Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 8 de 8
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Int J Mol Sci ; 22(12)2021 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-34199303

RESUMO

The main purpose of new stent technologies is to overcome unfavorable material-related incompatibilities by producing bio- and hemo-compatible polymers with anti-inflammatory and anti-thrombogenic properties. In this context, wettability is an important surface property, which has a major impact on the biological response of blood cells. However, the influence of local hemodynamic changes also influences blood cell activation. Therefore, we investigated biodegradable polymers with different wettability to identify possible aspects for a better prediction of blood compatibility. We applied shear rates of 100 s-1 and 1500 s-1 and assessed platelet and monocyte activation as well as the formation of CD62P+ monocyte-bound platelets via flow cytometry. Aggregation of circulating platelets induced by collagen was assessed by light transmission aggregometry. Via live cell imaging, leukocytes were tracked on biomaterial surfaces to assess their average velocity. Monocyte adhesion on biomaterials was determined by fluorescence microscopy. In response to low shear rates of 100 s-1, activation of circulating platelets and monocytes as well as the formation of CD62P+ monocyte-bound platelets corresponded to the wettability of the underlying material with the most favorable conditions on more hydrophilic surfaces. Under high shear rates, however, blood compatibility cannot only be predicted by the concept of wettability. We assume that the mechanisms of blood cell-polymer interactions do not allow for a rule-of-thumb prediction of the blood compatibility of a material, which makes extensive in vitro testing mandatory.


Assuntos
Plaquetas/citologia , Comunicação Celular/efeitos dos fármacos , Monócitos/citologia , Monócitos/efeitos dos fármacos , Poliésteres/farmacologia , Plaquetas/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Humanos , Agregação Plaquetária/efeitos dos fármacos , Água , Molhabilidade
2.
Biomed Mater ; 16(1): 015022, 2020 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-33022660

RESUMO

An ongoing challenge in drug delivery systems for a variety of medical applications, including cardiovascular diseases, is the delivery of multiple drugs to address numerous phases of a treatment or healing process. Therefore, an extended dual drug delivery system (DDDS) based on our previously reported cardiac DDDS was generated. Here we use the polymer poly(L-lactide) (PLLA) as drug carrier with the cytostatic drug Paclitaxel (PTX) and the endothelial cell proliferation enhancing growth factor, human vascular endothelial growth factor (VEGF), to overcome typical in-stent restenosis complications. We succeeded in using one solution to generate two separate DDDS via spray coating (film) and electrospinning (nonwoven) with the same content of PTX and the same post processing for VEGF immobilisation. Both processes are suitable as coating techniques for implants. The contact angle analysis revealed differences between films and nonwovens. Whereas, the morphological analysis demonstrated nearly no changes occurred after immobilisation of both drugs. Glass transition temperatures (Tg ) and degree of crystallinity (χ) show only minor changes. The amount of immobilised VEGF on nonwovens was over 300% higher compared to the films. Also, the nonwovens revealed a much faster and over three times higher PTX release over 70 d compared to the films. The almost equal physical properties of nonwovens and films allow the comparison of both DDDS independently of their fabrication process. Both films and nonwovens have significantly increased in vitro cell viability for human umbilical vein endothelial cells (EA.hy926) with dual loaded PTX and VEGF compared to PTX-only loaded samples.

3.
Drug Deliv Transl Res ; 8(3): 719-728, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29532357

RESUMO

The successive incorporation of several drugs into the polymeric bulk of implants mostly results in loss of considerable quantity of one drug, and/or the loss in quality of the coating and also in changes of drug release time points. A dual drug delivery system (DDDS) based on poly-L-lactide (PLLA) copolymers combining the effective inhibition of smooth muscle cell proliferation while simultaneously promoting re-endothelialization was successfully developed. To overcome possible antagonistic drug interactions and the limitation of the polymeric bulk material as release system for dual drugs, a novel concept which combines the bulk and surface drug immobilization for a DDDS was investigated. The advantage of this DDDS is that the bulk incorporation of fluorescein diacetate (FDAc) (model drug for paclitaxel (PTX)) via spray coating enhanced the subsequent cleavable surface coupling of vascular endothelial growth factor (VEGF) via the crosslinker bissulfosuccinimidyl suberate (BS3). In the presence of the embedded FDAc, the VEGF loading and release are about twice times higher than in absence. Furthermore, the DDDS combines the diffusion drug delivery (FDAc or PTX) and the chemical controlled drug release, VEGF via hydrolysable ester bonds, without loss in quantity and quality of the drug release curves. Additionally, the performed in vitro biocompatibility study showed the bimodal influences of PTX and VEGF on human endothelial EA.hy926 cells. In conclusion, it was possible to show the feasibility to develop a novel DDDS which has a high potential for the medical application due to the possible easy and short modification of a polymer-based PTX delivery system.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Sistemas de Liberação de Medicamentos , Proteínas Imobilizadas/administração & dosagem , Paclitaxel/administração & dosagem , Polímeros/administração & dosagem , Fator A de Crescimento do Endotélio Vascular/administração & dosagem , Antineoplásicos Fitogênicos/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Células Endoteliais/efeitos dos fármacos , Fluoresceínas/administração & dosagem , Fluoresceínas/química , Humanos , Proteínas Imobilizadas/química , Paclitaxel/química , Polímeros/química , Propriedades de Superfície , Fator A de Crescimento do Endotélio Vascular/química
4.
Colloids Surf B Biointerfaces ; 159: 1-6, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-28778061

