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To carry out the preclinical and histological evaluation of a novel nanotechnology-based microshunt for drainage glaucoma surgery. Twelve New Zealand White rabbits were implanted with a novel microshunt and followed up for 6 weeks. The new material composite consists of the silicone polydimethylsiloxane (PDMS) and tetrapodal Zinc Oxide (ZnO-T) nano-/microparticles. The microshunts were inserted ab externo to connect the subconjunctival space with the anterior chamber. Animals were euthanized after 2 and 6 weeks for histological evaluation. Ocular health and implant position were assessed at postoperative days 1, 3, 7 and twice a week thereafter by slit lamp biomicroscopy. Intraocular pressure (IOP) was measured using rebound tonometry. A good tolerability was observed in both short- and medium-term follow-up. Intraocular pressure was reduced following surgery but increased to preoperative levels after 2 weeks. No clinical or histological signs of inflammatory or toxic reactions were seen; the fibrotic encapsulation was barely noticeable after two weeks and very mild after six weeks. The new material composite PDMS/ZnO-T is well tolerated and the associated foreign body fibrotic reaction quite mild. The new microshunt reduces the IOP for 2 weeks. Further research will elucidate a tube-like shape to improve and prolong outflow performance and longer follow-up to exclude medium-term adverse effects.
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Implantes para Drenagem de Glaucoma , Glaucoma , Óxido de Zinco , Animais , Coelhos , Implantes para Drenagem de Glaucoma/efeitos adversos , Glaucoma/cirurgia , Glaucoma/etiologia , Pressão Intraocular , Tonometria Ocular , Câmara Anterior/cirurgia , NanotecnologiaRESUMO
The glaucoma burden increases continuously and is estimated to affect more than 100 million people by 2040. As there is currently no cure to restore the optic nerve damage caused by glaucoma, the only controllable parameter is the intraocular pressure (IOP). In recent years, minimally invasive glaucoma surgery (MIGS) has emerged as an alternative to traditional treatments. It uses micro-sized drainage stents that are inserted through a small incision, minimizing the trauma to the tissue and reducing surgical and postoperative recovery time. However, a major challenge for MIGS devices is foreign body reaction and fibrosis, which can lead to a complete failure of the device. In this work, the antifibrotic potential of tetrapodal ZnO (t-ZnO) microparticles used as an additive is elucidated by using rat embryonic fibroblasts as a model. A simple, direct solvent-free process for the fabrication of stents with an outer diameter of 200-400 µm is presented, in which a high amount of t-ZnO particles (45-75 wt %) is mixed into polydimethylsiloxane (PDMS) and a highly viscous polymer/particle mixture is extruded. The fabricated stents possess increased elastic modulus compared to pure PDMS while remaining flexible to adapt to the curvature of an eye. In vitro experiments showed that the fibroblast cell viability was inhibited to 43 ± 3% when stents with 75 wt % t-ZnO were used. The results indicate that cell inhibiting properties can be attributed to an increased amount of protruding t-ZnO particles on the stent surface, leading to an increase in local contacts with cells and a disruption of the cell membrane. As a secondary mechanism, the released Zn ions could also contribute to the cell-inhibiting properties in the close vicinity of the stent surface. Overall, the fabrication method and the antifibrotic and mechanical properties of developed stents make them promising for application in MIGS.
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Glaucoma , Stents , Glaucoma/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Animais , Ratos , Óxido de ZincoRESUMO
Glaucoma filtering surgery is applied to reduce intraocular pressure (IOP) in cases of uncontrolled glaucoma. However, postoperative fibrosis reduces the long-term success of both standard trabeculectomy and microstents. The aim of this study was to test the antiproliferative and anti-inflammatory potential of ZnO-tetrapods (ZnO-T) on human Tenon's fibroblasts (HTFs) for glaucoma surgery. The toxicity of ZnO-T on HTFs was determined using an MTT test. For analysis of fibroblast proliferation, migration, and transdifferentiation, cultures were stained for Ki67, alpha-smooth muscle actin (α-SMA), and p-SMAD. A fully quantitative multiplex ELISA was used to determine the concentrations of different cytokines, platelet-derived growth factor (PDGF), and hepatocyte growth factor (HGF) in culture supernatants with and without previous ZnO-T treatment. Treatment with higher concentrations (10 and 20 µg/mL) was associated with HTF toxicity, as shown in the wound healing assay. Furthermore, the number of Ki67, α-SMA-positive, and pSMAD-positive cells, as well as IL-6 and HGF in supernatants, were significantly reduced following incubation with ZnO-T. In conclusion, we were able to show the antiproliferative and anti-inflammatory potentials of ZnO-T. Therefore, the use of ZnO-T may provide a new approach to reducing postoperative fibrosis in glaucoma filtering surgery.
