Sang Jin Lee, Youngmin Kim, Tae Wu Kim, Cheolhee Yang, Kamatchi Thamilselvan, Hyeongseop Jeong, J. Hyun, H. Ihee
Molecular switches alterable between two stable states by environmental stimuli such as light and temperature offer the potential for controlling biological functions. Here, we report a photoswitchable protein complex made of multiple protein molecules that can rapidly and reversibly switch with significant conformational changes. The structural and photochromic properties of photoactive yellow protein (PYP) are harnessed to construct circular oligomer PYPs (coPYPs) of desired sizes. Considering the light-induced N-terminal protrusion of monomer PYP, we expected coPYPs would expand upon irradiation, but time-resolved x-ray scattering data reveal that the late intermediate has a light-induced contraction motion. This work not only provides an approach to engineering a novel protein-based molecular switch based on circular oligomers of a well-known protein unit but also demonstrates the importance of actually characterizing the structural dynamics of designed molecular switches.
{"title":"Reversible Molecular Motional Switch Based on Circular Photoactive Protein Oligomers: Unexpected Photo-Induced Contraction","authors":"Sang Jin Lee, Youngmin Kim, Tae Wu Kim, Cheolhee Yang, Kamatchi Thamilselvan, Hyeongseop Jeong, J. Hyun, H. Ihee","doi":"10.2139/ssrn.3858909","DOIUrl":"https://doi.org/10.2139/ssrn.3858909","url":null,"abstract":"Molecular switches alterable between two stable states by environmental stimuli such as light and temperature offer the potential for controlling biological functions. Here, we report a photoswitchable protein complex made of multiple protein molecules that can rapidly and reversibly switch with significant conformational changes. The structural and photochromic properties of photoactive yellow protein (PYP) are harnessed to construct circular oligomer PYPs (coPYPs) of desired sizes. Considering the light-induced N-terminal protrusion of monomer PYP, we expected coPYPs would expand upon irradiation, but time-resolved x-ray scattering data reveal that the late intermediate has a light-induced contraction motion. This work not only provides an approach to engineering a novel protein-based molecular switch based on circular oligomers of a well-known protein unit but also demonstrates the importance of actually characterizing the structural dynamics of designed molecular switches.","PeriodicalId":11894,"journal":{"name":"EngRN: Biomaterials (Topic)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74121635","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}
J. Nulty, Fiona E. Freeman, David C. Browe, Ross Burdis, D. Ahern, Pierluca Pitacco, Yu Bin Lee, E. Alsberg, D. Kelly
For 3D bioprinted tissues to be scaled-up to clinically relevant sizes, effective prevascularisation strategies are required to provide the necessary nutrients for normal metabolism and to remove associated waste by-products. The aim of this study was to develop a bioprinting strategy to engineer prevascularised tissues in vitro and to investigate the capacity of such constructs to enhance the vascularisation and regeneration of large bone defects in vivo. From a screen of different bioinks, a fibrin-based hydrogel was found to best support human umbilical vein endothelial cell (HUVEC) sprouting and the establishment of a microvessel network. When this bioink was combined with HUVECs and supporting human bone marrow stem/stromal cells (hBMSCs), these microvessel networks persisted in vitro. Furthermore, only bioprinted tissues containing both HUVECs and hBMSCs, that were first allowed to mature in vitro, supported robust blood vessel development in vivo. To assess the therapeutic utility of this bioprinting strategy, these bioinks were used to prevascularise 3D printed polycaprolactone (PCL) scaffolds, which were subsequently implanted into critically-sized femoral bone defects in rats. Microcomputed tomography (µCT) angiography revealed increased levels of vascularisation in vivo, which correlated with higher levels of new bone formation. Such prevascularised constructs could be used to enhance the vascularisation of a range of large tissue defects, forming the basis of multiple new bioprinted therapeutics. STATEMENT OF SIGNIFICANCE: This paper demonstrates a versatile 3D bioprinting technique to improve the vascularisation of tissue engineered constructs and further demonstrates how this method can be incorporated into a bone tissue engineering strategy to improve vascularisation in a rat femoral defect model.
