The modest clinical impact of musculoskeletal tissue engineering (TE) can be attributed, at least in part, to a failure to recapitulate the structure, composition and functional properties of the target tissue. This has motived increased interest in developmentally inspired TE strategies, which seek to recapitulate key events that occur during embryonic and post-natal development, as a means of generating truly biomimetic grafts to replace or regenerate damaged tissues and organs. Such TE strategies can be substantially enabled by emerging biofabrication and bioprinting strategies, and in particular the use of cellular aggregates and microtissues as ‘building blocks’ for the development of larger tissues and/or organ precursors. Here, the application of cellular aggregates and microtissues for the engineering of musculoskeletal tissues, from vascularised bone to zonally organized articular cartilage, will be reviewed. The importance of first scaling-down to later scale-up will be discussed, as this is viewed as a key component of engineering functional grafts using cellular aggregates or microtissues. In the context of engineering anatomically accurate tissues of scale suitable for tissue engineering and regenerative medicine applications, novel bioprinting modalities and their application in controlling the process by which cellular aggregates or microtissues fuse and self-organise will be reviewed. Throughout the paper we will highlight some of the key challenges facing this emerging field.
{"title":"Biofabrication and Bioprinting Using Cellular Aggregates and Microtissues for the Engineering of Musculoskeletal Tissues","authors":"Ross Burdis, D. Kelly","doi":"10.2139/ssrn.3739622","DOIUrl":"https://doi.org/10.2139/ssrn.3739622","url":null,"abstract":"The modest clinical impact of musculoskeletal tissue engineering (TE) can be attributed, at least in part, to a failure to recapitulate the structure, composition and functional properties of the target tissue. This has motived increased interest in developmentally inspired TE strategies, which seek to recapitulate key events that occur during embryonic and post-natal development, as a means of generating truly biomimetic grafts to replace or regenerate damaged tissues and organs. Such TE strategies can be substantially enabled by emerging biofabrication and bioprinting strategies, and in particular the use of cellular aggregates and microtissues as ‘building blocks’ for the development of larger tissues and/or organ precursors. Here, the application of cellular aggregates and microtissues for the engineering of musculoskeletal tissues, from vascularised bone to zonally organized articular cartilage, will be reviewed. The importance of first scaling-down to later scale-up will be discussed, as this is viewed as a key component of engineering functional grafts using cellular aggregates or microtissues. In the context of engineering anatomically accurate tissues of scale suitable for tissue engineering and regenerative medicine applications, novel bioprinting modalities and their application in controlling the process by which cellular aggregates or microtissues fuse and self-organise will be reviewed. Throughout the paper we will highlight some of the key challenges facing this emerging field.","PeriodicalId":8928,"journal":{"name":"Biomaterials eJournal","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86517597","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}
Parkinson's disease (PD) is a common neurodegenerative disease characterized by a progressive loss of fine motor function that impacts 1-2 out of 1,000 people. PD occurs predominately late in life and lacks a definitive biomarker for early detection. Recent cross-disciplinary progress has implicated the gut as a potential origin of PD pathogenesis. The gut-origin hypothesis has motivated research on gut PD pathology and transmission to the brain, especially during the prodromal stage (10-20 years before motor symptom onset). Early findings have revealed several possible triggers for Lewy pathology - the pathological hallmark of PD - in the gut, suggesting that microbiome and epithelial interactions may play a greater than appreciated role. But the mechanisms driving Lewy pathology and gut-brain transmission in PD remain unknown. Development of artificial α-Synuclein aggregates (α-Syn preformed fibrils) and animal disease models have recapitulated features of PD progression, enabling for the first time, controlled investigation of the gut-origin hypothesis. However, the role of specific cells in PD transmission, such as neurons, remains limited and requires in vitro models for controlled evaluation and perturbation. Human cell populations, three-dimensional organoids, and microfluidics as discovery platforms inch us closer to improving existing treatment for patients by providing platforms for discovery and screening. This review includes a discussion of PD pathology, conventional treatments, in vivo and in vitro models, and future directions. STATEMENT OF SIGNIFICANCE: Parkinson's Disease remains a common neurodegenerative disease with palliative versus causal treatments. Recently, the gut-origin hypothesis, where Parkinson's disease is thought to originate and spread from the gut to the brain, has gained traction as a field of investigation. However, despite the wealth of studies and innovative approaches to accelerate the field, there remains a need for in vitro tools to enable fundamental biological understanding of disease progression, and compound screening and efficacy. In this review, we present a historical perspective of Parkinson's Disease pathogenesis, detection, and conventional therapy, animal and human models investigating the gut-origin hypothesis, in vitro models to enable controlled discovery, and future outlooks for this blossoming field.
