important to analyze the PEEK wear particulate to evaluate its resultant biologic reactivity. Historically, scanning electron microscopy (SEM) has been used for wear debris characterization. Light scattering, specifically laser diffraction, has also been successfully used. The combined use of both techniques may provide a more comprehensive analysis than either method alone. METHODS: Proteinacious serum containing PEEK wear debris generated from four groups of devices from separate wear tests underwent enzymatic and acid digestion. The particulate was analyzed using laser diffraction in duplicate, followed by SEM analysis. RESULTS: Laser diffraction analysis demonstrated a relatively large mean particle diameter on the basis of particle volume (16.5-40.0 µm) as compared with particle number (0.9-2.2 µm). For all groups, more than 50% of debris was larger than 5.0 µm. SEM analysis revealed a mean particle size consistent with the number-based laser diffraction results. The morphology of the wear particulate appeared to be similar for all the groups analyzed. CONCLUSION: The analysis of the particles generated from an articulating PEEK-on-PEEK nucleus replacement device shows debris within size ranges typical of other total joint arthroplasty implants, with relatively round morphology, along with the results suggesting a reduced particle load. These attributes tend to diminish the potential of these PEEK particles to elicit an inflammatory response.


Assuntos
Artroplastia de Substituição/métodos , Análise de Falha de Equipamento/métodos , Disco Intervertebral/cirurgia , Próteses e Implantes , Benzofenonas , Materiais Biocompatíveis/uso terapêutico , Fenômenos Biomecânicos , Humanos , Disco Intervertebral/fisiopatologia , Deslocamento do Disco Intervertebral/fisiopatologia , Deslocamento do Disco Intervertebral/cirurgia , Prótese Articular , Cetonas/uso terapêutico , Lasers , Vértebras Lombares/cirurgia , Teste de Materiais , Microscopia Eletrônica de Varredura , Avaliação de Resultados em Cuidados de Saúde , Tamanho da Partícula , Polietilenoglicóis/uso terapêutico , Polímeros , Amplitude de Movimento Articular
8.
Acta Biomater ; 6(8): 3242-55, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20188873

RESUMO

Open fractures are common in battlefields, motor vehicle accidents, gunshot wounds, sports injuries, and high-energy falls. Such fractures are treated using hydroxyapatite (HA)-based bone graft substitutes. However, open fracture wounds are highly susceptible to bacterial infections. Hence, this study was focused on incorporating antibacterial properties to HA using silver (Ag) carrying self-assembled monolayers (SAMs). Also, the stability of Ag carrying SAMs on HA was investigated under sterilization and physiological conditions. Initially, the -COOH terminated phosphonic acid SAMs of two different chain lengths (11 carbon atoms - shorter chain and 16 carbon atoms - longer chain) were deposited on HA. Antibacterial SAMs (ASAMs) were prepared by chemically attaching Ag to shorter and longer chain SAMs coated HA. X-ray photoelectron spectroscopy, atomic force microscopy, and contact angle goniometry collectively confirmed the attachment of Ag onto SAMs coated HA. The bacterial adhesion study showed that the adherence of Staphylococcus aureus was significantly reduced on ASAMs coated HA when compared to control-HA. The stability studies showed that gas plasma, dry heat and autoclave degraded most of the ASAMs on HA. UV irradiation did not damage the shorter chain ASAMs as vigorously as other treatments, while it degraded the longer chain ASAMs completely. Ethylene oxide treatment did not degrade the longer chain ASAMs unlike all other treatments but it severely damaged the shorter chain ASAMs. Both shorter and longer chain ASAMs significantly desorbed from the HA surfaces under physiological conditions although longer chain ASAMs exhibited better stability than shorter chain ASAMs. This study demonstrated the potential for using ASAMs to provide antibacterial properties to HA and the need for developing techniques to improve stability of SAMs under sterilization and physiological conditions.