{"title":"3D Bioprinting of Prevascularised Implants for the Repair of Critically Sized Bone Defects","authors":"J. Nulty, Fiona E. Freeman, David C. Browe, Ross Burdis, D. Ahern, Pierluca Pitacco, Yu Bin Lee, E. Alsberg, D. Kelly","doi":"10.2139/ssrn.3708678","DOIUrl":"https://doi.org/10.2139/ssrn.3708678","url":null,"abstract":"For 3D bioprinted tissues to be scaled-up to clinically relevant sizes, effective prevascularisation strategies are required to provide the necessary nutrients for normal metabolism and to remove associated waste by-products. The aim of this study was to develop a bioprinting strategy to engineer prevascularised tissues in vitro and to investigate the capacity of such constructs to enhance the vascularisation and regeneration of large bone defects in vivo. From a screen of different bioinks, a fibrin-based hydrogel was found to best support human umbilical vein endothelial cell (HUVEC) sprouting and the establishment of a microvessel network. When this bioink was combined with HUVECs and supporting human bone marrow stem/stromal cells (hBMSCs), these microvessel networks persisted in vitro. Furthermore, only bioprinted tissues containing both HUVECs and hBMSCs, that were first allowed to mature in vitro, supported robust blood vessel development in vivo. To assess the therapeutic utility of this bioprinting strategy, these bioinks were used to prevascularise 3D printed polycaprolactone (PCL) scaffolds, which were subsequently implanted into critically-sized femoral bone defects in rats. Microcomputed tomography (µCT) angiography revealed increased levels of vascularisation in vivo, which correlated with higher levels of new bone formation. Such prevascularised constructs could be used to enhance the vascularisation of a range of large tissue defects, forming the basis of multiple new bioprinted therapeutics. STATEMENT OF SIGNIFICANCE: This paper demonstrates a versatile 3D bioprinting technique to improve the vascularisation of tissue engineered constructs and further demonstrates how this method can be incorporated into a bone tissue engineering strategy to improve vascularisation in a rat femoral defect model.","PeriodicalId":11894,"journal":{"name":"EngRN: Biomaterials (Topic)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80355800","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}
K. Cheng, Xiaosheng Tao, Jiaxin Cao, Zuqiang Yin, S. Kundu, Shenzhou Lu
Super absorbent polymers have a wide range of applications in the fields of biomaterials, agriculture, physiological products of daily-uses, and others. Silk fibroin, as a natural biomaterial with excellent biocompatibility, is showing a good prospect of applications in the field of biomedicine. In this work, silk protein fibroin is used as the carrier, riboflavin as the photosensitizer, and accordingly hydrogel is prepared by free radical cross-linking under ultraviolet light. The fibroin in the hydrogel contains mainly the random coil structure, and the covalent bond cross-linking hinders the crystallization of the silk fibroin, thereby an amorphous silk fibroin hydrogel is obtained. This hydrogel has a capacity to absorb water 90 times more than its own mass, a fast water absorption speed, and absorbs a good amount of water within a minute. This fabricated silk protein fibroin hydrogel having a quick water-absorbing ability; therefore, this can be used for rapid hemostasis of wounds and for absorbing other body exudates.
