Microneedles pierce the epidermis to create micro-channels for drug delivery in a painless and minimally invasive way. With these micro-channels, large macromolecules can penetrate through the complex barriers of skin to reach the target tissue. Cell therapy delivers cells to repair or replace damaged tissue and generally involves direct injection into the tissue. But it has drawbacks, such as the risk of infection, low patient compliance due to pain at injection, leakage of cell suspensions from the injection site and cell damage during injection. Hollow microneedle arrays with various microstructures are successfully fabricated by micromolding, where their microstructure can be controlled by the laser power and the drawing pattern. The cells are easily loaded on top of hollow microneedles. The results show that PMMA hollow microneedles have good biocompatibility and the cells can be successfully delivered to the acellular tissue. This study confirms that the cells can be effectively delivered and penetrate into tissue by a hollow microneedle patch. The delivered cells proliferate and distribute evenly in the tissue. Hollow microneedles provide a minimally invasive route for effectively delivering cells into tissue. This novel strategy has potential application for cell therapy.
{"title":"Fabrication of Hollow Microneedle Patch With Controllable Microstructure for Cell Therapy","authors":"Ying-Hou Chen, Fang-Ying Wang, Yong-Shi Chan, Yi-You Huang","doi":"10.2139/ssrn.3757907","DOIUrl":"https://doi.org/10.2139/ssrn.3757907","url":null,"abstract":"Microneedles pierce the epidermis to create micro-channels for drug delivery in a painless and minimally invasive way. With these micro-channels, large macromolecules can penetrate through the complex barriers of skin to reach the target tissue. Cell therapy delivers cells to repair or replace damaged tissue and generally involves direct injection into the tissue. But it has drawbacks, such as the risk of infection, low patient compliance due to pain at injection, leakage of cell suspensions from the injection site and cell damage during injection. Hollow microneedle arrays with various microstructures are successfully fabricated by micromolding, where their microstructure can be controlled by the laser power and the drawing pattern. The cells are easily loaded on top of hollow microneedles. The results show that PMMA hollow microneedles have good biocompatibility and the cells can be successfully delivered to the acellular tissue. This study confirms that the cells can be effectively delivered and penetrate into tissue by a hollow microneedle patch. The delivered cells proliferate and distribute evenly in the tissue. Hollow microneedles provide a minimally invasive route for effectively delivering cells into tissue. This novel strategy has potential application for cell therapy.","PeriodicalId":119194,"journal":{"name":"MatSciRN: Other Structural Materials (Topic)","volume":"3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125546089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
High intensity electric and magnetic fields produced by lightning discharge can penetrate through any structure in its vicinity. Installation of a sensitive component inside any structure complying the Electromagnetic Compatibility standards need the information of exposure limit of the equipment in the installation environment. Any structure provides natural shielding to electromagnetic field and its limit depends on the material properties. In addition the structure dimension plays key role in defining the limit of shielding. This paper investigates the effect of aperture on the shielding effectiveness of building structure made of construction material against lightning electromagnetic fields. Building structures constructed in computer aided design (CAD) tool, are subjected to lighting electromagnetic field in FEKO Electromagnetic simulation software. Time domain approach is used to compute the shielding effectives of the building for different structural variations. It is seen that apertures decrease the shielding effectiveness of the building . As the structure size increases the percentage decrease in shielding effectiveness due to the presence of aperture increases. For magnetic field, construction material does not provide considerable shielding.
