Amadeus S. Zhu, Tasneem Mustafa, K. J. Grande-Allen
Mitral valve disease is a major cause of cardiovascular morbidity throughout the world. Many different mitral valve pathologies demonstrate a pronounced degree of fibrotic remodeling, often accompanied by an inflammatory state. Mitral valve fibrosis is mediated by valvular interstitial cells (VICs), which reside in the valve leaflets and show a tendency to differentiate into myofibroblast-like cells during disease conditions. In this study, we investigated the effects of tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) on mitral VICs, since these pro-inflammatory cytokines have been shown to exert pleiotropic effects on various cell types in other fibrotic disorders. Using biomimetic three-dimensional culture systems, we demonstrated that TNF-α and IL-1β suppress myofibroblast differentiation in mitral VICs, as evidenced by gene and protein expression of alpha smooth muscle actin and smooth muscle 22 alpha. Addition of TNF-α and IL-1β also inhibited mitral VIC-mediated contraction of collagen gels. Furthermore, inhibition of NF-κB, which is downstream of TNF-α and IL-1β, reversed these effects. These results reveal targetable pathways that could enable the development of pharmaceutical treatments for alleviating fibrosis during mitral valve disease.
{"title":"Tumor Necrosis Factor Alpha and Interleukin 1 Beta Suppress Myofibroblast Activation Via Nuclear Factor Kappa B Signaling in 3D-Cultured Mitral Valve Interstitial Cells","authors":"Amadeus S. Zhu, Tasneem Mustafa, K. J. Grande-Allen","doi":"10.2139/ssrn.3718052","DOIUrl":"https://doi.org/10.2139/ssrn.3718052","url":null,"abstract":"Mitral valve disease is a major cause of cardiovascular morbidity throughout the world. Many different mitral valve pathologies demonstrate a pronounced degree of fibrotic remodeling, often accompanied by an inflammatory state. Mitral valve fibrosis is mediated by valvular interstitial cells (VICs), which reside in the valve leaflets and show a tendency to differentiate into myofibroblast-like cells during disease conditions. In this study, we investigated the effects of tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) on mitral VICs, since these pro-inflammatory cytokines have been shown to exert pleiotropic effects on various cell types in other fibrotic disorders. Using biomimetic three-dimensional culture systems, we demonstrated that TNF-α and IL-1β suppress myofibroblast differentiation in mitral VICs, as evidenced by gene and protein expression of alpha smooth muscle actin and smooth muscle 22 alpha. Addition of TNF-α and IL-1β also inhibited mitral VIC-mediated contraction of collagen gels. Furthermore, inhibition of NF-κB, which is downstream of TNF-α and IL-1β, reversed these effects. These results reveal targetable pathways that could enable the development of pharmaceutical treatments for alleviating fibrosis during mitral valve disease.","PeriodicalId":118406,"journal":{"name":"BioRN: Biomimetics (Topic)","volume":"188 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132353317","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}
Nayeon Lee, Z. Liu, Sungkwang Mun, K. Johnson, M. Horstemeyer
This study investigates the role of ridges of ram horns with regard to damping of mechanical impacts arising from ramming. We measured ram horn ridges from eight specimens of six different species and analyzed the ridges’ pitch distributions. Also, using finite element analysis, a ridged horn model was compared with a non-ridged horn model. The results demonstrate three functions of ram horn ridges; 1) transferring longitudinal waves to shear waves, 2) filtering out shear waves, and 3) stabilizing structures by reducing excessive strain.