{"title":"Parkinson's Disease and the Gut: Models of an Emerging Relationship","authors":"A. Bindas, S. Kulkarni, R. Koppes, A. Koppes","doi":"10.2139/ssrn.3739626","DOIUrl":"https://doi.org/10.2139/ssrn.3739626","url":null,"abstract":"Parkinson's disease (PD) is a common neurodegenerative disease characterized by a progressive loss of fine motor function that impacts 1-2 out of 1,000 people. PD occurs predominately late in life and lacks a definitive biomarker for early detection. Recent cross-disciplinary progress has implicated the gut as a potential origin of PD pathogenesis. The gut-origin hypothesis has motivated research on gut PD pathology and transmission to the brain, especially during the prodromal stage (10-20 years before motor symptom onset). Early findings have revealed several possible triggers for Lewy pathology - the pathological hallmark of PD - in the gut, suggesting that microbiome and epithelial interactions may play a greater than appreciated role. But the mechanisms driving Lewy pathology and gut-brain transmission in PD remain unknown. Development of artificial α-Synuclein aggregates (α-Syn preformed fibrils) and animal disease models have recapitulated features of PD progression, enabling for the first time, controlled investigation of the gut-origin hypothesis. However, the role of specific cells in PD transmission, such as neurons, remains limited and requires in vitro models for controlled evaluation and perturbation. Human cell populations, three-dimensional organoids, and microfluidics as discovery platforms inch us closer to improving existing treatment for patients by providing platforms for discovery and screening. This review includes a discussion of PD pathology, conventional treatments, in vivo and in vitro models, and future directions. STATEMENT OF SIGNIFICANCE: Parkinson's Disease remains a common neurodegenerative disease with palliative versus causal treatments. Recently, the gut-origin hypothesis, where Parkinson's disease is thought to originate and spread from the gut to the brain, has gained traction as a field of investigation. However, despite the wealth of studies and innovative approaches to accelerate the field, there remains a need for in vitro tools to enable fundamental biological understanding of disease progression, and compound screening and efficacy. In this review, we present a historical perspective of Parkinson's Disease pathogenesis, detection, and conventional therapy, animal and human models investigating the gut-origin hypothesis, in vitro models to enable controlled discovery, and future outlooks for this blossoming field.","PeriodicalId":8928,"journal":{"name":"Biomaterials eJournal","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85903006","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}
Abstract Artificial scaffolds fabricated for tissue engineering and/or regenerative medicine applications typically aim to resemble specific properties of the innate extracellular matrix of a particular tissue. While there have been successes with this approach, it has become apparent that there are certain scaffold properties that are essential for tissue formation. Other, non-essential, properties, however, can aid in tissue formation but are not required for cell growth, maintenance and the formation of viable tissue engineered scaffolds. We aimed to investigate the role of electrospun scaffold topography on endothelial cell and platelet functions related to vascular growth throughout engineered scaffolds. We hypothesized that the growth and compatibility of cells throughout scaffolds would be enhanced as the scaffold topographical organization increased. To test this, we made use of a customized rotational electrospinning apparatus, which can increase the topographical organization of formed scaffolds. Scaffolds fabricated from cellulose acetate, chitosan and/or poly-caprolactone were tested. Our data illustrates that endothelial cells prefer to be cultured on scaffolds with increasing order and larger fiber diameters. In general, platelet activation, adhesion and aggregation responses were not a function of scaffold composition, however, platelets activation and adhesion was generally reduced in the presence of scaffolds, as compared to samples incubated without scaffolds. These results indicate that engineered scaffold properties should be fine-tuned for particular applications and overall, scaffolds may not need to resemble the extracellular matrix in all physical, mechanical and topographical properties to be successful in tissue engineering applications. Statement of Significance When designing engineered tissues, one must consider the physical properties of formed scaffolds as a means to control cell growth characteristics throughout the engineered scaffold. To date, there has been little agreement about which scaffold physical properties are essential for tissue growth. Further, it is essential for growing tissue to include patent vascular networks and here we optimized a method to control the organization of fibers within electrospun scaffolds and promote vascular network growth throughout those scaffolds. Importantly, with increasing fiber organization, scaffolds performed better for vascular tissue engineering applications, in terms of endothelial cell and platelet performance.
