{"title":"Silk fibroin promotes H3K9me3 expression and chromatin reorganization to regulate endothelial cell proliferation.","authors":"Kaixiang Gao, Yafan Xie, Fangning Xu, Qin Peng, Li Fu, Guixue Wang, Juhui Qiu","doi":"10.1063/5.0203858","DOIUrl":"10.1063/5.0203858","url":null,"abstract":"<p><p>Silk fibroin (SF), which is extensively utilized in tissue engineering and vascular grafts for enhancing vascular regeneration, has not been thoroughly investigated for its epigenetic effects on endothelial cells (EC). This study employed RNA sequencing analysis to evaluate the activation of histone modification regulatory genes in EC treated with SF. Subsequent investigations revealed elevated H3K9me3 levels in SF-treated EC, as evidenced by immunofluorescence and western blot analysis. The study utilized H2B-eGFP endothelial cells to demonstrate that SF treatment results in the accumulation of H2B-marked chromatin in the nuclear inner cavities of EC. Inhibition of H3K9me3 levels by a histone deacetylase inhibitor TSA decreased cell proliferation. Furthermore, the activation of the MAPK signaling pathway using chromium picolinate decreased the proliferative activity and H3K9me3 level in SF-treated EC. SF also appeared to enhance cell growth and proliferation by modulating the H3K9me3 level and reorganizing chromatin, particularly after oxidative stress induced by H<sub>2</sub>O<sub>2</sub> treatment. In summary, these findings indicate that SF promotes EC proliferation by increasing the H3K9me3 level even under stress conditions.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 2","pages":"026115"},"PeriodicalIF":6.0,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11143938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
APL BioengineeringPub Date : 2024-05-29eCollection Date: 2024-06-01DOI: 10.1063/5.0204201
Alessandro Gulotta, Saskia Bucciarelli, Felix Roosen-Runge, Olaf Holderer, Peter Schurtenberger, Anna Stradner
{"title":"Testing mixing rules for structural and dynamical quantities in multi-component crowded protein solutions.","authors":"Alessandro Gulotta, Saskia Bucciarelli, Felix Roosen-Runge, Olaf Holderer, Peter Schurtenberger, Anna Stradner","doi":"10.1063/5.0204201","DOIUrl":"10.1063/5.0204201","url":null,"abstract":"<p><p>Crowding effects significantly influence the phase behavior and the structural and dynamic properties of the concentrated protein mixtures present in the cytoplasm of cells or in the blood serum. This poses enormous difficulties for our theoretical understanding and our ability to predict the behavior of these systems. While the use of course grained colloid-inspired models allows us to reproduce the key physical solution properties of concentrated monodisperse solutions of individual proteins, we lack corresponding theories for complex polydisperse mixtures. Here, we test the applicability of simple mixing rules in order to predict solution properties of protein mixtures. We use binary mixtures of the well-characterized bovine eye lens proteins <i>α</i> and <i>γ<sub>B</sub></i> crystallin as model systems. Combining microrheology with static and dynamic scattering techniques and observations of the phase diagram for liquid-liquid phase separation, we show that reasonably accurate descriptions are possible for macroscopic and mesoscopic signatures, while information on the length scale of the individual protein size requires more information on cross-component interaction.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 2","pages":"026116"},"PeriodicalIF":6.0,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11143939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
APL BioengineeringPub Date : 2024-05-28eCollection Date: 2024-06-01DOI: 10.1063/5.0209537
Yael Hanein, Josef Goding
{"title":"Guest Editorial: Implantable bioelectronics.","authors":"Yael Hanein, Josef Goding","doi":"10.1063/5.0209537","DOIUrl":"10.1063/5.0209537","url":null,"abstract":"<p><p>The realm of implantable bioelectronics represents a frontier in medical science, merging technology, biology, and medicine to innovate treatments that enhance, restore, or monitor physiological functions. This field has yielded devices like cochlear implants, cardiac pacemakers, deep brain stimulators, and vagus nerve stimulators, each designed to address a specific health condition, ranging from sensorineural hearing loss to chronic pain, neurological disorders, and heart rhythm irregularities. Such