{"title":"Time Domain Analysis of the Effect of Apertures on the Shielding Effectiveness of Buildings","authors":"A. V, S. K., Ravishankar K","doi":"10.2139/ssrn.3790208","DOIUrl":"https://doi.org/10.2139/ssrn.3790208","url":null,"abstract":"High intensity electric and magnetic fields produced by lightning discharge can penetrate through any structure in its vicinity. Installation of a sensitive component inside any structure complying the Electromagnetic Compatibility standards need the information of exposure limit of the equipment in the installation environment. Any structure provides natural shielding to electromagnetic field and its limit depends on the material properties. In addition the structure dimension plays key role in defining the limit of shielding. This paper investigates the effect of aperture on the shielding effectiveness of building structure made of construction material against lightning electromagnetic fields. Building structures constructed in computer aided design (CAD) tool, are subjected to lighting electromagnetic field in FEKO Electromagnetic simulation software. Time domain approach is used to compute the shielding effectives of the building for different structural variations. It is seen that apertures decrease the shielding effectiveness of the building . As the structure size increases the percentage decrease in shielding effectiveness due to the presence of aperture increases. For magnetic field, construction material does not provide considerable shielding.","PeriodicalId":119194,"journal":{"name":"MatSciRN: Other Structural Materials (Topic)","volume":"28 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130689665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-10-23DOI: 10.15587/1729-4061.2020.213525
J. Luchko, V. Kovalchuk, I. Kravets, O. Gajda, A. Onyshchenko
The technical condition of the railroad track subgrade has been analyzed, as well as the issues related to ensuring its strength and stability when exposed to floodwaters and when the track's sections are overmoistened during operation. As a result, it has been established that it is necessary to develop methods aimed at improving the subgrade's carrying capacity. The georadar research has explored the problematic areas of the railroad track subgrade, based on which the distribution of subgrade heterogeneity in the vertical plane, as well as the boundaries of its location, were established. Therefore, georadar research makes it possible to detect hidden defective sites in the subgrade without disrupting its strength characteristics. A technique has been proposed to improve the carrying capacity of the failed subgrade of a railroad track using the combined arrangement of drainage pipes in the vertical and horizontal directions in the railroad embankment. The special feature of this technique is the possibility to drain water at the different levels of surface water, which provides for an increase in the carrying capacity of the failed subgrade. The strained-deformed state of the subgrade reinforced with tubular drainage has been investigated. The result has proven the effectiveness of the use of tubular drainages to improve the carrying capacity of the railroad track overmoistened subgrade exposed to constant and temporary loads. This study findings have established that the deformity of the subgrade increases when using tubular drainage, though this occurs only in the initial period of its arrangement, in further operation, when it removes water from the subgrade body, the carrying capacity of the subgrade, on the contrary, will improve due to the enhanced physical and mechanical properties of soils
{"title":"Determining Patterns in the Stressed Deformed State of the Railroad Track Subgrade Reinforced With Tubular Drains","authors":"J. Luchko, V. Kovalchuk, I. Kravets, O. Gajda, A. Onyshchenko","doi":"10.15587/1729-4061.2020.213525","DOIUrl":"https://doi.org/10.15587/1729-4061.2020.213525","url":null,"abstract":"The technical condition of the railroad track subgrade has been analyzed, as well as the issues related to ensuring its strength and stability when exposed to floodwaters and when the track's sections are overmoistened during operation. As a result, it has been established that it is necessary to develop methods aimed at improving the subgrade's carrying capacity. The georadar research has explored the problematic areas of the railroad track subgrade, based on which the distribution of subgrade heterogeneity in the vertical plane, as well as the boundaries of its location, were established. Therefore, georadar research makes it possible to detect hidden defective sites in the subgrade without disrupting its strength characteristics. A technique has been proposed to improve the carrying capacity of the failed subgrade of a railroad track using the combined arrangement of drainage pipes in the vertical and horizontal directions in the railroad embankment. The special feature of this technique is the possibility to drain water at the different levels of surface water, which provides for an increase in the carrying capacity of the failed subgrade. The strained-deformed state of the subgrade reinforced with tubular drainage has been investigated. The result has proven the effectiveness of the use of tubular drainages to improve the carrying capacity of the railroad track overmoistened subgrade exposed to constant and temporary loads. This study findings have established that the deformity of the subgrade increases when using tubular drainage, though this occurs only in the initial period of its arrangement, in further operation, when it removes water from the subgrade body, the carrying capacity of the subgrade, on the contrary, will improve due to the enhanced physical and mechanical properties of soils","PeriodicalId":119194,"journal":{"name":"MatSciRN: Other Structural Materials (Topic)","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129227306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-08-31DOI: 10.15587/1729-4061.2020.208940