{"title":"Super Absorbent Silk Fibroin Hydrogel","authors":"K. Cheng, Xiaosheng Tao, Jiaxin Cao, Zuqiang Yin, S. Kundu, Shenzhou Lu","doi":"10.2139/ssrn.3784440","DOIUrl":"https://doi.org/10.2139/ssrn.3784440","url":null,"abstract":"Super absorbent polymers have a wide range of applications in the fields of biomaterials, agriculture, physiological products of daily-uses, and others. Silk fibroin, as a natural biomaterial with excellent biocompatibility, is showing a good prospect of applications in the field of biomedicine. In this work, silk protein fibroin is used as the carrier, riboflavin as the photosensitizer, and accordingly hydrogel is prepared by free radical cross-linking under ultraviolet light. The fibroin in the hydrogel contains mainly the random coil structure, and the covalent bond cross-linking hinders the crystallization of the silk fibroin, thereby an amorphous silk fibroin hydrogel is obtained. This hydrogel has a capacity to absorb water 90 times more than its own mass, a fast water absorption speed, and absorbs a good amount of water within a minute. This fabricated silk protein fibroin hydrogel having a quick water-absorbing ability; therefore, this can be used for rapid hemostasis of wounds and for absorbing other body exudates.","PeriodicalId":11894,"journal":{"name":"EngRN: Biomaterials (Topic)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83741693","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}
Wenjuan Huang, Sijie Zhou, B. Tang, Hongyan Xu, Xiaoxiao Wu, Na Li, Xingjie Zan, W. Geng
Proteins play key roles in most biological processes, and protein dysfunction can cause various diseases. Over the past few decades, tremendous development has occurred in the protein therapeutic market due to the high specificity, low side effects, and low risk of proteins. Currently, all protein drugs on the market are based on extracellular targeting; more than 70% of intracellular targets remain un-druggable. Efficient delivery of cytosolic proteins is of significance for protein drugs, advanced biotechnology and molecular cell biology. Herein, we developed a co-assembly strategy for protein-hexahistidine-metal for intracellular protein delivery. Based on the coordinative interaction between His6 and metal ions, various proteins were encapsulated in situ into nanosized and positively charged protein encapsulation particles(Protein@HmA) through a co-assembly process with a high loading capacity and loading efficiency. Protein@HmA was able to deliver proteins with diverse physicochemical properties through multiple endocytosis pathways, and the protein could quickly escape from endosomes. In addition, the bioactivity of the loaded protein during co-assembly and the intracellular delivery processes were well preserved and could be properly exerted inside cells. Our results demonstrate that this strategy should be a valuable platform for protein delivery and has huge potential in protein-based theranostics. STATEMENT OF SIGNIFICANCE: : Intracellular targets with protein drugs may provide a new way for the treatment of many refractory disease. Herein, we developed a co-assembly strategy for protein-hexahistidine-metal for efficient intracellular protein delivery. Based on the coordinative interaction between His6 and metal ions, various proteins were encapsulated in situ into nanosized and positively charged particles (Protein@HmA) with a high loading efficiency. Protein@HmA was able to deliver different proteins through multiple endocytosis pathways, and the protein could quickly escape from endosomes. In addition, the bioactivity of the loaded protein during co-assembly and the intracellular delivery processes were well preserved and could be properly exerted inside cells. This strategy should be a valuable platform for protein delivery and has huge potential in protein-based theranostics.