{"title":"The Function of Horn Ridges for Impact Damping","authors":"Nayeon Lee, Z. Liu, Sungkwang Mun, K. Johnson, M. Horstemeyer","doi":"10.2139/ssrn.3322822","DOIUrl":"https://doi.org/10.2139/ssrn.3322822","url":null,"abstract":"This study investigates the role of ridges of ram horns with regard to damping of mechanical impacts arising from ramming. We measured ram horn ridges from eight specimens of six different species and analyzed the ridges’ pitch distributions. Also, using finite element analysis, a ridged horn model was compared with a non-ridged horn model. The results demonstrate three functions of ram horn ridges; 1) transferring longitudinal waves to shear waves, 2) filtering out shear waves, and 3) stabilizing structures by reducing excessive strain.","PeriodicalId":118406,"journal":{"name":"BioRN: Biomimetics (Topic)","volume":"10 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133479374","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}
Claire E. Tomaszewski, K. DiLillo, Brendon M. Baker, K. Arnold, A. Shikanov
Synthetic matrices offer a high degree of control and tunability for mimicking extracellular matrix functions of native tissue, allowing the study of disease and development in vitro. In this study, we functionalized degradable poly(ethylene glycol) hydrogels with extracellular matrix (ECM)-sequestering peptides aiming to recapitulate the native ECM composition for culture and maturation of ovarian follicular organoids. We hypothesized that ECM-sequestering peptides would facilitate deposition and retention of cell-secreted ECM molecules, thereby recreating cell-matrix interactions in otherwise bioinert PEG hydrogels. Specifically, heparin-binding peptide from antithrombin III (HBP), heparan sulfate binding peptide derived from laminin (AG73), basement membrane binder peptide (BMB), and heparan sulfate binding region of placental growth factor 2 (RRR) tethered to a PEG hydrogel significantly improved follicle survival, growth and maturation compared to PEG-Cys, a mechanically similar but biologically inert control. Immunohistochemical analysis of the hydrogel surrounding cultured follicles confirmed sequestration and retention of laminin, collagen I, perlecan and fibronectin in ECM-sequestering hydrogels but not in bioinert PEG-Cys hydrogels. The media from follicles cultured in PEG-AG73, PEG-BMB, and PEG-RRR also had significantly higher concentrations of factors known to regulate follicle development compared to PEG-Cys. PEG-AG73 and PEG-BMB were the most beneficial for promoting follicle maturation, likely because AG73 and BMB mimic basement membrane interactions which are crucial for follicle development. Here we have shown that functionalizing PEG with ECM-sequestering peptides allows cell-secreted ECM to be retained within the hydrogels, restoring critical cell-matrix interactions and promoting healthy organoid development in a fully synthetic culture system.
{"title":"Sequestered Cell-Secreted Extracellular Matrix Proteins Improve Folliculogenesis and Oocyte Maturation for Fertility Preservation","authors":"Claire E. Tomaszewski, K. DiLillo, Brendon M. Baker, K. Arnold, A. Shikanov","doi":"10.2139/ssrn.3720978","DOIUrl":"https://doi.org/10.2139/ssrn.3720978","url":null,"abstract":"Synthetic matrices offer a high degree of control and tunability for mimicking extracellular matrix functions of native tissue, allowing the study of disease and development <i>in vitro</i>. In this study, we functionalized degradable poly(ethylene glycol) hydrogels with extracellular matrix (ECM)-sequestering peptides aiming to recapitulate the native ECM composition for culture and maturation of ovarian follicular organoids. We hypothesized that ECM-sequestering peptides would facilitate deposition and retention of cell-secreted ECM molecules, thereby recreating cell-matrix interactions in otherwise bioinert PEG hydrogels. Specifically, heparin-binding peptide from antithrombin III (HBP), heparan sulfate binding peptide derived from laminin (AG73), basement membrane binder peptide (BMB), and heparan sulfate binding region of placental growth factor 2 (RRR) tethered to a PEG hydrogel significantly improved follicle survival, growth and maturation compared to PEG-<i><b>Cys</b></i>, a mechanically similar but biologically inert control. Immunohistochemical analysis of the hydrogel surrounding cultured follicles confirmed sequestration and retention of laminin, collagen I, perlecan and fibronectin in ECM-sequestering hydrogels but not in bioinert PEG-<i><b>Cys</b></i> hydrogels. The media from follicles cultured in PEG-<i><b>AG73</b></i>, PEG-<i><b>BMB</b></i>, and PEG-<i><b>RRR</b></i> also had significantly higher concentrations of factors known to regulate follicle development compared to PEG-<i><b>Cys</b></i>. PEG-<i><b>AG73</b></i> and PEG-<i><b>BMB</b></i> were the most beneficial for promoting follicle maturation, likely because AG73 and BMB mimic basement membrane interactions which are crucial for follicle development. Here we have shown that functionalizing PEG with ECM-sequestering peptides allows cell-secreted ECM to be retained within the hydrogels, restoring critical cell-matrix interactions and promoting healthy organoid development in a fully synthetic culture system.","PeriodicalId":118406,"journal":{"name":"BioRN: Biomimetics (Topic)","volume":"35 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":"126815236","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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