A. Kondratiev, Oksana Prontsevych
Reducing the surface mass of an adhesive is one of the most important means to improve the perfection of cellular structures. One of the promising technologies in this respect is the addressed application of the adhesive on the ends of the cells. This technology excludes the passive mass of the glue that fills the intercellular surface, which is not involved in ensuring the bearing capability of the adhesive connection. However, a decrease in the glue application leads to a decrease in the bearing capability of a product. Therefore, reliable estimation methods are required to determine the bearing capability of such structures under the conditions of detaching the sheathing prior to experimental test. This work determines a mechanism of destruction of cellular structures under transversal loading depending on their parameters and factors of the technological process of addresses gluing. We have devised a method to analyze the bearing capability of the adhesive connection between a cellular filler and the carrying sheathing at the addressed glue application on the ends of the honeycombs. The method makes it possible to predict the character of their destruction depending on the relative depth of the penetration of the flange facets of a cellular filler into the melt adhesive. A modified mathematical model of the adhesive fillet has been synthesized, which takes into consideration the heterogeneity of glued materials and the existence of a gap between the ends of the facets of honeycombs and the bearing sheathing. A finite element method was used to obtain a rather complicated character of stress distribution in the zone of an adhesive fillet cross-section. We have drawn a practical conclusion that it is necessary to glue the sandwich structures of the examined type at a temperature and pressure that ensure the relative depth of the penetration of honeycombs' ends into the adhesive exceeding 50 %. Such technological parameters at the modern level of production of cellular products would help increase their weight perfection and achieve a certain economy of energy resources, used in the process of assembling-gluing the structures of the examined type
{"title":"Analysis of the Bearing Capacity of An Adhesive Connection between a Cellular Filler and Sheathing at the Addressed Application of the Adhesive onto the Ends of Honeycombs","authors":"A. Kondratiev, Oksana Prontsevych","doi":"10.15587/1729-4061.2020.208940","DOIUrl":"https://doi.org/10.15587/1729-4061.2020.208940","url":null,"abstract":"Reducing the surface mass of an adhesive is one of the most important means to improve the perfection of cellular structures. One of the promising technologies in this respect is the addressed application of the adhesive on the ends of the cells. This technology excludes the passive mass of the glue that fills the intercellular surface, which is not involved in ensuring the bearing capability of the adhesive connection. However, a decrease in the glue application leads to a decrease in the bearing capability of a product. Therefore, reliable estimation methods are required to determine the bearing capability of such structures under the conditions of detaching the sheathing prior to experimental test. This work determines a mechanism of destruction of cellular structures under transversal loading depending on their parameters and factors of the technological process of addresses gluing. We have devised a method to analyze the bearing capability of the adhesive connection between a cellular filler and the carrying sheathing at the addressed glue application on the ends of the honeycombs. The method makes it possible to predict the character of their destruction depending on the relative depth of the penetration of the flange facets of a cellular filler into the melt adhesive. A modified mathematical model of the adhesive fillet has been synthesized, which takes into consideration the heterogeneity of glued materials and the existence of a gap between the ends of the facets of honeycombs and the bearing sheathing. A finite element method was used to obtain a rather complicated character of stress distribution in the zone of an adhesive fillet cross-section. We have drawn a practical conclusion that it is necessary to glue the sandwich structures of the examined type at a temperature and pressure that ensure the relative depth of the penetration of honeycombs' ends into the adhesive exceeding 50 %. Such technological parameters at the modern level of production of cellular products would help increase their weight perfection and achieve a certain economy of energy resources, used in the process of assembling-gluing the structures of the examined type","PeriodicalId":119194,"journal":{"name":"MatSciRN: Other Structural Materials (Topic)","volume":"52 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131848774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-02-24DOI: 10.15587/1729-4061.2020.192680