{"title":"Efficient Delivery of Cytosolic Proteins by Protein-Hexahistidine-Metal Co-Assemblies","authors":"Wenjuan Huang, Sijie Zhou, B. Tang, Hongyan Xu, Xiaoxiao Wu, Na Li, Xingjie Zan, W. Geng","doi":"10.2139/ssrn.3762206","DOIUrl":"https://doi.org/10.2139/ssrn.3762206","url":null,"abstract":"Proteins play key roles in most biological processes, and protein dysfunction can cause various diseases. Over the past few decades, tremendous development has occurred in the protein therapeutic market due to the high specificity, low side effects, and low risk of proteins. Currently, all protein drugs on the market are based on extracellular targeting; more than 70% of intracellular targets remain un-druggable. Efficient delivery of cytosolic proteins is of significance for protein drugs, advanced biotechnology and molecular cell biology. Herein, we developed a co-assembly strategy for protein-hexahistidine-metal for intracellular protein delivery. Based on the coordinative interaction between His6 and metal ions, various proteins were encapsulated in situ into nanosized and positively charged protein encapsulation particles(Protein@HmA) through a co-assembly process with a high loading capacity and loading efficiency. Protein@HmA was able to deliver proteins with diverse physicochemical properties through multiple endocytosis pathways, and the protein could quickly escape from endosomes. In addition, the bioactivity of the loaded protein during co-assembly and the intracellular delivery processes were well preserved and could be properly exerted inside cells. Our results demonstrate that this strategy should be a valuable platform for protein delivery and has huge potential in protein-based theranostics. STATEMENT OF SIGNIFICANCE: : Intracellular targets with protein drugs may provide a new way for the treatment of many refractory disease. Herein, we developed a co-assembly strategy for protein-hexahistidine-metal for efficient intracellular protein delivery. Based on the coordinative interaction between His6 and metal ions, various proteins were encapsulated in situ into nanosized and positively charged particles (Protein@HmA) with a high loading efficiency. Protein@HmA was able to deliver different proteins through multiple endocytosis pathways, and the protein could quickly escape from endosomes. In addition, the bioactivity of the loaded protein during co-assembly and the intracellular delivery processes were well preserved and could be properly exerted inside cells. This strategy should be a valuable platform for protein delivery and has huge potential in protein-based theranostics.","PeriodicalId":11894,"journal":{"name":"EngRN: Biomaterials (Topic)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87186667","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}
Qiang Liu, Jiangwei Tian, Ye Tian, Qinchao Sun, Dan Sun, Feifei Wang, Haijun Xu, G. Ying, Wang Jigang, A. Yetisen, Nan Jiang
Organic fluorophores/photosensitizers have been widely used in biological imaging and photodynamic and photothermal combination therapy in the first near-infrared windows. However, their applications in the second near-infrared (NIR-II) windows are still limited primarily owing to low fluorescence quantum yields (QYs). Here, a boron dipyrromethene (BDP) as the molecularly engineered thiophene donor unit with high QYs to the redshift is created. Thiophene insertion initiates substantial redshifts of the absorbance, as compared to its counterparts that introduce iodine. The fluorescent molecule can be triggered by a NIR laser with a single wavelength, producing emission in the NIR-II windows. Single NIR laser triggered phototherapeutic nanoparticles (NPs) are developed by encapsulating the BDP and chemotherapy drug docetaxel (DTX) using a synthetical amphiphilic poly(styrene- co -chloromethyl styrene)-graft-poly(ethylene glycol) functionalized with folic acid (FA). These BDP-T-N-DTX-FA NPs not only show superior solubility and high singlet oxygen quantum yield (ΦΔ =62%), but also demonstrate a single NIR laser-triggered multifunctional characteristics. After intravenous injection of the NPs into 4T1 tumor-bearing mice, the accumulation of the NPs in the tumor presented a high signal-to-background ratio (11.8). Furthermore, the 4T1 tumors in mice were almost eradicated by released DTX and PDT/PTT combination therapy from the BDP-T-N-DTX-FA NPs under the single NIR laser excitation.