Assuntos
Antibacterianos/farmacologia , Durapatita/química , Membranas Artificiais , Aderência Bacteriana/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Microscopia de Força Atômica , Microscopia Eletrônica de Varredura , Espectroscopia Fotoeletrônica , Prata/farmacologia , Staphylococcus aureus/citologia , Staphylococcus aureus/efeitos dos fármacos , Esterilização , Propriedades de Superfície/efeitos dos fármacos
9.
J Biomed Mater Res B Appl Biomater ; 90(2): 789-801, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19274726

RESUMO

Drug-eluting stents (DES) are implanted in patients to treat in-stent restenosis. Commercially available DES use polymers for coating and releasing drugs. Several studies have showed that polymer coatings cause adverse reactions. Delayed endothelialization of polymer-coated DES leads to late stent thrombosis. Recently, the potential for using self-assembled monolayers (self-assembled monolayers (SAMs)-organic constructs composed of (a) chemical groups which attach to metal surfaces, (b) long hydrocarbon chains, and (c) terminal functional groups) as an alternate drug delivery system for coronary stents has been demonstrated. In this study, the interaction of human aortic endothelial cells (HAECs) with SAMs and therapeutic SAMs (therapeutic self-assembled monolayers (TSAMs)-SAMs derivatized with the drug, flufenamic acid) was investigated. HAECs were cultured on plain glass, control, SAMs-, and TSAMs-coated titanium (Ti) and gold (Au) specimens. The viability and proliferation of HAECs were investigated using MTT colorimetric assay. The adhesion of HAECs on SAMs and TSAMs was equivalent to that of control metal surfaces and superior to that of plain glass surfaces. The cells continued to proliferate on both SAMs and TSAMs even though the rate of proliferation was slower than plain glass or control-Ti. The spreading of HAECs on TSAMs with typical polygonal shape indicated that these surfaces are conducive to endothelialization. The expression of surface adhesion protein, platelet endothelial cell adhesion molecule-1, on TSAMs indicated that the endothelial cells preserved their phenotype on these surfaces. Thus, this study demonstrated that SAMs and TSAMs do not elicit an adverse response from endothelial cells in in vitro conditions.


Assuntos
Materiais Biocompatíveis/química , Materiais Revestidos Biocompatíveis/química , Stents Farmacológicos , Células Endoteliais/patologia , Aorta/patologia , Adesão Celular , Proliferação de Células , Sobrevivência Celular , Sistemas de Liberação de Medicamentos , Células Endoteliais/efeitos dos fármacos , Endotélio Vascular/patologia , Ouro/química , Teste de Materiais , Metais/química , Polímeros/química , Titânio/química
10.
Biomaterials ; 29(34): 4561-73, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18790530

RESUMO

Currently available drug-eluting stents (DES) use polymers for coating and releasing drugs. Increasing evidence suggests that inflammatory and hypersensitive reactions are caused by such polymer coatings. This study focused on developing new techniques for delivering drugs directly from metal implant surfaces. Hydroxyl-terminated self-assembled monolayers (SAMs) were coated on Au and Ti surfaces. Therapeutic self-assembled monolayers (TSAMs) were prepared by chemically attaching the model drug, flufenamic acid, to SAM coated metal surfaces. Three different methods of esterification (acid chloride esterification, dry heat esterification, and direct esterification) were explored to attach flufenamic acid to SAMs. TSAMs were characterized using X-ray photoelectron spectroscopy, fluorescence microscopy, atomic force microscopy, and contact angle goniometry. These techniques collectively confirmed the attachment of drug onto SAM coated metal surfaces. In vitro drug release was investigated by immersing TSAM coated metal specimens in tris-buffered saline (TBS) at 37 degrees C for 28 days. TBS was analyzed at 1, 3, 7, 14, 21, and 28 days for the amount of drug eluted using high performance liquid chromatography. Large data scatter was observed for the release profiles of TSAMs prepared by acid chloride esterification. TSAMs prepared by dry heat and direct esterification methods showed an initial burst release of the drug followed by a sustained slow release for up to 2 weeks. Thus, this study suggests the potential for using self-assembled monolayers as an alternate system for delivering drugs from coronary stents and other metal implants.