devices underscore the potential of bioelectronics to significantly improve patient outcomes and quality of life. Recent technological breakthroughs in materials science, nanotechnology, and microfabrication have enabled the development of more sophisticated, smaller, and biocompatible bioelectronic devices. However, the field also encounters challenges, particularly in extending the capabilities of devices such as retinal prostheses, which aim to restore vision but currently offer limited visual acuity. Research in implantable bioelectronics is highly timely, driven by an aging global population with a growing prevalence of chronic diseases that could benefit from these technologies. The convergence of societal health needs, advancing technological capabilities, and a supportive ecosystem for innovation marks this era as pivotal for bioelectronic research.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 2","pages":"020401"},"PeriodicalIF":6.0,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11136517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141176387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
APL BioengineeringPub Date : 2024-05-28eCollection Date: 2024-06-01DOI: 10.1063/5.0203653
Maria Rocchi, Konstantina Papangelopoulou, Marcus Ingram, Youri Bekhuis, Guido Claessen, Piet Claus, Jan D'hooge, Dirk W Donker, Bart Meyns, Libera Fresiello
{"title":"A patient-specific echogenic soft robotic left ventricle embedded into a closed-loop cardiovascular simulator for advanced device testing.","authors":"Maria Rocchi, Konstantina Papangelopoulou, Marcus Ingram, Youri Bekhuis, Guido Claessen, Piet Claus, Jan D'hooge, Dirk W Donker, Bart Meyns, Libera Fresiello","doi":"10.1063/5.0203653","DOIUrl":"10.1063/5.0203653","url":null,"abstract":"<p><p>Cardiovascular medical devices undergo a large number of pre- and post-market tests before their approval for clinical practice use. Sophisticated cardiovascular simulators can significantly expedite the evaluation process by providing a safe and controlled environment and representing clinically relevant case scenarios. The complex nature of the cardiovascular system affected by severe pathologies and the inherently intricate patient-device interaction creates a need for high-fidelity test benches able to reproduce intra- and inter-patient variability of disease states. Therefore, we propose an innovative cardiovascular simulator that combines <i>in silico</i> and <i>in vitro</i> modeling techniques with a soft robotic left ventricle. The simulator leverages patient-specific and echogenic soft robotic phantoms used to recreate the intracardiac pressure and volume waveforms, combined with an <i>in silico</i> lumped parameter model of the remaining cardiovascular system. Three different patient-specific profiles were recreated, to assess the capability of the simulator to represent a variety of working conditions and mechanical properties of the left ventricle. The simulator is shown to provide a realistic physiological and anatomical representation thanks to the use of soft robotics combined with <i>in silico</i> modeling. This tool proves valuable for optimizing and validating medical devices and delineating specific indications and boundary conditions.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 2","pages":"026114"},"PeriodicalIF":6.6,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11136518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141176352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
APL BioengineeringPub Date : 2024-05-07eCollection Date: 2024-06-01DOI: 10.1063/5.0187974
Pamela C Cai, Margaret Braunreuther, Audrey Shih, Andrew J Spakowitz, Gerald G Fuller, Sarah C Heilshorn
{"title":"Air-liquid intestinal cell culture allows <i>in situ</i> rheological characterization of intestinal mucus.","authors":"Pamela C Cai, Margaret Braunreuther, Audrey Shih, Andrew J Spakowitz, Gerald G Fuller, Sarah C Heilshorn","doi":"10.1063/5.0187974","DOIUrl":"10.1063/5.0187974","url":null,"abstract":"<p><p>Intestinal health heavily depends on establishing a mucus layer within the gut with physical properties that strike a balance between being sufficiently elastic to keep out harmful pathogens yet viscous enough to flow and turnover the contents being digested. Studies investigating dysfunction of the mucus layer in the intestines are largely confined to animal models, which require invasive procedures to collect the mucus fluid. In