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1.
Int J Mol Sci ; 22(8)2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33921304

RESUMO

Local basement membrane (BM) disruption marks the initial step of breast cancer invasion. The activation mechanisms of force-driven BM-weakening remain elusive. We studied the mechanical response of MCF10A-derived human breast cell acini with BMs of tuneable maturation to physical and soluble tumour-like extracellular matrix (ECM) cues. Traction force microscopy (TFM) and elastic resonator interference stress microscopy (ERISM) were used to quantify pro-invasive BM stress and protrusive forces. Substrate stiffening and mechanically impaired BM scaffolds induced the invasive transition of benign acini synergistically. Robust BM scaffolds attenuated this invasive response. Additional oncogenic EGFR activation compromised the BMs' barrier function, fuelling invasion speed and incidence. Mechanistically, EGFR-PI3-Kinase downstream signalling modulated both MMP- and force-driven BM-weakening processes. We show that breast acini form non-proteolytic and BM-piercing filopodia for continuous matrix mechanosensation, which significantly push and pull on the BM and ECM under pro-invasive conditions. Invasion-triggered acini further shear and compress their BM by contractility-based stresses that were significantly increased (3.7-fold) compared to non-invasive conditions. Overall, the highest amplitudes of protrusive and contractile forces accompanied the highest invasiveness. This work provides a mechanistic concept for tumour ECM-induced mechanically misbalanced breast glands fuelling force-driven BM disruption. Finally, this could facilitate early cell dissemination from pre-invasive lesions to metastasize eventually.


Assuntos
Mama/metabolismo , Fator de Crescimento Epidérmico/genética , Neoplasias/genética , Células Acinares/metabolismo , Células Acinares/patologia , Membrana Basal/metabolismo , Membrana Basal/patologia , Mama/patologia , Linhagem Celular Tumoral , Receptores ErbB/genética , Matriz Extracelular/genética , Matriz Extracelular/patologia , Feminino , Humanos , Glândulas Mamárias Humanas/patologia , Fenômenos Mecânicos , Invasividade Neoplásica/genética , Neoplasias/patologia , Pseudópodes/genética , Pseudópodes/patologia
2.
Polymers (Basel) ; 13(2)2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33477626

RESUMO

Local drug delivery has become indispensable in biomedical engineering with stents being ideal carrier platforms. While local drug release is superior to systemic administration in many fields, the incorporation of drugs into polymers may influence the physico-chemical properties of said matrix. This is of particular relevance as minimally invasive implantation is frequently accompanied by mechanical stresses on the implant and coating. Thus, drug incorporation into polymers may result in a susceptibility to potentially life-threatening implant failure. We investigated spray-coated poly-l-lactide (PLLA)/drug blends using thermal measurements (DSC) and tensile tests to determine the influence of selected drugs, namely sirolimus, paclitaxel, dexamethasone, and cyclosporine A, on the physico-chemical properties of the polymer. For all drugs and PLLA/drug ratios, an increase in tensile strength was observed. As for sirolimus and dexamethasone, PLLA/drug mixed phase systems were identified by shifted drug melting peaks at 200 °C and 240 °C, respectively, whereas paclitaxel and dexamethasone led to cold crystallization. Cyclosporine A did not affect matrix thermal properties. Altogether, our data provide a contribution towards an understanding of the complex interaction between PLLA and different drugs. Our results hold implications regarding the necessity of target-oriented thermal treatment to ensure the shelf life and performance of stent coatings.

3.
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.