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In our previous study we were able to show that zinc oxide (ZnO) tetrapods inhibit wound healing processes. Therefore, the aim of this study was to test the antiproliferative effect of two types of porous polydimethylsiloxane (PDMS)/ tetrapodal zinc oxide (ZnO-T) materials, as well as their usability for glaucoma implants. To find the best implant material, two different porous PDMS/ZnO-T materials were examined. One consisted of 3D interconnected PDMS coarse-pored foams with protruding ZnO-T particles; the other consisted of fine-pored 3D interconnected ZnO-T networks homogeneously coated by a thin PDMS film in the nanometer range. Fibroblast cell viability was investigated for both materials via MTT dye, and some implant material samples were further processed for electron microscopy. Both PDMS/ZnO-T materials showed reduced cell viability in the MTT staining. Furthermore, the electron microscopy revealed barely any fibroblasts growing on the implant materials. At the surface of the fine-pored implant material, however, fibroblasts could not be observed in the etched control samples without ZnO-T. It was found that post-processing of the material to the final stent diameter was highly challenging and that the fabrication method, therefore, had to be adapted. In conclusion, we were able to demonstrate the antiproliferative potential of the two different PDMS/ZnO-T materials. Furthermore, smaller pore size (in the range of tens of micrometers) in the implant material seems to be preferable.
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Tetrapodal zinc oxide (t-ZnO) is used to fabricate polymer composites for many different applications ranging from biomedicine to electronics. In recent times, macroscopic framework structures from t-ZnO have been used as a versatile sacrificial template for the synthesis of multi-scaled foam structures from different nanomaterials such as graphene, hexagonal boron nitride or gallium nitride. Many of these fabrication methods rely on wet-chemical coating processes using nanomaterial dispersions, leading to a strong interest in the actual coating mechanism and factors influencing it. Depending on the type of medium (e.g. solvent) used, different results regarding the homogeneity of the nanomaterial coating can be achieved. In order to understand how a medium influences the coating behavior, the evaporation process of water and ethanol is investigated in this work using in situ synchrotron radiation-based micro computed tomography (SRµCT). By employing propagation-based phase contrast imaging, both the t-ZnO network and the medium can be visualized. Thus, the evaporation process can be monitored non-destructively in three dimensions. This investigation showed that using a polar medium such as water leads to uniform evaporation and, by that, a homogeneous coating of the entire network.
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Active hybrid composites represent a novel class of smart materials used to design morphing surfaces, opening up new applications in the aircraft and automotive industries. The bending of the active hybrid composite is induced by the contraction of electrically activated shape memory alloy (SMA) wires, which are placed with an offset to the neutral axis of the composite. Therefore, the adhesion strength between the SMA wire and the surrounding polymer matrix is crucial to the load transfer and the functionality of the composite. Thus, the interface adhesion strength is of great importance for the performance and the actuation potential of active hybrid composites. In this work, the surface of a commercially available one-way effect NiTi SMA wire with a diameter of 1 mm was structured by selective electrochemical etching that preferably starts at defect sites, leaving the most thermodynamically stable surfaces of the wire intact. The created etch pits lead to an increase in the surface area of the wire and a mechanical interlocking with the polymer, resulting in a combination of adhesive and cohesive failure modes after a pull-out test. Consequently, the force of the first failure determined by an optical stress measurement was increased by more than 3 times when compared to the as-delivered SMA wire. The actuation characterization test showed that approximately the same work capacity could be retrieved from structured SMA wires. Moreover, structured SMA wires exhibited the same shape of the stress-strain curve as the as-delivered SMA wire, and the mechanical performance was not influenced by the structuring process. The austenite start As and austenite finish Af transformation temperatures were also not found to be affected by the structuring process. The formation of etching pits with different geometries and densities was discussed with regard to the kinetics of oxide formation and dissolution.