{"title":"Electrospun Scaffold Fiber Orientation Regulates Endothelial Cell and Platelet Properties Associated with Angiogenesis and Hemocompatibility","authors":"D. Rubenstein, Vaughn K. Greene, W. Yin","doi":"10.2139/ssrn.3693555","DOIUrl":"https://doi.org/10.2139/ssrn.3693555","url":null,"abstract":"Abstract Artificial scaffolds fabricated for tissue engineering and/or regenerative medicine applications typically aim to resemble specific properties of the innate extracellular matrix of a particular tissue. While there have been successes with this approach, it has become apparent that there are certain scaffold properties that are essential for tissue formation. Other, non-essential, properties, however, can aid in tissue formation but are not required for cell growth, maintenance and the formation of viable tissue engineered scaffolds. We aimed to investigate the role of electrospun scaffold topography on endothelial cell and platelet functions related to vascular growth throughout engineered scaffolds. We hypothesized that the growth and compatibility of cells throughout scaffolds would be enhanced as the scaffold topographical organization increased. To test this, we made use of a customized rotational electrospinning apparatus, which can increase the topographical organization of formed scaffolds. Scaffolds fabricated from cellulose acetate, chitosan and/or poly-caprolactone were tested. Our data illustrates that endothelial cells prefer to be cultured on scaffolds with increasing order and larger fiber diameters. In general, platelet activation, adhesion and aggregation responses were not a function of scaffold composition, however, platelets activation and adhesion was generally reduced in the presence of scaffolds, as compared to samples incubated without scaffolds. These results indicate that engineered scaffold properties should be fine-tuned for particular applications and overall, scaffolds may not need to resemble the extracellular matrix in all physical, mechanical and topographical properties to be successful in tissue engineering applications. Statement of Significance When designing engineered tissues, one must consider the physical properties of formed scaffolds as a means to control cell growth characteristics throughout the engineered scaffold. To date, there has been little agreement about which scaffold physical properties are essential for tissue growth. Further, it is essential for growing tissue to include patent vascular networks and here we optimized a method to control the organization of fibers within electrospun scaffolds and promote vascular network growth throughout those scaffolds. Importantly, with increasing fiber organization, scaffolds performed better for vascular tissue engineering applications, in terms of endothelial cell and platelet performance.","PeriodicalId":8928,"journal":{"name":"Biomaterials eJournal","volume":"65 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76327324","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}
In the contemporary educational system, school-based crime laboratories offering BS Criminology program are outdated, no sufficient equipment that are being utilized by the students, however, in the current educational situation, school-based crime laboratories have evolved and progressed due to advancements in knowledge and technology and continued efforts to strengthen standardization and accreditation provided by the CHED Memorandums. Most of the private and public universities and colleges exerted efforts to include: the implementation of new techniques and instruments such as the creation of innovative utility models that are produced by the students and faculty members that provides easier laboratory experiences and experiments; research to better understand the scientific methods and its limitations; and the increased of demand in using modern and technological facilities used in Criminalistics laboratory subjects like the creation of school-based Automated Fingerprint Identification System. The study adopted the descriptive method of research and qualitative research designs to assess the need of digitized laboratory equipment in teaching Personal Identification Techniques. The result of the analysis revealed existing similarities of needs in the development of digitizing most of the laboratory equipment used in the institution should be addressed through the conduct of needs assessment of the stakeholders and the beneficiaries in the education system especially in courses offering specialization. The result of the study implied a clear indication that the development of School-Based Digital Fingerprint Laboratory equipment is highly encouraged that are not limited to Hand and Fingerprint Digital Scanning; Fingerprint database system; 2D or 3D technology court presentations and Digital fingerprint classification formula and extension.