4.
Pharmaceuticals (Basel) ; 13(9)2020 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-32961780

RESUMO

Breast cancer progression is marked by cancer cell invasion and infiltration, which can be closely linked to sites of tumor-connected basement membrane thinning, lesion, or infiltration. Bad treatment prognosis frequently accompanies lack of markers for targeted therapy, which brings traditional chemotherapy into play, despite its adverse effects like therapy-related toxicities. In the present work, we compared different liposomal formulations for the delivery of two anthracyclines, doxorubicin and aclacinomycin A, to a 2D cell culture and a 3D breast acini model. One formulation was the classical phospholipid liposome with a polyethylene glycol (PEG) layer serving as a stealth coating. The other formulation was fusogenic liposomes, a biocompatible, cationic, three-component system of liposomes able to fuse with the plasma membrane of target cells. For the lysosome entrapment-sensitive doxorubicin, membrane fusion enabled an increased anti-proliferative effect in 2D cell culture by circumventing the endocytic route. In the 3D breast acini model, this process was found to be limited to cells beneath a thinned or compromised basement membrane. In acini with compromised basement membrane, the encapsulation of doxorubicin in fusogenic liposomes increased the anti-proliferative effect of the drug in comparison to a formulation in PEGylated liposomes, while this effect was negligible in the presence of intact basement membranes.

5.
Pharmaceutics ; 11(12)2019 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-31817900

RESUMO

Here, we present a new hybrid additive manufacturing (AM) process to create drug delivery systems (DDSs) with selectively incorporated drug depots. The matrix of a DDS was generated by stereolithography (SLA), whereas the drug depots were loaded using inkjet printing. The novel AM process combining SLA with inkjet printing was successfully implemented in an existing SLA test setup. In the first studies, poly(ethylene glycol) diacrylate-based specimens with integrated depots were generated. As test liquids, blue and pink ink solutions were used. Furthermore, bovine serum albumin labeled with Coomassie blue dye as a model drug was successfully placed in a depot inside a DDS. The new hybrid AM process makes it possible to place several drugs independently of each other within the matrix. This allows adjustment of the release profiles of the drugs depending on the size as well as the position of the depots in the DDS.

6.
JAMA Ophthalmol ; 136(8): 849-856, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29879277

RESUMO

Importance: There are no approved drug treatments for autosomal dominant retinitis pigmentosa, a relentlessly progressive cause of adult and childhood blindness. Objectives: To evaluate the potential efficacy and assess the safety of orally administered valproic acid (VPA) in the treatment of autosomal dominant retinitis pigmentosa. Design, Setting, and Participants: Multicenter, phase 2, prospective, interventional, placebo-controlled, double-masked randomized clinical trial. The study took place in 6 US academic retinal degeneration centers. Individuals with genetically characterized autosomal dominant retinitis pigmentosa were randomly assigned to receive treatment or placebo for 12 months. Analyses were intention-to-treat. Interventions: Oral VPA 500 mg to 1000 mg daily for 12 months or placebo. Main Outcomes and Measures: The primary outcome measure was determined prior to study initiation as the change in visual field area (assessed by the III4e isopter, semiautomated kinetic perimetry) between baseline and month 12. Results: The mean (SD) age of the 90 participants was 50.4 (11.6) years. Forty-four (48.9%) were women, 87 (96.7%) were white, and 79 (87.8%) were non-Hispanic. Seventy-nine participants (87.8%) completed the study (42 [95.5%] received placebo and 37 [80.4%] received VPA). Forty-two (46.7%) had a rhodopsin mutation. Most adverse events were mild, although 7 serious adverse events unrelated to VPA were reported. The difference between the VPA and placebo arms for mean change in the primary outcome was -150.43 degree2 (95% CI, -290.5 to -10.03; P = .035). Conclusions and Relevance: This negative value indicates that the VPA arm had worse outcomes than the placebo group. This study brings to light the key methodological considerations that should be applied to the rigorous evaluation of treatments for these conditions. This study does not provide support for the use of VPA in the treatment of autosomal dominant retinitis pigmentosa. Trial Registration: ClinicalTrials.gov Identifier: NCT01233609.