S. Pozdieiev, K. Myhalenko, Vitaliy Nuianzin, O. Zemlianskyi, T. Kostenko
Explosive concentrations of various substances can accumulate inside industrial premises. In the presence of a sufficient amount of oxygen and an ignition source, such a situation could lead to explosion that may result in the destruction of building structures and the building in general. Strengthening the stability of supporting structures is aimed at protecting industrial premises against possible destruction by explosion indoors. One of the effective ways to protect construction structures against the excessive pressure of explosion is to use explosion venting panels. In order to solve practical tasks on protecting industrial premises and structures against explosion, one must be able to choose both the area and parameters for explosion venting panels. In addition, in order to reduce the related loads to safe quantities, it is necessary to properly calculate the bearing structures in terms of dynamic stability while maintaining their carrying capacity. The set task to ensure protection against explosion by applying explosion venting panels with flexible elements can be solved through integrated accounting for mechanical properties of cellular polycarbonate sheets. We have performed experimental research into performance of the inertia-free explosion venting panels with flexible enclosing elements exposed to dynamic loads under conditions of explosion. Based on the obtained results, the effective rigidity and critical displacement of cellular polycarbonate sheets of flexible elements have been determined. It has been established that for cellular polycarbonate sheets with a thickness of 4‒8 mm effective rigidity ranges within 301–215 N·m; the critical displacement of edges in this case is 2.9–9.8 mm. A mathematical model has been proposed that takes into consideration the influence of geometric dimensions and the critical value of deflection in a polycarbonate sheet as the flexible element of fencing on the operational conditions for explosion venting panels
{"title":"Revealing Patterns of the Effective Mechanical Characteristics of Cellular Sheet Poly-Carbonate for Explosion Venting Panels","authors":"S. Pozdieiev, K. Myhalenko, Vitaliy Nuianzin, O. Zemlianskyi, T. Kostenko","doi":"10.15587/1729-4061.2020.192680","DOIUrl":"https://doi.org/10.15587/1729-4061.2020.192680","url":null,"abstract":"Explosive concentrations of various substances can accumulate inside industrial premises. In the presence of a sufficient amount of oxygen and an ignition source, such a situation could lead to explosion that may result in the destruction of building structures and the building in general. Strengthening the stability of supporting structures is aimed at protecting industrial premises against possible destruction by explosion indoors. One of the effective ways to protect construction structures against the excessive pressure of explosion is to use explosion venting panels. In order to solve practical tasks on protecting industrial premises and structures against explosion, one must be able to choose both the area and parameters for explosion venting panels. In addition, in order to reduce the related loads to safe quantities, it is necessary to properly calculate the bearing structures in terms of dynamic stability while maintaining their carrying capacity. The set task to ensure protection against explosion by applying explosion venting panels with flexible elements can be solved through integrated accounting for mechanical properties of cellular polycarbonate sheets. We have performed experimental research into performance of the inertia-free explosion venting panels with flexible enclosing elements exposed to dynamic loads under conditions of explosion. Based on the obtained results, the effective rigidity and critical displacement of cellular polycarbonate sheets of flexible elements have been determined. It has been established that for cellular polycarbonate sheets with a thickness of 4‒8 mm effective rigidity ranges within 301–215 N·m; the critical displacement of edges in this case is 2.9–9.8 mm. A mathematical model has been proposed that takes into consideration the influence of geometric dimensions and the critical value of deflection in a polycarbonate sheet as the flexible element of fencing on the operational conditions for explosion venting panels","PeriodicalId":119194,"journal":{"name":"MatSciRN: Other Structural Materials (Topic)","volume":"32 46","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134412469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This paper presents a statistical analysis of Structural Steel to study the special effects of process constraints (Laser Power, Scan Speed, Spot Diameters and Heat flow diameter). These process parameters are taken as input changeable and twisting angle or deformation considered as the output variable. An Ansys 18.1 licensed software tool is used for modelling and optimization of the laser bending method. The performance of the developed model and results is matched and checked with reference papers. All the process parameters are investigated and set up considerable effect on the bending angle. The effect of the beam diameter, scan speed and heat flow energy on bending angle also compare with research papers. The bending angle enhanced with an increase in beam diameter at stable heat energy but decreased with increase in heat energy at constant beam diameter. The bending angle is also affected by overlapping and gap between beam diameters.