{"title":"School-Based Fingerprint Laboratory Simulator: A Needs Assessment","authors":"J. Benter","doi":"10.2139/ssrn.3734137","DOIUrl":"https://doi.org/10.2139/ssrn.3734137","url":null,"abstract":"In the contemporary educational system, school-based crime laboratories offering BS Criminology program are outdated, no sufficient equipment that are being utilized by the students, however, in the current educational situation, school-based crime laboratories have evolved and progressed due to advancements in knowledge and technology and continued efforts to strengthen standardization and accreditation provided by the CHED Memorandums. Most of the private and public universities and colleges exerted efforts to include: the implementation of new techniques and instruments such as the creation of innovative utility models that are produced by the students and faculty members that provides easier laboratory experiences and experiments; research to better understand the scientific methods and its limitations; and the increased of demand in using modern and technological facilities used in Criminalistics laboratory subjects like the creation of school-based Automated Fingerprint Identification System. \u0000 \u0000The study adopted the descriptive method of research and qualitative research designs to assess the need of digitized laboratory equipment in teaching Personal Identification Techniques. \u0000 \u0000The result of the analysis revealed existing similarities of needs in the development of digitizing most of the laboratory equipment used in the institution should be addressed through the conduct of needs assessment of the stakeholders and the beneficiaries in the education system especially in courses offering specialization. \u0000 \u0000The result of the study implied a clear indication that the development of School-Based Digital Fingerprint Laboratory equipment is highly encouraged that are not limited to Hand and Fingerprint Digital Scanning; Fingerprint database system; 2D or 3D technology court presentations and Digital fingerprint classification formula and extension.","PeriodicalId":8928,"journal":{"name":"Biomaterials eJournal","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73081711","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}
COVID-19 was particularly deadly and widespread in the United States because of political incompetence at both state and federal levels, a non-compliant public that flouted prescribed safety measures, and a distrust of science and expertise. At the heart of all of these issues was the branding of the disease as a partisan problem. In 2019, I published the book "Political Brands," which described the hardening of partisan information silos among the American electorate. I wrote this book before the novel SARS-CoV-2 coronavirus (“COVID-19”) pandemic erupted in the United States. A coronavirus cannot pick a side of a political fight. But the way the American public processed COVID-19 fell into the same information silos described in "Political Brands" that facilitated partisan differences of opinion on the presidency of Donald Trump, the legality of his actions, and the appropriateness of his impeachment. To over-simplify, the disease itself became branded politically, and how the individual responded to the deadly pandemic was determined by which silo they occupied.
{"title":"The Political Branding of COVID-19: A Narrative Explained by President Trump’s Five Stages of Grief","authors":"Ciara Torres-Spelliscy","doi":"10.2139/ssrn.3731154","DOIUrl":"https://doi.org/10.2139/ssrn.3731154","url":null,"abstract":"COVID-19 was particularly deadly and widespread in the United States because of political incompetence at both state and federal levels, a non-compliant public that flouted prescribed safety measures, and a distrust of science and expertise. At the heart of all of these issues was the branding of the disease as a partisan problem. In 2019, I published the book \"Political Brands,\" which described the hardening of partisan information silos among the American electorate. I wrote this book before the novel SARS-CoV-2 coronavirus (“COVID-19”) pandemic erupted in the United States. A coronavirus cannot pick a side of a political fight. But the way the American public processed COVID-19 fell into the same information silos described in \"Political Brands\" that facilitated partisan differences of opinion on the presidency of Donald Trump, the legality of his actions, and the appropriateness of his impeachment. To over-simplify, the disease itself became branded politically, and how the individual responded to the deadly pandemic was determined by which silo they occupied.","PeriodicalId":8928,"journal":{"name":"Biomaterials eJournal","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85919122","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}
Ali-Akbar Karkhaneh Yousefi, C. Petit, V. A. A. Santamaría