有机荧光团/光敏剂已广泛应用于生物成像和光动力光热联合治疗的第一个近红外窗口。然而，它们在第二近红外(NIR-II)窗口中的应用仍然受到限制，主要是由于低荧光量子产率(QYs)。在这里，一个硼二吡咯甲烷(BDP)作为分子工程噻吩供体单位具有高的红移QYs。与引入碘相比，噻吩的插入引发了吸光度的实质性红移。荧光分子可以由具有单一波长的近红外激光器触发，在NIR- ii窗口中产生发射。采用叶酸(FA)功能化的两亲性聚(苯乙烯- co -氯甲基苯乙烯)接枝聚乙二醇包封BDP和化疗药物多西他赛(DTX)，制备了单次近红外激光触发光疗纳米颗粒(NPs)。这些BDP-T-N-DTX-FA NPs不仅具有优异的溶解度和高单线态氧量子产率(ΦΔ =62%)，而且具有单次近红外激光触发的多功能特性。向4T1荷瘤小鼠静脉注射NPs后，NPs在肿瘤中的积累呈现高信本比(11.8)。此外，在单次近红外激光激发下，BDP-T-N-DTX-FA NPs释放DTX和PDT/PTT联合治疗小鼠4T1肿瘤几乎被根除。
{"title":"Thiophene Donor for NIR-II Fluorescence Imaging Guided Photothermal/Photodynamic/Chemo Combination Therapy","authors":"Qiang Liu, Jiangwei Tian, Ye Tian, Qinchao Sun, Dan Sun, Feifei Wang, Haijun Xu, G. Ying, Wang Jigang, A. Yetisen, Nan Jiang","doi":"10.2139/ssrn.3762211","DOIUrl":"https://doi.org/10.2139/ssrn.3762211","url":null,"abstract":"Organic fluorophores/photosensitizers have been widely used in biological imaging and photodynamic and photothermal combination therapy in the first near-infrared windows. However, their applications in the second near-infrared (NIR-II) windows are still limited primarily owing to low fluorescence quantum yields (QYs). Here, a boron dipyrromethene (BDP) as the molecularly engineered thiophene donor unit with high QYs to the redshift is created. Thiophene insertion initiates substantial redshifts of the absorbance, as compared to its counterparts that introduce iodine. The fluorescent molecule can be triggered by a NIR laser with a single wavelength, producing emission in the NIR-II windows. Single NIR laser triggered phototherapeutic nanoparticles (NPs) are developed by encapsulating the BDP and chemotherapy drug docetaxel (DTX) using a synthetical amphiphilic poly(styrene- co -chloromethyl styrene)-graft-poly(ethylene glycol) functionalized with folic acid (FA). These BDP-T-N-DTX-FA NPs not only show superior solubility and high singlet oxygen quantum yield (ΦΔ =62%), but also demonstrate a single NIR laser-triggered multifunctional characteristics. After intravenous injection of the NPs into 4T1 tumor-bearing mice, the accumulation of the NPs in the tumor presented a high signal-to-background ratio (11.8). Furthermore, the 4T1 tumors in mice were almost eradicated by released DTX and PDT/PTT combination therapy from the BDP-T-N-DTX-FA NPs under the single NIR laser excitation.","PeriodicalId":11894,"journal":{"name":"EngRN: Biomaterials (Topic)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78066364","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}
L. Boulais, R. Jellali, U. Pereira, E. Leclerc, S. Bencherif, C. Legallais
Microfluidic systems and polymer hydrogels have been widely developed for tissue engineering. Yet, only a few tools combining both approaches, especially for in vitro liver models, are being explored. In this study, an alginate-based cryogel-integrated biochip was engineered for dynamic hepatoma cell line culture in three dimensions (3D). The alginate cryogel was covalently cross-linked in the biochip at subzero temperatures (T < 0 °C) to create a scaffold with high mechanical stability and an interconnected macroporous network. By varying the alginate concentration and the cross-linker ratio, Young's modulus of the cryogel can be fine-tuned between 1.5 and 29 kPa, corresponding to the range of stiffness of the different physiological states of the liver. We demonstrated that HepG2/C3A cells can be cultured and maintained as viable under dynamic conditions in this device up to 6 days. Albumin synthesis and glucose consumption increased over the cell culture days. Moreover, a 3D cell structure was observed across the entire height of the biochip, which was preserved following alginate lyase treatment to remove the cryogel-based scaffold. In summary, these results represent a proof of concept of an interesting cell culture technology that should be further investigated to engineer healthy and cirrhotic liver models.