Assuntos
Anticonvulsivantes/uso terapêutico , Retinite Pigmentosa/tratamento farmacológico , Ácido Valproico/uso terapêutico , Transtornos da Visão/tratamento farmacológico , Administração Oral , Adulto , Idoso , Anticonvulsivantes/administração & dosagem , Método Duplo-Cego , Eletrorretinografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Estudos Prospectivos , Retina/fisiopatologia , Retinite Pigmentosa/genética , Retinite Pigmentosa/fisiopatologia , Rodopsina/genética , Ácido Valproico/administração & dosagem , Transtornos da Visão/fisiopatologia , Acuidade Visual/fisiologia , Testes de Campo Visual , Campos Visuais/fisiologia
7.
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
8.
Materials (Basel) ; 11(3)2018 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-29495462

RESUMO

Silicones are widely used in medical applications. In ophthalmology, glaucoma drainage devices are utilized if conservative therapies are not applicable or have failed. Long-term success of these devices is limited by failure to control intraocular pressure due to fibrous encapsulation. Therefore, different medical approved silicones were tested in vitro for cell adhesion, cell proliferation and viability of human Sclera (hSF) and human Tenon fibroblasts (hTF). The silicones were analysed also depending on the sample preparation according to the manufacturer's instructions. The surface quality was characterized with environmental scanning electron microscope (ESEM) and water contact angle measurements. All silicones showed homogeneous smooth and hydrophobic surfaces. Cell adhesion was significantly reduced on all silicones compared to the negative control. Proliferation index and cell viability were not influenced much. For development of a new glaucoma drainage device, the silicones Silbione LSR 4330 and Silbione LSR 4350, in this study, with low cell counts for hTF and low proliferation indices for hSF, and silicone Silastic MDX4-4210, with low cell counts for hSF and low proliferation indices for hTF, have shown the best results in vitro. Due to the high cell adhesion shown on Silicone LSR 40, 40,026, this material is unsuitable.

9.
Materials (Basel) ; 11(1)2017 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-29267239

RESUMO

Metallic biomaterials are widely used in maxillofacial surgery. While titanium is presumed to be the gold standard, magnesium-based implants are a current topic of interest and investigation due to their biocompatible, osteoconductive and degradable properties. This study investigates the effects of poly-ε-caprolactone-coated and previtalised magnesium implants on osteointegration within murine calvarial bone defects: After setting a 3 mm × 3 mm defect into the calvaria of 40 BALB/c mice the animals were treated with poly-ε-caprolactone-coated porous magnesium implants (without previtalisation or previtalised with either osteoblasts or adipose derived mesenchymal stem cells), porous Ti6Al4V implants or without any implant. To evaluate bone formation and implant degradation, micro-computertomographic scans were performed at day 0, 28, 56 and 84 after surgery. Additionally, histological thin sections were prepared and evaluated histomorphometrically. The outcomes revealed no significant differences within the differently treated groups regarding bone formation and the amount of osteoid. While the implant degradation resulted in implant shifting, both implant geometry and previtalisation appeared to have positive effects on vascularisation. Although adjustments in degradation behaviour and implant fixation are indicated, this study still considers magnesium as a promising alternative to titanium-based implants in maxillofacial surgery in future.

10.
Materials (Basel) ; 10(12)2017 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-29168794

RESUMO

Titanium is widely used as a bone implant material due to its biocompatibility and high resilience. Since its Young's modulus differs from bone tissue, the resulting "stress shielding" could lead to scaffold loosening. However, by using a scaffold-shaped geometry, the Young's modulus can be adjusted. Also, a porous geometry enables vascularisation and bone ingrowth inside the implant itself. Additionally, growth factors can improve these effects. In order to create a deposit and release system for these factors, the titanium scaffolds could be coated with degradable polymers. Therefore, in the present study, synthetic poly-ε-caprolactone (PCL) and the biopolymer poly(3-hydroxybutyrate) (P(3HB)) were tested for coating efficiency, cell adhesion, and biocompatibility to find a suitable coating material. The underlying scaffold was created from titanium by Selective Laser Melting (SLM) and coated with PCL or P(3HB) via dip coating. To test the biocompatibility, Live Cell Imaging (LCI) as well as vitality and proliferation assays were performed. In addition, cell adhesion forces were detected via Single Cell Force Spectroscopy, while the coating efficiency was observed using environmental scanning electron microscopy (ESEM) and energy-dispersive X-ray (EDX) analyses. Regarding the coating efficiency, PCL showed higher values in comparison to P(3HB). Vitality assays revealed decent vitality values for both polymers, while values for PCL were significantly lower than those for blank titanium. No significant differences could be observed between PCL and P(3HB) in proliferation and cell adhesion studies. Although LCI observations revealed decreasing values in cell number and populated area over time on both polymer-coated scaffolds, these outcomes could be explained by the possibility of coating diluent residues accumulating in the culture medium. Overall, both polymers fulfill the requirements regarding biocompatibility. Nonetheless, since only PCL coating ensured the maintenance of the porous implant structure, it is preferable to be used as a coating material for creating a deposit and release system for growth factors.