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In this study, polydimethylsiloxane (PDMS)/polythiourethane (PTU) composite reinforced with tetrapodal shaped micro-nano ZnO particles (t-ZnO) was successfully produced by a versatile, industrially applicable polymer blending process. On the surface of this composite, PDMS is distributed in the form of microdomains embedded in a PTU matrix. The composite inherited not only good mechanical properties originating from PTU but also promising fouling-release (FR) properties due to the presence of PDMS on the surface. It was shown that the preferential segregation of PDMS domains at the polymer/air interface could be attributed to the difference in the surface free energy of PDMS and PTU. The PDMS microdomains at the PTU/air interface significantly reduced the barnacle adhesion strength on the composite. Both the pseudo- and natural barnacle adhesion strength on the composite was approximately 0.1 MPa, similar to that on pure PDMS. The pseudo-barnacle adhesion on reference surfaces AlMg3 and PTU reached approximately 4 and 6 MPa, respectively. Natural barnacles could not be removed intact from AlMg3 and PTU surfaces without breaking the shell, indicating that the adhesion strength was higher than the mechanical strength of a barnacle shell (approximately 0.4 MPa). The integrity of PDMS microdomains was maintained after 12 months of immersion in seawater and barnacle removal. No surface deteriorations were found. In short, the composite showed excellent potential as a long-term stable FR coating for marine applications.
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Incrustação Biológica/prevenção & controle , Dimetilpolisiloxanos/química , Poliuretanos/química , Thoracica/citologia , Óxido de Zinco/química , Ar/análise , Animais , Nanopartículas/química , Transição de Fase , Propriedades de SuperfícieRESUMO
The attachment of bacteria and other microbes to natural and artificial surfaces leads to the development of biofilms, which can further cause nosocomial infections. Thus, an important field of research is the development of new materials capable of preventing the initial adhesion of pathogenic microorganisms. In this work, novel polymer/particle composite materials, based on a polythiourethane (PTU) matrix and either spherical (s-ZnO) or tetrapodal (t-ZnO) shaped ZnO fillers, were developed and characterized with respect to their mechanical, chemical and surface properties. To then evaluate their potential as anti-fouling surfaces, the adhesion of two different pathogenic microorganism species, Staphylococcus aureus and Candida glabrata, was studied using atomic force microscopy (AFM). Our results show that the adhesion of both S. aureus and C. glabrata to PTU and PTU/ZnO is decreased compared to a model surface polydimethylsiloxane (PDMS). It was furthermore found that the amount of both s-ZnO and t-ZnO filler had a direct influence on the adhesion of S. aureus, as increasing amounts of ZnO particles resulted in reduced adhesion of the cells. For both microorganisms, material composites with 5 wt.% of t-ZnO particles showed the greatest potential for anti-fouling with significantly decreased adhesion of cells. Altogether, both pathogens exhibit a reduced capacity to adhere to the newly developed nanomaterials used in this study, thus showing their potential for bio-medical applications.
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Ecological considerations strongly necessitate the development of environmentally friendly antifouling paints. A promising alternative to biocide containing antifouling paints are fouling-release coatings, which are non-toxic and designed to prevent permanent attachment of marine organisms to the surface, due to their low surface energy. However, these coatings suffer from insufficient mechanical properties, which make them unsuitable for mechanically stressed surfaces e.g., on ship hulls. To overcome those obstacles, polydimethylsiloxane (PDMS)-polythiourethane (PTU) composites modified with tetrapodal shaped micro-nano ZnO particles (t-ZnO) were produced and characterized by evaluating the surface energy, mechanical properties, and fouling-release performance. Among all variations, PTU/1 wt.% PDMS composites with 1 wt.% t-ZnO particles possess superior properties for applications as fouling-release coatings for maritime purposes.