Assuntos
Materiais Revestidos Biocompatíveis/química , Sistemas de Liberação de Medicamentos/métodos , Ouro/química , Titânio/química , Cromatografia Líquida de Alta Pressão , Sistemas de Liberação de Medicamentos/instrumentação , Esterificação , Ácido Flufenâmico/química , Microscopia de Força Atômica , Microscopia de Fluorescência , Análise Espectral , Propriedades de Superfície , Fatores de Tempo
11.
Langmuir ; 24(13): 6774-84, 2008 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-18512878

RESUMO

Methyl- and hydroxyl-terminated phosphonic acid self-assembled monolayers (SAMs) were coated on Ti from aqueous solution. Dodecyl phosphate and dodecyltrichlorosilane SAMs were also coated on Ti using solution-phase deposition. The stability of SAMs on Ti was investigated in Tris-buffered saline (TBS) at 37 degrees C using X-ray photoelectron spectroscopy, contact angle goniometry, and atomic force microscopy. For comparison purposes, a hydroxyl-terminated thiol SAM was coated on Au, and its stability was also investigated under similar conditions. In TBS, a significant proportion of phosphonic acid or phosphate molecules were desorbed from the Ti surface within 1 day, while the trichlorosilane SAM on Ti or thiol SAM on Au was stable for up to 7 days under similar conditions. The stability of hydroxyl-terminated phosphonic acid SAM coated Ti and thiol SAM coated Au was investigated in ambient air and ultraviolet (UV) light. In ambient air, the phosphonic acid SAM on Ti was stable for up to 14 days, while the thiol SAM on Au was not stable for 1 day. Under UV-radiation exposure, the alkyl chains of the phosphonic acid SAM were decomposed, leaving only the phosphonate groups on the Ti surface after 12 h. Under similar conditions, decomposition of alkyl chains of the thiol SAM was observed on the Au surface accompanied by oxidation of thiolates.


Assuntos
Ouro/química , Titânio/química , Soluções Tampão , Microscopia de Força Atômica , Análise Espectral , Água/química
12.
Curr Top Med Chem ; 8(4): 281-9, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18393891

RESUMO

Delivery of therapeutic agents from self-assembled monolayers (SAMs) on 316L stainless steel (SS) has been demonstrated as a viable method to deliver drugs for localized coronary artery stent application. SAMs are highly-ordered, nano-sized molecular coatings, adding 1-10 nm thickness to a surface. Hydroxyl terminated alkanethiol SAMs of 11-mercapto-1-undecanol (-OH SAM) were formed on 316L SS with 48 hr immersion in ethanolic solutions. Attachment of ibuprofen (a model drug) to the functional SAMs was carried out in toluene for 5 hrs at 60 degrees C using Novozume-435 as a biocatalyst. SAM formation and subsequent attachment of ibuprofen was characterized collectively using X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), and contact angle (CA) measure-ments. The quantitative in vitro release of ibuprofen into a "physiological" buffer solution was characterized using reverse phase HPLC. Drug release kinetics showed that 14.1 microg of ibuprofen eluted over a period of 35 days with 2.7microg being eluted in the first day and the remaining being eluted over a period of 35 days. The drug release kinetics showed an increase in ibuprofen elution that occurred during first 14 days (2.7microg in 1 day to 9.5 microg in 14 days), following which there was a decrease in the rate of elution. Thus, functional SAMs on 316L SS could be used as tethers for drug attachment and could serve as a drug delivery mechanism from stainless steel implants such as coronary artery stents.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Stents Farmacológicos , Nanoestruturas/química , Preparações Farmacêuticas/administração & dosagem , Aço Inoxidável/química , Cromatografia Líquida de Alta Pressão , Stents Farmacológicos/normas , Ibuprofeno/administração & dosagem , Ibuprofeno/química , Preparações Farmacêuticas/química , Espectroscopia de Infravermelho com Transformada de Fourier
13.
J Tissue Eng Regen Med ; 1(3): 211-7, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-18038413