11.
Ophthalmic Surg Lasers Imaging Retina ; 48(1): 26-32, 2017 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-28060391

RESUMO

BACKGROUND AND OBJECTIVE: The objective of this study was to compare visual acuity outcomes between the following procedures used to treat submacular hemorrhages: pneumatic displacement followed by intravitreal tissue plasminogen activator (tPA) if needed (pneumatic ± tPA) and pars plana vitrectomy (PPV) with subretinal tPA (PPV + tPA). PATIENTS AND METHODS: This is a retrospective chart review of submacular hemorrhages treated with either pneumatic ± tPA or PPV + tPA. RESULTS: Eighteen patients had pneumatic ± tPA, and 14 patients had PPV + tPA. The percentage of patients achieving three lines or greater of vision improvement 1 year postoperatively was 46% and 18% in these groups, respectively (P = .194). CONCLUSION: The difference in visual acuity was not statistically significant; however, the lack of a statistical difference is important as pneumatic ± tPA is a less-invasive, less costly procedure that can be done in a clinical setting. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:26-32.].


Assuntos
Hemorragia Retiniana/tratamento farmacológico , Ativador de Plasminogênio Tecidual/administração & dosagem , Acuidade Visual , Idoso , Feminino , Seguimentos , Humanos , Injeções , Injeções Intravítreas , Macula Lutea/patologia , Masculino , Retina , Hemorragia Retiniana/diagnóstico , Estudos Retrospectivos , Tomografia de Coerência Óptica , Resultado do Tratamento
12.
Materials (Basel) ; 9(4)2016 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-28773427

RESUMO

Implant constructs supporting angiogenesis are favorable for treating critically-sized bone defects, as ingrowth of capillaries towards the center of large defects is often insufficient. Consequently, the insufficient nutritional supply of these regions leads to impaired bone healing. Implants with specially designed angiogenic supporting geometry and functionalized with proangiogenic cytokines can enhance angiogenesis. In this study, Vascular Endothelial Growth Factor (VEGF) and High Mobility Group Box 1 (HMGB1) were used for incorporation into poly-ε-caprolactone (PCL)-coated porous titanium implants. Bioactivity of released factors and influence on angiogenesis of functionalized implants were evaluated using a migration assay and angiogenesis assays. Both implants released angiogenic factors, inducing migration of endothelial cells. Also, VEGF-functionalized PCL-coated titanium implants enhanced angiogenesis in vitro. Both factors were rapidly released in high doses from the implant coating during the first 72 h.

13.
Int J Mol Sci ; 17(1)2015 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-26703586

RESUMO

For healing of critically sized bone defects, biocompatible and angiogenesis supporting implants are favorable. Murine osteoblasts showed equal proliferation behavior on the polymers poly-ε-caprolactone (PCL) and poly-(3-hydroxybutyrate)/poly-(4-hydroxybutyrate) (P(3HB)/P(4HB)). As vitality was significantly better for PCL, it was chosen as a suitable coating material for further experiments. Titanium implants with 600 µm pore size were evaluated and found to be a good implant material for bone, as primary osteoblasts showed a vitality and proliferation onto the implants comparable to well bottom (WB). Pure porous titanium implants and PCL coated porous titanium implants were compared using Live Cell Imaging (LCI) with Green fluorescent protein (GFP)-osteoblasts. Cell count and cell covered area did not differ between the implants after seven days. To improve ingrowth of blood vessels into porous implants, proangiogenic factors like Vascular Endothelial Growth Factor (VEGF) and High Mobility Group Box 1 (HMGB1) were incorporated into PCL coated, porous titanium and magnesium implants. An angiogenesis assay was performed to establish an in vitro method for evaluating the impact of metallic implants on angiogenesis to reduce and refine animal experiments in future. Incorporated concentrations of proangiogenic factors were probably too low, as they did not lead to any effect. Magnesium implants did not yield evaluable results, as they led to pH increase and subsequent cell death.