RESUMO

Knowledge about the interactions of biomaterials with biological matrices is still poor however crucial to future development in terms of how to cope with immunomodulatory adverse effects and to control the integration of implants into tissue or the targeting of nano devices. The appropriate design of a material depends on reliable data about the influence of oligomer or polymer configuration and dispersity as well as surface properties including chemical modifications. This work addressed the interaction of four polylactide (PLA) resomers, a well-established, biodegradable biomaterial, and two physiologically relevant proteins, which are ubiquitous in human serum - albumin (HSA) and fibrinogen (HFG). Bovine serum albumin (BSA) was carried along as reference. The amount and stability of protein binding to plane material was assessed by surface plasmon resonance (SPR), the formation of protein corona around NPs by nanoparticle tracking analysis (NTA). The results demonstrated the particular value of SPR and NTA as techniques for the characterisation and prediction of the interactions of implants or NPs with matrix components. Both techniques are complementary with respect to a deeper understanding of changes in the layer composition with time, which is known as the Vroman effect, and, therefore, are considered of value for affecting the interaction processes by material design.


Assuntos
Materiais Biocompatíveis/química , Fibrinogênio/química , Soroalbumina Bovina/química , Animais , Bovinos , Humanos , Ligação Proteica , Coroa de Proteína/química , Ressonância de Plasmônio de Superfície
5.
Acta Biomater ; 10(12): 5081-5089, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25204522

RESUMO

As it has been demonstrated that bioactive substances can be delivered locally using coated surgical suture materials, the authors developed a vascular endothelial growth factor (VEGF)-releasing suture material that should promote vascularization and potentially wound healing. In this context, the study focused on the characterization of the developed suture material and the verification of its biological activity, as well as establishing a coating process that allows reproducible and stable coating of a commercially available polydioxanone suture material with poly(l-lactide) (PLLA) and 0.1µg and 1.0µg VEGF. The in vitro VEGF release kinetics was studied using a Sandwich ELISA. The biological activity of the released VEGF was investigated in vitro using human umbilical vein endothelial cells. The potential of the VEGF-releasing suture material was also studied in vivo 5days after implantation in the hind limb of Wistar rats, when the histological findings were analyzed. The essential results, enhanced cell viability in vitro as well as significantly increased vascularization in vivo, were achieved using PLLA/1.0µg VEGF-coated suture material. Furthermore, ELISA measurements revealed a high reproducibility of the VEGF release behavior. Based on the results achieved regarding the dose-effect relationship of VEGF, the stability during its processing and the release behavior, it can be predicted that a bioactive suture material would be successful in later in vivo studies. Therefore, this knowledge could be the basis for future studies, where bioactive substances with different modes of action are combined for targeted, overall enhancement of wound healing.


Assuntos
Indutores da Angiogênese/administração & dosagem , Vasos Sanguíneos/crescimento & desenvolvimento , Implantes de Medicamento/administração & dosagem , Células Endoteliais/fisiologia , Neovascularização Fisiológica/fisiologia , Suturas , Fator A de Crescimento do Endotélio Vascular/administração & dosagem , Indutores da Angiogênese/química , Animais , Vasos Sanguíneos/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Difusão , Implantes de Medicamento/química , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Humanos , Técnicas In Vitro , Masculino , Ratos , Ratos Wistar , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/química
6.
J Mater Sci Mater Med ; 25(8): 2003-15, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24811954

RESUMO

The high degree of clinical routine in percutaneous transluminal coronary angioplasty (PTCA) with and without stenting has not changed the fact that a large number of coronary heart disease patients are still affected by post-operative complications such as restenosis and thrombosis. Because re-endothelialization is the crucial aspect of wound healing after cardiovascular implant surgery, there is a need for modern biomaterials to aid endothelial cells in their adhesion and functional recovery post-stenting. This study systematically examines the potential of numerous chemical polymer modifications with regard to endothelialization. Poly(ε-caprolactone) (PCL) and its chemically activated forms are investigated in detail, as well as the impact of polymer surface morphology and precoating with matrix protein. Human umbilical vein endothelial cells (HUVECs) are used to characterize endothelial cell responses in terms of in vitro viability and adhesion. As a potential component in drug eluting implants, VEGF is applied as stimulus to boost endothelial cell proliferation on the polymer. In conclusion, plasma chemical activation of PCL combined with VEGF stimulation best enhances in vitro endothelialization. Examining the impact of morphological, chemical and biological modifications of PCL, this study makes an important new contribution towards the existing body of work on polymer endothelialization.