RESUMO

PURPOSE: Adipose-derived stromal cells (ADSCs) have been shown to increase angiogenesis in ischemic tissue. Maintaining cell survival and facilitating angiogenesis in ischemic tissue, however, continues to be the major challenge of ADSCs implantation. Recently, bioengineered scaffolds were introduced to support and facilitate cell culture and differentiation. The effects of a surface modified three-dimensional (3D) scaffold on ADSC function have not been investigated. Accordingly, the objective of this study was to determine the influence of a gas-plasma treated scaffold on ADSC growth, differentiation into endothelial cell, and angiogenic gene expression. METHODS: Freshly isolated mouse ADSCs were characterized by flow cytometry and cultured into wells containing gas-plasma treated scaffolds, non-treated scaffolds, or control wells. Either endothelial growth media or differentiation media was used to alter cell environment. After 3 and 6 days, cell proliferation was analyzed. VEGF concentration in the medium was measured by ELISA. Gene expression was quantified by real-time PCR for VEGF receptor-2 (KDR), cyclooxygenase-2 (COX-2) and matrix metalloproteinases-2 (MMP-2). RESULTS: ADSCs expressed stem/endothelial progenitor markers CD34 and CD133 and endothelial cell marker CD31. ADSCs grew in the 3D scaffold. Cells grown on gas-plasma treated scaffolds displayed significantly increased expression of VEGF, COX-2, and MMP-2 when grown in differentiation but not growth media. When cultured in endothelial growth media, VEGF secretion and the expression of KDR, COX-2 and MMP-2 were lower in 3D scaffolds than controls. CONCLUSIONS: This study suggests that 3D scaffolds, especially gas-plasma treated scaffolds, support ADSC growth and support differentiation into endothelial cells.


Assuntos
Tecido Adiposo/citologia , Diferenciação Celular , Células Estromais/citologia , Alicerces Teciduais , Tecido Adiposo/irrigação sanguínea , Tecido Adiposo/metabolismo , Animais , Biomarcadores/metabolismo , Proliferação de Células , Células Cultivadas , Colágeno/metabolismo , Meios de Cultivo Condicionados , Combinação de Medicamentos , Gases , Regulação da Expressão Gênica , Laminina/metabolismo , Camundongos , Neovascularização Fisiológica , Proteoglicanas/metabolismo , Células-Tronco/citologia , Células-Tronco/metabolismo , Células Estromais/metabolismo , Propriedades de Superfície , Fator A de Crescimento do Endotélio Vascular/metabolismo
14.
Diabetes Care ; 30(1): 14-20, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17192326

RESUMO

OBJECTIVE: The purpose of this study was to evaluate the effectiveness of a temperature monitoring instrument to reduce the incidence of foot ulcers in individuals with diabetes who have a high risk for lower extremity complications. RESEARCH DESIGN AND METHODS: In this physician-blinded, randomized, 15-month, multicenter trial, 173 subjects with a previous history of diabetic foot ulceration were assigned to standard therapy, structured foot examination, or enhanced therapy groups. Each group received therapeutic footwear, diabetic foot education, and regular foot care. Subjects in the structured foot examination group performed a structured foot inspection daily and recorded their findings in a logbook. If standard therapy or structured foot examinations identified any foot abnormalities, subjects were instructed to contact the study nurse immediately. Subjects in the enhanced therapy group used an infrared skin thermometer to measure temperatures on six foot sites each day. Temperature differences >4 degrees F (>2.2 degrees C) between left and right corresponding sites triggered patients to contact the study nurse and reduce activity until temperatures normalized. RESULTS: The enhanced therapy group had fewer foot ulcers than the standard therapy and structured foot examination groups (enhanced therapy 8.5 vs. standard therapy 29.3%, P = 0.0046 and enhanced therapy vs. structured foot examination 30.4%, P = 0.0029). Patients in the standard therapy and structured foot examination groups were 4.37 and 4.71 times more likely to develop ulcers than patients in the enhanced therapy group. CONCLUSIONS: Infrared temperature home monitoring, in serving as an "early warning sign," appears to be a simple and useful adjunct in the prevention of diabetic foot ulcerations.