{"title":"Cryogel-Integrated Biochip for Liver Tissue Engineering","authors":"L. Boulais, R. Jellali, U. Pereira, E. Leclerc, S. Bencherif, C. Legallais","doi":"10.2139/ssrn.3757905","DOIUrl":"https://doi.org/10.2139/ssrn.3757905","url":null,"abstract":"Microfluidic systems and polymer hydrogels have been widely developed for tissue engineering. Yet, only a few tools combining both approaches, especially for in vitro liver models, are being explored. In this study, an alginate-based cryogel-integrated biochip was engineered for dynamic hepatoma cell line culture in three dimensions (3D). The alginate cryogel was covalently cross-linked in the biochip at subzero temperatures (T < 0 °C) to create a scaffold with high mechanical stability and an interconnected macroporous network. By varying the alginate concentration and the cross-linker ratio, Young's modulus of the cryogel can be fine-tuned between 1.5 and 29 kPa, corresponding to the range of stiffness of the different physiological states of the liver. We demonstrated that HepG2/C3A cells can be cultured and maintained as viable under dynamic conditions in this device up to 6 days. Albumin synthesis and glucose consumption increased over the cell culture days. Moreover, a 3D cell structure was observed across the entire height of the biochip, which was preserved following alginate lyase treatment to remove the cryogel-based scaffold. In summary, these results represent a proof of concept of an interesting cell culture technology that should be further investigated to engineer healthy and cirrhotic liver models.","PeriodicalId":11894,"journal":{"name":"EngRN: Biomaterials (Topic)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79738502","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}
A prototype of a relatively cheap laser-based weeding device was developed and tested on couch grass (Elytrigia repens (L.) Desv. ex Nevski) mixed with tomatoes. Three types of laser were used (0.3 W, 1 W, and 5 W). A neural network was trained to identify the weed plants, and a laser guidance system estimated the coordinates of the weed. An algorithm was developed to estimate the energy necessary to harm the weed plants. We also developed a decision model for the weed control device. The energy required to damage a plant depended on the diameter of the plant which was related to plant length. The 1 W laser was not sufficient to eliminate all weed plants and required too long exposure time. The 5 W laser was more efficient but also harmed the crop if the laser beam became split into two during the weeding process. There were several challenges with the device, which needs to be improved upon. In particular, the time of exposure needs to be reduced significantly. Still, the research showed that it is possible to develop a concept for laser weeding using relatively cheap equipment, which can work in complicated situations where weeds and crop are mixed.
{"title":"A Concept of a Compact and Inexpensive Device for Controlling Weeds with Laser Beams","authors":"I. Rakhmatulin, C. Andreasen","doi":"10.2139/ssrn.3716607","DOIUrl":"https://doi.org/10.2139/ssrn.3716607","url":null,"abstract":"A prototype of a relatively cheap laser-based weeding device was developed and tested on couch grass (Elytrigia repens (L.) Desv. ex Nevski) mixed with tomatoes. Three types of laser were used (0.3 W, 1 W, and 5 W). A neural network was trained to identify the weed plants, and a laser guidance system estimated the coordinates of the weed. An algorithm was developed to estimate the energy necessary to harm the weed plants. We also developed a decision model for the weed control device. The energy required to damage a plant depended on the diameter of the plant which was related to plant length. The 1 W laser was not sufficient to eliminate all weed plants and required too long exposure time. The 5 W laser was more efficient but also harmed the crop if the laser beam became split into two during the weeding process. There were several challenges with the device, which needs to be improved upon. In particular, the time of exposure needs to be reduced significantly. Still, the research showed that it is possible to develop a concept for laser weeding using relatively cheap equipment, which can work in complicated situations where weeds and crop are mixed.","PeriodicalId":11894,"journal":{"name":"EngRN: Biomaterials (Topic)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90286478","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}
Nurul Dinah Kadir, Zheng Yang, Afizah Hassan, Vinitha Denslin, E. Lee
Secretome profiles of mesenchymal stem cells (MSCs) are reflective of their local microenvironments and exert an impact on the surrounding cells, eliciting regenerative responses that creates an opportunity for exploiting MSCs towards a cell-free therapy for cartilage repair. The conventional method of culturing MSCs on a tissue culture plate does not provide the physiological microenvironment for optimum secretome production. This study explored the potential of fibrous scaffolds with specific surface topographies in influencing the MSC secretome production and in enhancing the functionality of MSCs and chondrocytes for cartilage repair. Conditioned media generated from MSCs cultured on fibrous scaffolds improved secretome yield and profile that promoted migration, proliferation, chondrogenesis, as well as mitigated inflammation and protected chondrocytes from apoptosis. FAK and ERK signaling were identified as the mechanotransduction pathways to modulate the MSC morphology and its secretome production, which highlighted scaffold fiber orientation as a key design parameter to direct cellular behavior of MSCs and enhance its paracrine functions. This study demonstrates that a fibrous culture platform could be a more efficient approach for improving and fine-tuning the repertoire of MSC secretome for articular cartilage regeneration.