{"title":"Study and Validation of Laser Forming Process Numerical Models","authors":"Rizwan, C. Paul","doi":"10.2139/ssrn.3350998","DOIUrl":"https://doi.org/10.2139/ssrn.3350998","url":null,"abstract":"This paper presents a statistical analysis of Structural Steel to study the special effects of process constraints (Laser Power, Scan Speed, Spot Diameters and Heat flow diameter). These process parameters are taken as input changeable and twisting angle or deformation considered as the output variable. An Ansys 18.1 licensed software tool is used for modelling and optimization of the laser bending method. The performance of the developed model and results is matched and checked with reference papers. All the process parameters are investigated and set up considerable effect on the bending angle. The effect of the beam diameter, scan speed and heat flow energy on bending angle also compare with research papers. The bending angle enhanced with an increase in beam diameter at stable heat energy but decreased with increase in heat energy at constant beam diameter. The bending angle is also affected by overlapping and gap between beam diameters.","PeriodicalId":119194,"journal":{"name":"MatSciRN: Other Structural Materials (Topic)","volume":"14 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132699304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Autohydrolysis or self-hydrolysis or hydrothermal treatment of lignocellulosic materials like sawdust and straw is already used in bioethanol industry for water soluble fermentable sugars production. The main idea in this paper is the use of the autohydrolysis and other thermochemical treatments’ solid residue as an adsorbent. In this study continuous fixed-bed-column systems were investigated. Continue-flow experiments were carried out on stainless steel columns with dimensions 15 × 2.5 and 25 × 2.5 cm. In chemical processing, a packed bed is a hollow tube, pipe, or other vessel that is filled with a packing material.
{"title":"Autohydrolyzed Low-Cost Biomass and Adsorbent Aging","authors":"O. Kopsidas","doi":"10.2139/ssrn.3500887","DOIUrl":"https://doi.org/10.2139/ssrn.3500887","url":null,"abstract":"Autohydrolysis or self-hydrolysis or hydrothermal treatment of lignocellulosic materials like sawdust and straw is already used in bioethanol industry for water soluble fermentable sugars production. The main idea in this paper is the use of the autohydrolysis and other thermochemical treatments’ solid residue as an adsorbent. In this study continuous fixed-bed-column systems were investigated. Continue-flow experiments were carried out on stainless steel columns with dimensions 15 × 2.5 and 25 × 2.5 cm. In chemical processing, a packed bed is a hollow tube, pipe, or other vessel that is filled with a packing material.","PeriodicalId":119194,"journal":{"name":"MatSciRN: Other Structural Materials (Topic)","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130600060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Normally tough structural materials may fail catastrophically when contaminated with even minuscule quantities of ubiquitous elements such as sulfur, phosphorus or hydrogen. These so called embrittling elements exert their influence at the tip of atomically sharp cracks where applied stress is concentrated to a degree given by the stress concentration factor. When the concentrated stress exceeds the strength of the bonds across the crack tip, the crack will run. Hence, an element may embrittle a host either by decreasing bond strength and/or increasing the stress concentration. While the effects of embrittling elements on the earlier have been extensively studied, less attention has been directed to their effects on the latter. Here we exploit the nearsightedness of electronic matter principle to provide a measure of the stress concentration factor and study its changes in the presence of a known embrittling element. We find that for the well studied system of copper embrittled by dilute quantities of bismuth, bismuth atoms increase the crack tip stress concentration by more than 60%