Assuntos
Diabetes Mellitus Tipo 2/reabilitação , Pé Diabético/prevenção & controle , Úlcera do Pé/prevenção & controle , Educação de Pacientes como Assunto , Temperatura Cutânea , Adulto , Idoso , Idoso de 80 Anos ou mais , Pé Diabético/epidemiologia , Feminino , Úlcera do Pé/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Seleção de Pacientes , Exame Físico , Projetos de Pesquisa , Medição de Risco , Autocuidado , Sapatos , Ensino/métodos , Fatores de Tempo , Gravação de Videoteipe
15.
Biomaterials ; 28(9): 1689-710, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17188349

RESUMO

The objective of this review is to describe the suitability of different biomaterials as coronary stents. This review focuses on the following topics: (1) different materials used for stents, (2) surface characteristics that influence stent-biology interactions, (3) the use of polymers in stents, and (4) drug-eluting stents, especially those that are commercially available.


Assuntos
Ligas/química , Anticoagulantes/administração & dosagem , Prótese Vascular , Materiais Revestidos Biocompatíveis/química , Vasos Coronários/cirurgia , Implantes de Medicamento/administração & dosagem , Stents , Animais , Anticoagulantes/química , Materiais Revestidos Biocompatíveis/farmacologia , Vasos Coronários/efeitos dos fármacos , Implantes de Medicamento/química , Humanos , Desenho de Prótese
16.
J Am Podiatr Med Assoc ; 96(2): 91-5, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16546944

RESUMO

This investigation evaluates the effects of diabetes on the mechanical properties of human bone, specifically, the tibia. Seven diabetic and seven nondiabetic human (male) cadaveric distal tibiae were used in this study. The average age of the diabetic cadaveric samples was 51 years (range, 46-61 years), and the average age of the nondiabetic cadaveric samples was 75 years (range, 67-85 years). Three-point bending tests for strength and stiffness were performed on a small sample of each distal tibia. Each specimen was loaded at a constant rate until failure. From the recorded curve of load versus displacement, the ultimate and yield strength of bone and the bending modulus of bone were calculated. The diabetic samples were generally weaker than the older, nondiabetic samples, but no statistically significant differences were found in the elastic modulus (P = .29), yield strength (P = .90), ultimate strength (P = .46), and fracture toughness (P = .78), leading to speculation that diabetes has an effect similar to that of aging on the musculoskeletal system.


Assuntos
Diabetes Mellitus/fisiopatologia , Tíbia/fisiopatologia , Idoso , Cadáver , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Mecânico , Suporte de Carga/fisiologia
17.
Catheter Cardiovasc Interv ; 67(3): 412-6, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16475164

RESUMO

We have hypothesized that oxygen enhanced three-dimensional microporous poly-L-lactic acid (L-PLA) bioabsorbable polymer constructs could be implanted to produce a subacute occlusion in a porcine coronary artery, forming a thrombofibrotic occlusion containing microvascular channels. Chronic total occlusion (CTO) is increasingly prevalent in patients who present for percutaneous interventions. No reproducible animal coronary model simulating human CTOs has previously been developed. Swine coronary arteries were cannulated and a microporous L-PLA polymer pledget was advanced into a preselected segment of coronary. The coronary arteries were angiographically re-imaged at day 3, day 10, and day 28, to document the presence or absence of an occlusion. Histopathology was also performed at each time point to evaluate the lesion characteristics. A novel three-dimensional L-PLA microporous polymer construct, when implanted into porcine coronary arteries, reproducibly results in the development of a CTO at day 3. The histopathology in this porcine coronary model of CTO at day 28 closely mimics human coronary CTO, including the presence of microvascular channels and dense collagen and elastic tissue in the occlusion.