this work, we develop a nondestructive method to study intestinal mucus. We use an air-liquid interface culture of primary human intestinal epithelial cells that exposes their apical surface to allow <i>in situ</i> analysis of the mucus layer. Mucus collection is not only invasive but also disrupts the mucus microstructure, which plays a crucial role in the interaction between mucus and the gut microbiome. Therefore, we leverage a noninvasive rheology technique that probes the mechanical properties of the mucus without removal from the culture. Finally, to demonstrate biomedical uses for this cell culture system, we characterize the biochemical and biophysical properties of intestinal mucus due to addition of the cytokine IL-13 to recapitulate the gut environment of <i>Nippostrongylus brasiliensis</i> infection.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 2","pages":"026112"},"PeriodicalIF":6.6,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11078553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
APL BioengineeringPub Date : 2024-03-28eCollection Date: 2024-03-01DOI: 10.1063/5.0189222
Kylie J Trettner, Jeremy Hsieh, Weikun Xiao, Jerry S H Lee, Andrea M Armani
{"title":"Nondestructive, quantitative viability analysis of 3D tissue cultures using machine learning image segmentation.","authors":"Kylie J Trettner, Jeremy Hsieh, Weikun Xiao, Jerry S H Lee, Andrea M Armani","doi":"10.1063/5.0189222","DOIUrl":"10.1063/5.0189222","url":null,"abstract":"<p><p>Ascertaining the collective viability of cells in different cell culture conditions has typically relied on averaging colorimetric indicators and is often reported out in simple binary readouts. Recent research has combined viability assessment techniques with image-based deep-learning models to automate the characterization of cellular properties. However, further development of viability measurements to assess the continuity of possible cellular states and responses to perturbation across cell culture conditions is needed. In this work, we demonstrate an image processing algorithm for quantifying features associated with cellular viability in 3D cultures without the need for assay-based indicators. We show that our algorithm performs similarly to a pair of human experts in whole-well images over a range of days and culture matrix compositions. To demonstrate potential utility, we perform a longitudinal study investigating the impact of a known therapeutic on pancreatic cancer spheroids. Using images taken with a high content imaging system, the algorithm successfully tracks viability at the individual spheroid and whole-well level. The method we propose reduces analysis time by 97% in comparison with the experts. Because the method is independent of the microscope or imaging system used, this approach lays the foundation for accelerating progress in and for improving the robustness and reproducibility of 3D culture analysis across biological and clinical research.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 1","pages":"016121"},"PeriodicalIF":6.6,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10985731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140872559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
APL BioengineeringPub Date : 2024-03-19eCollection Date: 2024-03-01DOI: 10.1063/5.0207818
L Vítková, N Kazantseva, L Musilová, P Smolka, K Valášková, K Kocourková, M Humeník, A Minařík, P Humpolíček, A Mráček, I Smolková
{"title":"Erratum: Publisher's Note: \"Magneto-responsive hyaluronan hydrogel for hyperthermia and bioprinting: Magnetic, rheological properties and biocompatibility\" [APL Bioeng. <b>7</b>, 036113 (2023)].","authors":"L Vítková, N Kazantseva, L Musilová, P Smolka, K Valášková, K Kocourková, M Humeník, A Minařík, P Humpolíček, A Mráček, I Smolková","doi":"10.1063/5.0207818","DOIUrl":"https://doi.org/10.1063/5.0207818","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1063/5.0147181.].</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 1","pages":"019901"},"PeriodicalIF":6.0,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10954346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140177067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
APL BioengineeringPub Date : 2024-03-19eCollection Date: 2024-03-01DOI: 10.1063/5.0188238
Naveen R Natesh, Pankaj Mogha, Alan Chen, Scott J Antonia, Shyni Varghese