{"title":"Embrittlement: A Crack Tip View","authors":"M. Rajivmoorthy, T. Wilson, M. Eberhart","doi":"10.2139/ssrn.3757768","DOIUrl":"https://doi.org/10.2139/ssrn.3757768","url":null,"abstract":"Normally tough structural materials may fail catastrophically when contaminated with even minuscule quantities of ubiquitous elements such as sulfur, phosphorus or hydrogen. These so called embrittling elements exert their influence at the tip of atomically sharp cracks where applied stress is concentrated to a degree given by the stress concentration factor. When the concentrated stress exceeds the strength of the bonds across the crack tip, the crack will run. Hence, an element may embrittle a host either by decreasing bond strength and/or increasing the stress concentration. While the effects of embrittling elements on the earlier have been extensively studied, less attention has been directed to their effects on the latter. Here we exploit the nearsightedness of electronic matter principle to provide a measure of the stress concentration factor and study its changes in the presence of a known embrittling element. We find that for the well studied system of copper embrittled by dilute quantities of bismuth, bismuth atoms increase the crack tip stress concentration by more than 60%","PeriodicalId":119194,"journal":{"name":"MatSciRN: Other Structural Materials (Topic)","volume":"23 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115019273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Previous researches utilizing MER proto-oncogene tyrosine kinase (MERTK) gene therapy in Royal College of Surgeons (RCS) rats evidenced its effectiveness in treating MERTK-associated retinitis pigmentosa (RP). Specific ligands for receptor tyrosine kinases, such as growth arrest-specific 6 (Gas6), may enhance retinal phagocytosis via the MERTK receptor, and consequently, enhance the therapeutic effects of gene therapy. In order to overcome the short life effect of the injected Gas6 protein, we constructed a Gas6 loaded methoxy-poly(ethylene glyeol)-poly(lactic-co-glycolic acid) (mPEG-PLGA) nanoparticles (Gas6 NPs) system which allowed for localized and sustained Gas6 protein release, and therefore, a prolonged biological effect. Our data demonstrated that Gas6 protein release from Gas6 NPs preserved the bioactivity and promoted retinal pigment epithelium (RPE) phagocytosis in vitro. Furthermore, the co-transplantation of AAV2-BEST1-hMERTK and Gas6 NPs protected photoreceptors from degeneration in RCS rats. Electroretinogram responses in the hMERTK, hMERTK/Gas6, and hMERTK/Gas6 NPs groups were significantly higher than that of the control, with the hMERTK/Gas6 NPs group exhibiting the highest response. These findings strongly suggest that Gas6 NPs are a promising method to enable the sustained release of Gas6 protein within the therapeutic window and could therefore enhance the therapeutic effects of gene therapy for MERTK-associated RP.
{"title":"Sustained Release of Gas6 Through MPEG-PLGA Nanoparticles for Enhancing Therapeutic Effects of Gene Therapy for MERTK-Associated Retinitis Pigmentosa","authors":"Shen Wu, Yingyan Mao, Qian Liu, Xuejing Yan, Ningli Wang, Jingxue Zhang","doi":"10.2139/ssrn.3751551","DOIUrl":"https://doi.org/10.2139/ssrn.3751551","url":null,"abstract":"Previous researches utilizing MER proto-oncogene tyrosine kinase (MERTK) gene therapy in Royal College of Surgeons (RCS) rats evidenced its effectiveness in treating MERTK-associated retinitis pigmentosa (RP). Specific ligands for receptor tyrosine kinases, such as growth arrest-specific 6 (Gas6), may enhance retinal phagocytosis via the MERTK receptor, and consequently, enhance the therapeutic effects of gene therapy. In order to overcome the short life effect of the injected Gas6 protein, we constructed a Gas6 loaded methoxy-poly(ethylene glyeol)-poly(lactic-co-glycolic acid) (mPEG-PLGA) nanoparticles (Gas6 NPs) system which allowed for localized and sustained Gas6 protein release, and therefore, a prolonged biological effect. Our data demonstrated that Gas6 protein release from Gas6 NPs preserved the bioactivity and promoted retinal pigment epithelium (RPE) phagocytosis in vitro. Furthermore, the co-transplantation of AAV2-BEST1-hMERTK and Gas6 NPs protected photoreceptors from degeneration in RCS rats. Electroretinogram responses in the hMERTK, hMERTK/Gas6, and hMERTK/Gas6 NPs groups were significantly higher than that of the control, with the hMERTK/Gas6 NPs group exhibiting the highest response. These findings strongly suggest that Gas6 NPs are a promising method to enable the sustained release of Gas6 protein within the therapeutic window and could therefore enhance the therapeutic effects of gene therapy for MERTK-associated RP.","PeriodicalId":119194,"journal":{"name":"MatSciRN: Other Structural Materials (Topic)","volume":"2 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115189608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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