{"title":"Fibrous Scaffolds Enhanced the Paracrine Signaling of Mesenchymal Stem Cells for Cartilage Regeneration","authors":"Nurul Dinah Kadir, Zheng Yang, Afizah Hassan, Vinitha Denslin, E. Lee","doi":"10.2139/ssrn.3687964","DOIUrl":"https://doi.org/10.2139/ssrn.3687964","url":null,"abstract":"Secretome profiles of mesenchymal stem cells (MSCs) are reflective of their local microenvironments and exert an impact on the surrounding cells, eliciting regenerative responses that creates an opportunity for exploiting MSCs towards a cell-free therapy for cartilage repair. The conventional method of culturing MSCs on a tissue culture plate does not provide the physiological microenvironment for optimum secretome production. This study explored the potential of fibrous scaffolds with specific surface topographies in influencing the MSC secretome production and in enhancing the functionality of MSCs and chondrocytes for cartilage repair. Conditioned media generated from MSCs cultured on fibrous scaffolds improved secretome yield and profile that promoted migration, proliferation, chondrogenesis, as well as mitigated inflammation and protected chondrocytes from apoptosis. FAK and ERK signaling were identified as the mechanotransduction pathways to modulate the MSC morphology and its secretome production, which highlighted scaffold fiber orientation as a key design parameter to direct cellular behavior of MSCs and enhance its paracrine functions. This study demonstrates that a fibrous culture platform could be a more efficient approach for improving and fine-tuning the repertoire of MSC secretome for articular cartilage regeneration.","PeriodicalId":11894,"journal":{"name":"EngRN: Biomaterials (Topic)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78452906","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}
Glaucoma is the global leading cause of irreversible blindness. It is a chronic progressive disorder and, therefore, often requires long-term management with drugs on patients' discretion. However, there is a shortage of antiglaucoma drugs in the current market due to their low bioavailability. This is because there are multiple biological barriers of the human eyes, thereby leading to increased demands for frequent dosage regimen per day of these drugs, which could result in concomitant side effects and eventually reduced patient compliance. Recently, nanomedicines have become optimized alternatives to conventional ophthalmic formulations due to advantages of improved barrier permeability, sustained drug release, tissue targeting, and lowered systemic absorption of instilled medications. These merits provide the active ingredients in these nanomedicines an effective manner to reach the ideal concentrations at sites of damaged nerves, offering a promising platform for neuroprotective treatment of these conditions. In this study, nanomedicines and nanomedicine-based novel strategies for pharmacotherapy of glaucoma were reviewed, including liposomes, niosomes, nanoparticles, and dendrimers. This article intends to offer a comprehensive review of frontier progresses as well as hotspots and issues that appeared in the field of nanomedicines, which may enable a practical flourish in the future.
{"title":"Nanomedicines for the Treatment of Glaucoma: Current Status and Future Perspectives","authors":"Zimeng Zhai, Yiyun Cheng, Jiaxu Hong","doi":"10.2139/ssrn.3683604","DOIUrl":"https://doi.org/10.2139/ssrn.3683604","url":null,"abstract":"Glaucoma is the global leading cause of irreversible blindness. It is a chronic progressive disorder and, therefore, often requires long-term management with drugs on patients' discretion. However, there is a shortage of antiglaucoma drugs in the current market due to their low bioavailability. This is because there are multiple biological barriers of the human eyes, thereby leading to increased demands for frequent dosage regimen per day of these drugs, which could result in concomitant side effects and eventually reduced patient compliance. Recently, nanomedicines have become optimized alternatives to conventional ophthalmic formulations due to advantages of improved barrier permeability, sustained drug release, tissue targeting, and lowered systemic absorption of instilled medications. These merits provide the active ingredients in these nanomedicines an effective manner to reach the ideal concentrations at sites of damaged nerves, offering a promising platform for neuroprotective treatment of these conditions. In this study, nanomedicines and nanomedicine-based novel strategies for pharmacotherapy of glaucoma were reviewed, including liposomes, niosomes, nanoparticles, and dendrimers. This article intends to offer a comprehensive review of frontier progresses as well as hotspots and issues that appeared in the field of nanomedicines, which may enable a practical flourish in the future.","PeriodicalId":11894,"journal":{"name":"EngRN: Biomaterials (Topic)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77650892","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}