Smooth Muscle Cells (SMCs) play a vital role in maintaining homeostasis in the aorta by sensing and responding to mechanical stimuli. However, the mechanisms that underlie the ability of SMCs to sense and respond to stiffness change in their environment are still partially unclear. In this study, we focus on the role of acto-myosin contractility in stiffness sensing and introduce a novel continuum mechanics approach based on the principles of thermal strains. Each stress fiber satisfies a universal stress-strain relationship driven by a Young’s modulus, a contraction coefficient scaling the fictitious thermal strain, a maximum contraction stress and a softening parameter describing slipping effects at the weakest links. To account for the inherent variability of cellular responses, large populations of SMCs are modeled with the finite-element method, each cell having a random number and a random arrangement of stress fibers. Moreover, the level of myosin activation in each stress fiber satisfies a Weibull probability density function. Model predictions are compared to traction force measurements on different SMC lineages. It is demonstrated that the model not only predicts well the effects of substrate stiffness on cellular traction, but it can also successfully approximate the statistical variations of cellular tractions induced by intercellular variability. Finally, stresses in the nuclear envelope and in the nucleus are computed with the model, showing that the variations of cytoskeletal forces induced by substrate stiffness directly induce deformations of the nuclear envelope and of the nucleus, which can potentially alter gene expression. The predictability of the model combined to its relative simplicity are promising assets for further investigation of stiffness sensing in multicellular 3D environments. Eventually, this could contribute to decipher the effects of mechanosensitivity impairment, which are known to be at the root of aortic aneurysms.
{"title":"Stiffness Sensing by Aortic Smooth Muscle Cells: Continuum Mechanics Modeling of the Acto-Myosin Role","authors":"Ali-Akbar Karkhaneh Yousefi, C. Petit, V. A. A. Santamaría","doi":"10.2139/ssrn.3716042","DOIUrl":"https://doi.org/10.2139/ssrn.3716042","url":null,"abstract":"Smooth Muscle Cells (SMCs) play a vital role in maintaining homeostasis in the aorta by sensing and responding to mechanical stimuli. However, the mechanisms that underlie the ability of SMCs to sense and respond to stiffness change in their environment are still partially unclear. In this study, we focus on the role of acto-myosin contractility in stiffness sensing and introduce a novel continuum mechanics approach based on the principles of thermal strains. Each stress fiber satisfies a universal stress-strain relationship driven by a Young’s modulus, a contraction coefficient scaling the fictitious thermal strain, a maximum contraction stress and a softening parameter describing slipping effects at the weakest links. To account for the inherent variability of cellular responses, large populations of SMCs are modeled with the finite-element method, each cell having a random number and a random arrangement of stress fibers. Moreover, the level of myosin activation in each stress fiber satisfies a Weibull probability density function. Model predictions are compared to traction force measurements on different SMC lineages. It is demonstrated that the model not only predicts well the effects of substrate stiffness on cellular traction, but it can also successfully approximate the statistical variations of cellular tractions induced by intercellular variability. Finally, stresses in the nuclear envelope and in the nucleus are computed with the model, showing that the variations of cytoskeletal forces induced by substrate stiffness directly induce deformations of the nuclear envelope and of the nucleus, which can potentially alter gene expression. The predictability of the model combined to its relative simplicity are promising assets for further investigation of stiffness sensing in multicellular 3D environments. Eventually, this could contribute to decipher the effects of mechanosensitivity impairment, which are known to be at the root of aortic aneurysms.","PeriodicalId":8928,"journal":{"name":"Biomaterials eJournal","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85917649","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}
Nooshin Zandi, Banafsheh Dolatyar, Roya Lotfi, Yousef Shallageh, M. Shokrgozar, E. Tamjid, N. Annabi, A. Simchi
Wound healing is a complex process based on the coordinated signaling molecules and dynamic interactions between the engineered scaffold and newly formed tissue. So far, most of the engineered scaffolds used for the healing of full-thickness skin wounds do not mimic the natural extracellular matrix (ECM) complexity and therefore are not able to provide an appropriate niche for endogenous tissue regeneration [1]. To address this gap and to accelerate the wound healing process, we present biomimetic bilayer scaffolds compositing of gelatin nanofibers (GFS) and photocrosslinkable composite hydrogels loaded with epidermal growth factors (EGF). The nanofibers operate as the dermis layer, and EGF-loaded composite hydrogels acted as the epidermis matrix for the full-thickness wound healing application. The hydrogels are composed of gelatin metacryloyl (GelMA) modified with silicate nanoplatelets (Laponite). To overcome the challenges of transdermal delivery of EGF, including short half-life and lack of efficient formulation precise, controlled delivery was attained by immobilization of EGF on Laponite. It is shown that the addition of 1wt% silicate nanoplatelet increases the compressive modulus of the hydrogels by 170%. In vitro wound closure analysis also demonstrated improved adhesion of the scaffolds to the native tissue by 3.5 folds. Moreover, the tunable hemostatic ability of the scaffolds due to the negatively charged nanoplatelets is shown. In an established excisional full-thickness wound model, an enhanced wound closure (up to 93.1 ± 1.5%) after 14 days relative to controls (GFS and saline-treated groups) is demonstrated. The engineered adhesive and hemostatic scaffolds with sustained release of the growth factors have the potential to stimulate complete skin regeneration for full-thickness wound healing.