Assuntos
Interface Osso-Implante/irrigação sanguínea , Magnésio/farmacologia , Neovascularização Fisiológica , Poliésteres/farmacologia , Titânio/farmacologia , Animais , Linhagem Celular , Células Cultivadas , Proteína HMGB1/farmacologia , Hidroxibutiratos/efeitos adversos , Hidroxibutiratos/farmacologia , Magnésio/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , Osseointegração , Osteoblastos/efeitos dos fármacos , Osteoblastos/fisiologia , Poliésteres/efeitos adversos , Porosidade , Titânio/efeitos adversos , Fator A de Crescimento do Endotélio Vascular/farmacologia
14.
PLoS One ; 10(12): e0142075, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26641662

RESUMO

PURPOSE: Drug-eluting stents (DES) based on permanent polymeric coating matrices have been introduced to overcome the in stent restenosis associated with bare metal stents (BMS). A further step was the development of DES with biodegradable polymeric coatings to address the risk of thrombosis associated with first-generation DES. In this study we evaluate the biocompatibility of biodegradable polymer materials for their potential use as coating matrices for DES or as materials for fully bioabsorbable vascular stents. MATERIALS AND METHODS: Five different polymers, poly(L-lactide) PLLA, poly(D,L-lactide) PDLLA, poly(L-lactide-co-glycolide) P(LLA-co-GA), poly(D,L-lactide-co-glycolide) P(DLLA-co-GA) and poly(L-lactide-co-ε-caprolactone), P(LLA-co-CL) were examined in vitro without and with surface modification. The surface modification of polymers was performed by means of wet-chemical (NaOH and ethylenediamine (EDA)) and plasma-chemical (O2 and NH3) processes. The biocompatibility studies were performed on three different cell types: immortalized mouse fibroblasts (cell line L929), human coronary artery endothelial cells (HCAEC) and human umbilical vein endothelial cells (HUVEC). The biocompatibility was examined quantitatively using in vitro cytotoxicity assay. Cells were investigated immunocytochemically for expression of specific markers, and morphology was visualized using confocal laser scanning (CLSM) and scanning electron (SEM) microscopy. Additionally, polymer surfaces were examined for their thrombogenicity using an established hemocompatibility test. RESULTS: Both endothelial cell types exhibited poor viability and adhesion on all five unmodified polymer surfaces. The biocompatibility of the polymers could be influenced positively by surface modifications. In particular, a reproducible effect was observed for NH3-plasma treatment, which enhanced the cell viability, adhesion and morphology on all five polymeric surfaces. CONCLUSION: Surface modification of polymers can provide a useful approach to enhance their biocompatibility. For clinical application, attempts should be made to stabilize the plasma modification and use it for coupling of biomolecules to accelerate the re-endothelialization of stent surfaces in vivo.


Assuntos
Materiais Biocompatíveis/administração & dosagem , Materiais Biocompatíveis/química , Polímeros/administração & dosagem , Polímeros/química , Propriedades de Superfície/efeitos dos fármacos , Trombose/induzido quimicamente , Animais , Linhagem Celular , Vasos Coronários/efeitos dos fármacos , Stents Farmacológicos/efeitos adversos , Fibroblastos/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Camundongos , Stents/efeitos adversos
15.
Int J Mol Sci ; 16(6): 13287-301, 2015 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-26068455

RESUMO

Degradable implant material for bone remodeling that corresponds to the physiological stability of bone has still not been developed. Promising degradable materials with good mechanical properties are magnesium and magnesium alloys. However, excessive gas production due to corrosion can lower the biocompatibility. In the present study we used the polymer coating polycaprolactone (PCL), intended to lower the corrosion rate of magnesium. Additionally, improvement of implant geometry can increase bone remodeling. Porous structures are known to support vessel ingrowth and thus increase osseointegration. With the selective laser melting (SLM) process, defined open porous structures can be created. Recently, highly reactive magnesium has also been processed by SLM. We performed studies with a flat magnesium layer and with porous magnesium implants coated with polymers. The SLM produced magnesium was compared with the titanium alloy TiAl6V4, as titanium is already established for the SLM-process. For testing the biocompatibility, we used primary murine osteoblasts. Results showed a reduced corrosion rate and good biocompatibility of the SLM produced magnesium with PCL coating.