M. Jadidi, S. A. Razian, Mahmoud Habibnezhad, Eric Anttila, A. Kamenskiy
Elastic and muscular arteries differ in structure, function, and mechanical properties, and may adapt differently to aging. We compared the descending thoracic aortas (TA) and the superficial femoral arteries (SFA) of 27 tissue donors (average 41±18 years, range 13-73 years) using planar biaxial testing, constitutive modeling, and bidirectional histology. Both TAs and SFAs increased in size with age, with the outer radius increasing more than the inner radius, but the TAs thickened 6-fold and widened 3-fold faster than the SFAs. The circumferential opening angle did not change in the TA, but increased 2.4-fold in the SFA. Young TAs were relatively isotropic, but the anisotropy increased with age due to longitudinal stiffening. SFAs were 51% more compliant longitudinally irrespective of age. Older TAs and SFAs were stiffer, but the SFA stiffened 5.6-fold faster circumferentially than the TA. Physiologic stresses decreased with age in both arteries, with greater changes occurring longitudinally. TAs had larger circumferential, but smaller longitudinal stresses than the SFAs, larger cardiac cycle stretch, 36% lower circumferential stiffness, and 8-fold more elastic energy available for pulsation. TAs contained elastin sheets separated by smooth muscle cells (SMCs), collagen, and glycosaminoglycans, while the SFAs had SMCs, collagen, and longitudinal elastic fibers. With age, densities of elastin and SMCs decreased, collagen remained constant due to medial thickening, and the glycosaminoglycans increased. Elastic and muscular arteries demonstrate different morphological, mechanical, physiologic, and structural characteristics and adapt differently to aging. While the aortas remodel to preserve the Windkessel function, the SFAs maintain higher longitudinal compliance.
{"title":"Mechanical, Structural, and Physiologic Differences in Human Elastic and Muscular Arteries of Different Ages: Comparison of the Thoracic Aorta to the Superficial Femoral Artery","authors":"M. Jadidi, S. A. Razian, Mahmoud Habibnezhad, Eric Anttila, A. Kamenskiy","doi":"10.2139/ssrn.3681037","DOIUrl":"https://doi.org/10.2139/ssrn.3681037","url":null,"abstract":"Elastic and muscular arteries differ in structure, function, and mechanical properties, and may adapt differently to aging. We compared the descending thoracic aortas (TA) and the superficial femoral arteries (SFA) of 27 tissue donors (average 41±18 years, range 13-73 years) using planar biaxial testing, constitutive modeling, and bidirectional histology. Both TAs and SFAs increased in size with age, with the outer radius increasing more than the inner radius, but the TAs thickened 6-fold and widened 3-fold faster than the SFAs. The circumferential opening angle did not change in the TA, but increased 2.4-fold in the SFA. Young TAs were relatively isotropic, but the anisotropy increased with age due to longitudinal stiffening. SFAs were 51% more compliant longitudinally irrespective of age. Older TAs and SFAs were stiffer, but the SFA stiffened 5.6-fold faster circumferentially than the TA. Physiologic stresses decreased with age in both arteries, with greater changes occurring longitudinally. TAs had larger circumferential, but smaller longitudinal stresses than the SFAs, larger cardiac cycle stretch, 36% lower circumferential stiffness, and 8-fold more elastic energy available for pulsation. TAs contained elastin sheets separated by smooth muscle cells (SMCs), collagen, and glycosaminoglycans, while the SFAs had SMCs, collagen, and longitudinal elastic fibers. With age, densities of elastin and SMCs decreased, collagen remained constant due to medial thickening, and the glycosaminoglycans increased. Elastic and muscular arteries demonstrate different morphological, mechanical, physiologic, and structural characteristics and adapt differently to aging. While the aortas remodel to preserve the Windkessel function, the SFAs maintain higher longitudinal compliance.","PeriodicalId":11894,"journal":{"name":"EngRN: Biomaterials (Topic)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88567404","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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