{"title":"Biomimetic Nanoengineered Scaffold for Enhanced Full-Thickness Cutaneous Wound Healing","authors":"Nooshin Zandi, Banafsheh Dolatyar, Roya Lotfi, Yousef Shallageh, M. Shokrgozar, E. Tamjid, N. Annabi, A. Simchi","doi":"10.2139/ssrn.3687902","DOIUrl":"https://doi.org/10.2139/ssrn.3687902","url":null,"abstract":"Wound healing is a complex process based on the coordinated signaling molecules and dynamic interactions between the engineered scaffold and newly formed tissue. So far, most of the engineered scaffolds used for the healing of full-thickness skin wounds do not mimic the natural extracellular matrix (ECM) complexity and therefore are not able to provide an appropriate niche for endogenous tissue regeneration [1]. To address this gap and to accelerate the wound healing process, we present biomimetic bilayer scaffolds compositing of gelatin nanofibers (GFS) and photocrosslinkable composite hydrogels loaded with epidermal growth factors (EGF). The nanofibers operate as the dermis layer, and EGF-loaded composite hydrogels acted as the epidermis matrix for the full-thickness wound healing application. The hydrogels are composed of gelatin metacryloyl (GelMA) modified with silicate nanoplatelets (Laponite). To overcome the challenges of transdermal delivery of EGF, including short half-life and lack of efficient formulation precise, controlled delivery was attained by immobilization of EGF on Laponite. It is shown that the addition of 1wt% silicate nanoplatelet increases the compressive modulus of the hydrogels by 170%. In vitro wound closure analysis also demonstrated improved adhesion of the scaffolds to the native tissue by 3.5 folds. Moreover, the tunable hemostatic ability of the scaffolds due to the negatively charged nanoplatelets is shown. In an established excisional full-thickness wound model, an enhanced wound closure (up to 93.1 ± 1.5%) after 14 days relative to controls (GFS and saline-treated groups) is demonstrated. The engineered adhesive and hemostatic scaffolds with sustained release of the growth factors have the potential to stimulate complete skin regeneration for full-thickness wound healing.","PeriodicalId":8928,"journal":{"name":"Biomaterials eJournal","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86093355","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}
Elham Sameiyan, Elnaz Bagheri, Shahrzad Dehghani, M. Ramezani, M. Alibolandi, K. Abnous, S. M. Taghdisi
In recent years, many stimuli-triggered drug delivery platforms have been designed to deliver drugs accurately to specific sites and reduce their side effects, improving “on-demand” therapeutic efficacy. Adenosine-5'-triphosphate (ATP)-responsive drug delivery methods are examples of these systems that use ATP molecules as a trigger for delivery of therapeutic agents. Since intra- and extra-cellular ATP concentrations are significantly different from each other (1-10 mM and <0.4 mM, respectively), the use of ATP can be a practical method for regulating drug release. Aptamers possess unique properties including, ligand-specific response, short sequence (~ 20-80 bases) and easy functionalization. Thus, their combination with ATP-responsive systems results in more accurate drug delivery systems and greater control of drug release. A wide range of nanoparticle frameworks, such as polymeric nanogels, liposomes, metallic nanoparticles, protein, or DNA nano-assemblies, have been employed in the fabrication of nanocarriers. In this review, we describe several ATP-responsive drug delivery systems based on the various carriers and discuss the challenges and strengths of each method.