Assuntos
Interface Osso-Implante , Materiais Revestidos Biocompatíveis/efeitos adversos , Magnésio/química , Poliésteres/química , Titânio/química , Animais , Células Cultivadas , Materiais Revestidos Biocompatíveis/química , Lasers , Magnésio/efeitos adversos , Camundongos , Osseointegração , Titânio/efeitos adversos
16.
Int J Mol Sci ; 16(4): 7478-92, 2015 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-25849656

RESUMO

To improve well-known titanium implants, pores can be used for increasing bone formation and close bone-implant interface. Selective Laser Melting (SLM) enables the production of any geometry and was used for implant production with 250-µm pore size. The used pore size supports vessel ingrowth, as bone formation is strongly dependent on fast vascularization. Additionally, proangiogenic factors promote implant vascularization. To functionalize the titanium with proangiogenic factors, polycaprolactone (PCL) coating can be used. The following proangiogenic factors were examined: vascular endothelial growth factor (VEGF), high mobility group box 1 (HMGB1) and chemokine (C-X-C motif) ligand 12 (CXCL12). As different surfaces lead to different cell reactions, titanium and PCL coating were compared. The growing into the porous titanium structure of primary osteoblasts was examined by cross sections. Primary osteoblasts seeded on the different surfaces were compared using Live Cell Imaging (LCI). Cross sections showed cells had proliferated, but not migrated after seven days. Although the cell count was lower on titanium PCL implants in LCI, the cell count and cell spreading area development showed promising results for titanium PCL implants. HMGB1 showed the highest migration capacity for stimulating the endothelial cell line. Future perspective would be the incorporation of HMGB1 into PCL polymer for the realization of a slow factor release.


Assuntos
Vasos Sanguíneos/efeitos dos fármacos , Neovascularização Fisiológica/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Titânio/administração & dosagem , Animais , Vasos Sanguíneos/metabolismo , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Quimiocina CXCL12/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Congelamento , Proteína HMGB1/metabolismo , Lasers , Camundongos , Camundongos Endogâmicos C57BL , Osteoblastos/metabolismo , Poliésteres/química , Polímeros/química , Porosidade , Próteses e Implantes , Propriedades de Superfície , Fator A de Crescimento do Endotélio Vascular/metabolismo
17.
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
18.
Biomacromolecules ; 14(11): 3985-96, 2013 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-24088140

RESUMO

Novel biodegradable materials with tunable hydrolytic degradation rate are prepared by grafting of phosphonoethylated polyglycidols with polyesters. First, the hydrolytically degradable polyester grafts are attached to polyglycidols partially grafted with phosphonoethylated diethyl esters through chemical-catalyzed grafting using tin(II) octanoate, then the diethyl ester groups are chemoselectively converted to the corresponding monoester (mixed phosphonate/phosphonic acid) using alkali metal halides. The products are characterized by means of (1)H, (13)C, and (31)P NMR spectroscopy, as well as size-exclusion chromatography and differential scanning calorimetry. The in vitro degradation of the copolymers is studied in phosphate buffered solution at 55 °C. The copolymers are of the same architecture, molecular weight, and crystallinity, only differing in the pendant phosphonate and mixed phosphonate/phosphonic acid groups, respectively. On the basis of mass loss, decrease of the molecular weight, and morphological analysis of the copolymers, the strong impact of mixed phosphonate/phosphonic acid groups on the hydrolytic degradation rate is demonstrated.


Assuntos
Ésteres/química , Poliésteres/química , Propilenoglicóis/química , Animais , Fibroblastos , Hidrólise , Camundongos , Estrutura Molecular , Propilenoglicóis/síntese química
19.
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
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