Assuntos
Endotélio Vascular/efeitos dos fármacos , Poliésteres/química , Fator A de Crescimento do Endotélio Vascular/farmacologia , Materiais Biocompatíveis , Endotélio Vascular/citologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Microscopia Eletrônica , Propriedades de Superfície
7.
J Alzheimers Dis ; 38(3): 551-65, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24028865

RESUMO

Previous studies indicate an important role for the cellular prion protein (PrP(C)) in the development of Alzheimer's disease (AD) pathology. In the present study, we analyzed the involvement of PrP(C) in different pathological mechanisms underlying AD: the processing of the amyloid-ß protein precursor (AßPP) and its interaction with AßPP, tau, and different phosphorylated forms of the tau protein (p-tau). The effect of PrP(C) on tau expression was investigated in various cellular compartments using a HEK293 cell model expressing a tau mutant (3PO-tau) or wild type (WT)-tau. We could show that PrP(C) reduces AßPP cleavage, leading to decreased levels of Aß40 and sAßPP without changing the protein expression of AßPP, ß-secretase, or γ-secretase. Tau and its phosphorylated forms were identified as interactions partners for PrP(C), raising the question as to whether PrP(C) might also be involved in tau pathology. Overexpression of PrP(C) in PRNP and 3PO-tau transfected cells resulted in a reduction of 3PO-tau and p-tau as well as a decrease of 3PO-tau-related toxicity. In addition, we used the transgenic PrP(C) knockout (Prnp0/0) mouse line to study the dynamics of tau phosphorylation, an important pathological hallmark in the pathogenesis of AD in vivo. There, an effect of PrP(C) on tau expression could be observed under oxidative stress conditions but not during aging. In summary, we provide further evidence for interactions of PrP(C) with proteins that are known to be the key players in AD pathogenesis. We identified tau and its phosphorylated forms as potential PrP-interactors and report a novel protective function of PrP(C) in AD-like tau pathology.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Regulação da Expressão Gênica/genética , Mutação/genética , Príons/metabolismo , Proteínas tau/genética , Proteínas tau/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Encéfalo/irrigação sanguínea , Encéfalo/metabolismo , Linhagem Celular , Modelos Animais de Doenças , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neuroblastoma/patologia
8.
J Biomed Mater Res B Appl Biomater ; 98(1): 89-100, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21563304

RESUMO

Within this study, chemically modified polymer surfaces were to be developed, which should enhance the subsequent immobilization of various bioactive substances. To improve the hemocompatibility and endothelialization of poly(ε-caprolactone) (PCL) intended as scaffold material for bioartificial vessel prostheses, terminal amino groups via ammonia (NH3) plasma, oxygen (O2) plasma/aminopropyltriethoxysilane (APTES), and 4,4'-methylenebis(phenyl isocyanate) (MDI)/water were provided. Then, immobilization of the anti-inflammatory and antithrombogenic model drug acetylsalicylic acid (ASA) and vascular endothelial growth factor (VEGF) were performed by employing N,N-disuccinimidyl carbonate (DSC) as crosslinker. Contact angle and fluorescence measurements, X-ray photoelectron spectroscopy and infrared spectroscopy confirmed the surface modification. Here the highest functionalization was observed for the O2 plasma/APTES modification. Furthermore, biocompatibility studies demonstrated that the surface reactions have no negative influence, neither on the viability of L929 mouse fibroblasts, nor on primary or secondary hemostasis. Release studies showed that the immobilization of ASA and VEGF on the modified PCL surface via DSC is greatly improved compared to the adsorption-only reference. The advantage of DSC is that it immobilizes both bioactive substances via non-hydrolyzable and/or hydrolyzable covalent bonding. The highest ASA loading and cumulative release was detected using NH3 plasma-activated PCL samples. For VEGF, the O2 plasma/APTES-modified PCL samples were most efficient with regard to loading and cumulative release. In conclusion, both modifications are promising methods to optimize PCL as scaffold material for bioartificial vessel prostheses.


Assuntos
Bioprótese , Prótese Vascular , Teste de Materiais , Poliésteres/química , Tecidos Suporte/química , Animais , Linhagem Celular , Camundongos , Propriedades de Superfície
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...