{"title":"Aptamer-Based Atp-Responsive Delivery Systems for Diagnosis and Treatment of Cancer","authors":"Elham Sameiyan, Elnaz Bagheri, Shahrzad Dehghani, M. Ramezani, M. Alibolandi, K. Abnous, S. M. Taghdisi","doi":"10.2139/ssrn.3687916","DOIUrl":"https://doi.org/10.2139/ssrn.3687916","url":null,"abstract":"In recent years, many stimuli-triggered drug delivery platforms have been designed to deliver drugs accurately to specific sites and reduce their side effects, improving “on-demand” therapeutic efficacy. Adenosine-5'-triphosphate (ATP)-responsive drug delivery methods are examples of these systems that use ATP molecules as a trigger for delivery of therapeutic agents. Since intra- and extra-cellular ATP concentrations are significantly different from each other (1-10 mM and <0.4 mM, respectively), the use of ATP can be a practical method for regulating drug release. Aptamers possess unique properties including, ligand-specific response, short sequence (~ 20-80 bases) and easy functionalization. Thus, their combination with ATP-responsive systems results in more accurate drug delivery systems and greater control of drug release. A wide range of nanoparticle frameworks, such as polymeric nanogels, liposomes, metallic nanoparticles, protein, or DNA nano-assemblies, have been employed in the fabrication of nanocarriers. In this review, we describe several ATP-responsive drug delivery systems based on the various carriers and discuss the challenges and strengths of each method.","PeriodicalId":8928,"journal":{"name":"Biomaterials eJournal","volume":"68 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84950497","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}
Y. Zhou, Q. Yang, Yingfun Yan, Luzhong Zhang, Jin-bo Tang
Tendon injuries are more common, and due to the lack of adequate growth factors, the healing capacity of the injured tendon is limited. The objective of this study is to evaluate the effectiveness of Nanoparticle-coated sutures carrying growth factors on accelerating tendon repair. We found that nanoparticles can adhere uniformly to the surface of the suture modified with polydopamine. After stitching, the nanoparticles remain on the surface of the suture, and its loaded proteins can spread in the tendon tissues. After treatment, in the chicken flexor tendon healing model and the rat Achilles healing model, the ultimate strengths of repaired tendons treated with bFGF and VEGFA-releasing sutures was significantly greater than the tendons repaired with control sutures at multiple time-points. At 6 weeks, adhesion scores in the bFGF and VEGFA-releasing suture group were significantly smaller than those of the control suture group. Tendon gliding excursions were significantly greater in the bFGF and VEGFA-releasing suture group than in the unmodified control sutures. Work of digital flexion was significantly decreased in the bFGF and VEGFA-releasing suture group than in the control group. In a word, we developed a novel platform for local and sustained delivery of growth factors based on the Nanoparticle-coated sutures, which can effectively deliver growth factors to tissues and control the release of growth factors. Dual growth factors loaded Nanoparticle-coated sutures can significantly promote tendon healing. This growth factors delivery system is an attractive therapeutic tool to repair injured tendons.