Assuntos
Materiais Biocompatíveis/química , Doença das Coronárias/patologia , Modelos Animais de Doenças , Poliésteres/química , Implantes Absorvíveis , Animais , Doença Crônica , Oxigênio , Porosidade , Reprodutibilidade dos Testes , Suínos
18.
Langmuir ; 22(3): 901-5, 2006 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-16430246

RESUMO

Lipase catalyzed esterification of therapeutic drugs to functional self-assembled monolayers (SAMs) on 316L stainless steel (SS) after assembly has been demonstrated. SAMs of 16-mercaptohexadecanoic acid (-COOH SAM) and 11-mercapto-1-undecanol (-OH SAM) were formed on 316L SS, and lipase catalysis was used to attach therapeutic drugs, perphenazine and ibuprofen, respectively, on these SAMs. The reaction was carried out in toluene at 60 degrees C for 5 h using Novozyme-435 as the biocatalyst. The FTIR spectra after surface modification of -OH SAMs showed the presence of the C=O stretching bands at 1745 cm(-1), which was absent in the FTIR spectra of -OH SAMs. Similarly, the FTIR spectra after the reaction of the -COOH SAM with perphenazine showed two peaks in the carbonyl region, a peak at 1764 cm(-1), which is the representative peak for the C=O stretching for esters. The second peak at 1681 cm(-1) is assigned to the C=O stretching of the remaining unreacted terminal COOH. XPS spectra after lipase catalysis with ibuprofen showed a photoelectron peak evolving at 288.5 eV which arises from the carbon (C=O) of the carboxylic acid of the drug (ibuprofen). Similarly for -COOH SAMs, after esterifiation we see a small, photoelectron peak evolving at 286.5 eV which corresponds to the C in the methylene groups adjacent to the oxygen (C-O), which should evolve only after the esterification of perphenazine with the -COOH SAM. Thus, lipase catalysis provides an alternate synthetic methodology for surface modification of functional SAMs after assembly.


Assuntos
Lipase/metabolismo , Aço Inoxidável , Propriedades de Superfície , Catálise , Espectroscopia de Infravermelho com Transformada de Fourier
19.
Biomaterials ; 27(5): 752-7, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16112725

RESUMO

A total of 750 images of individual ultra-high molecular weight polyethylene (UHMWPE) particles isolated from periprosthetic failed hip, knee, and shoulder arthroplasties were extracted from archival scanning electron micrographs. Particle size and morphology was subsequently analyzed using computerized image analysis software utilizing five descriptors found in ASTM F1877-98, a standard for quantitative description of wear debris. An online survey application was developed to display particle images, and allowed ten respondents to classify particle morphologies according to commonly used terminology as fibers, flakes, or granules. Particles were categorized based on a simple majority of responses. All descriptors were evaluated using a one-way ANOVA and Tukey-Kramer test for all-pairs comparison among each class of particles. A logistic regression model using half of the particles included in the survey was then used to develop a mathematical scheme to predict whether a given particle should be classified as a fiber, flake, or granule based on its quantitative measurements. The validity of the model was then assessed using the other half of the survey particles and compared with human responses. Comparison of the quantitative measurements of isolated particles showed that the morphologies of each particle type classified by respondents were statistically different from one another (p<0.05). The average agreement between mathematical prediction and human respondents was 83.5% (standard error 0.16%). These data suggest that computerized descriptors can be feasibly correlated with subjective terminology, thus providing a basis for a common vocabulary for particle description which can be translated into quantitative dimensions.


Assuntos
Prótese Articular , Polietilenos/química , Tamanho da Partícula , Polietilenos/classificação
20.
Biomed Mater ; 1(4): L11-5, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18458401

RESUMO

The loading of therapeutic amounts of drug on a nanoporous TiO(2) surface is described. This novel drug-loading scheme on a biocompatible surface, when employed on medical implants, will benefit patients who require the deployment of drug-eluting implants. Anticoagulants, analgesics and antibiotics can be considered on the associated implants for drug delivery during the time of maximal pain or risk for patients undergoing orthopedic procedures. Therefore, this scheme will maximize the chances of patient recovery.


Assuntos
Portadores de Fármacos/química , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Preparações Farmacêuticas/química , Veículos Farmacêuticos/química , Titânio/química , Absorção , Materiais Biocompatíveis/química , Composição de Medicamentos/métodos , Teste de Materiais , Tamanho da Partícula , Preparações Farmacêuticas/administração & dosagem , Porosidade
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