{"title":"Nanoparticle-Coated Sutures Providing Sustained Growth Factor Delivery to Improve the Healing Strengths of Injured Tendons","authors":"Y. Zhou, Q. Yang, Yingfun Yan, Luzhong Zhang, Jin-bo Tang","doi":"10.2139/ssrn.3676764","DOIUrl":"https://doi.org/10.2139/ssrn.3676764","url":null,"abstract":"Tendon injuries are more common, and due to the lack of adequate growth factors, the healing capacity of the injured tendon is limited. The objective of this study is to evaluate the effectiveness of Nanoparticle-coated sutures carrying growth factors on accelerating tendon repair. We found that nanoparticles can adhere uniformly to the surface of the suture modified with polydopamine. After stitching, the nanoparticles remain on the surface of the suture, and its loaded proteins can spread in the tendon tissues. After treatment, in the chicken flexor tendon healing model and the rat Achilles healing model, the ultimate strengths of repaired tendons treated with bFGF and VEGFA-releasing sutures was significantly greater than the tendons repaired with control sutures at multiple time-points. At 6 weeks, adhesion scores in the bFGF and VEGFA-releasing suture group were significantly smaller than those of the control suture group. Tendon gliding excursions were significantly greater in the bFGF and VEGFA-releasing suture group than in the unmodified control sutures. Work of digital flexion was significantly decreased in the bFGF and VEGFA-releasing suture group than in the control group. In a word, we developed a novel platform for local and sustained delivery of growth factors based on the Nanoparticle-coated sutures, which can effectively deliver growth factors to tissues and control the release of growth factors. Dual growth factors loaded Nanoparticle-coated sutures can significantly promote tendon healing. This growth factors delivery system is an attractive therapeutic tool to repair injured tendons.","PeriodicalId":8928,"journal":{"name":"Biomaterials eJournal","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80326424","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}
O. T. Beek, M. Gelder, C. Lokhorst, Diënty H. M. Hazenbrink, B. H. Lentferink, K. Gerritsen, D. Stamatialis
Hemodialysis mainly removes small water-soluble uremic toxins but cannot effectively remove middle molecules and protein-bound uremic toxins. Besides, the therapy is intermittent leading to fluctuating blood values and fluid status which adversely impacts patients’ health. Prolonged hemodialysis could improve the removal of toxins and the development of portable and wearable artificial kidneys could offer more flexibility in the dialysis scheme. This would enhance patients’ overall health, autonomy, mobility and flexibility, allowing patients to participate in social and economic life. However, during prolonged hemodialysis, blood clots could obstruct the fiber lumen, resulting in a decrease of the effective membrane surface area available for toxin removal. The outside-in filtration (OIF) mode, wherein blood flows through the inter-fiber space instead of through the fiber lumina, has been applied widely in blood oxygenators to prevent fiber clotting, but not in hemodialysis. In this study, we present for the first time the development of a mixed matrix membrane (MMM) for OIF of human blood plasma. This MMM combines diffusion and adsorption and consists of a polymeric membrane matrix with activated carbon (AC) particles on the inside layer, and a polymeric particle-free layer on the outer fiber layer. Our results show that in vitro MMM fibers for OIF demonstrate superior removal of the protein-bound uremic toxins, indoxyl sulfate and hippuric acid, compared to both earlier MMM fibers designed for inside-out filtration mode and commercial high-flux fibers.
{"title":"Dual Layer Mixed Matrix Hollow Fiber Membranes for Outside-In Filtration of Human Blood Plasma","authors":"O. T. Beek, M. Gelder, C. Lokhorst, Diënty H. M. Hazenbrink, B. H. Lentferink, K. Gerritsen, D. Stamatialis","doi":"10.2139/ssrn.3676727","DOIUrl":"https://doi.org/10.2139/ssrn.3676727","url":null,"abstract":"Hemodialysis mainly removes small water-soluble uremic toxins but cannot effectively remove middle molecules and protein-bound uremic toxins. Besides, the therapy is intermittent leading to fluctuating blood values and fluid status which adversely impacts patients’ health. Prolonged hemodialysis could improve the removal of toxins and the development of portable and wearable artificial kidneys could offer more flexibility in the dialysis scheme. This would enhance patients’ overall health, autonomy, mobility and flexibility, allowing patients to participate in social and economic life. However, during prolonged hemodialysis, blood clots could obstruct the fiber lumen, resulting in a decrease of the effective membrane surface area available for toxin removal. The outside-in filtration (OIF) mode, wherein blood flows through the inter-fiber space instead of through the fiber lumina, has been applied widely in blood oxygenators to prevent fiber clotting, but not in hemodialysis. In this study, we present for the first time the development of a mixed matrix membrane (MMM) for OIF of human blood plasma. This MMM combines diffusion and adsorption and consists of a polymeric membrane matrix with activated carbon (AC) particles on the inside layer, and a polymeric particle-free layer on the outer fiber layer. Our results show that in vitro MMM fibers for OIF demonstrate superior removal of the protein-bound uremic toxins, indoxyl sulfate and hippuric acid, compared to both earlier MMM fibers designed for inside-out filtration mode and commercial high-flux fibers.","PeriodicalId":8928,"journal":{"name":"Biomaterials eJournal","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90530506","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：