{"title":"Differential roles of normal and lung cancer-associated fibroblasts in microvascular network formation.","authors":"Naveen R Natesh, Pankaj Mogha, Alan Chen, Scott J Antonia, Shyni Varghese","doi":"10.1063/5.0188238","DOIUrl":"10.1063/5.0188238","url":null,"abstract":"<p><p>Perfusable microvascular networks offer promising three-dimensional <i>in vitro</i> models to study normal and compromised vascular tissues as well as phenomena such as cancer cell metastasis. Engineering of these microvascular networks generally involves the use of endothelial cells stabilized by fibroblasts to generate robust and stable vasculature. However, fibroblasts are highly heterogenous and may contribute variably to the microvascular structure. Here, we study the effect of normal and cancer-associated lung fibroblasts on the formation and function of perfusable microvascular networks. We examine the influence of cancer-associated fibroblasts on microvascular networks when cultured in direct (juxtacrine) and indirect (paracrine) contacts with endothelial cells, discovering a generative inhibition of microvasculature in juxtacrine co-cultures and a functional inhibition in paracrine co-cultures. Furthermore, we probed the secreted factors differential between cancer-associated fibroblasts and normal human lung fibroblasts, identifying several cytokines putatively influencing the resulting microvasculature morphology and functionality. These findings suggest the potential contribution of cancer-associated fibroblasts in aberrant microvasculature associated with tumors and the plausible application of such <i>in vitro</i> platforms in identifying new therapeutic targets and/or agents that can prevent formation of aberrant vascular structures.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 1","pages":"016120"},"PeriodicalIF":6.0,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10959556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140207857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
APL BioengineeringPub Date : 2024-03-14eCollection Date: 2024-03-01DOI: 10.1063/5.0189401
Zeina Hachem, Courtney Hadrian, Lina Aldbaisi, Muslim Alkaabi, Leo Q Wan, Jie Fan
{"title":"Asymmetrical positioning of cell organelles reflects the cell chirality of mouse myoblast cells.","authors":"Zeina Hachem, Courtney Hadrian, Lina Aldbaisi, Muslim Alkaabi, Leo Q Wan, Jie Fan","doi":"10.1063/5.0189401","DOIUrl":"10.1063/5.0189401","url":null,"abstract":"<p><p>Cell chirality is crucial for the chiral morphogenesis of biological tissues, yet its underlying mechanism remains unclear. Cell organelle polarization along multiple axes in a cell body, namely, apical-basal, front-rear, and left-right, is known to direct cell behavior such as orientation, rotation, and migration. Among these axes, the left-right bias holds significant sway in determining the chiral directionality of these behaviors. Normally, mouse myoblast (C2C12) cells exhibit a strong counterclockwise chirality on a ring-shaped micropattern, whereas they display a clockwise dominant chirality under Latrunculin A treatment. To investigate the relationship between multicellular chirality and organelle positioning in single cells, we studied the left-right positioning of cell organelles under distinct cell chirality in single cells via micropatterning technique, fluorescent microscopy, and imaging analysis. We found that on a \"T\"-shaped micropattern, a C2C12 cell adopts a triangular shape, with its nucleus-centrosome axis pointing toward the top-right direction of the \"T.\" Several other organelles, including the Golgi apparatus, lysosomes, actin filaments, and microtubules, showed a preference to polarize on one side of the axis, indicating the universality of the left-right asymmetrical organelle positioning. Interestingly, upon reversing cell chirality with Latrunculin A, the organelles correspondingly reversed their left-right positioning bias, as suggested by the consistently biased metabolism and contractile properties at the leading edge. This left-right asymmetry in organelle positioning may help predict cell migration direction and serve as a potential marker for identifying cell chirality in biological models.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 1","pages":"016119"},"PeriodicalIF":6.0,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10942803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140144278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
APL BioengineeringPub Date : 2024-03-13eCollection Date: 2024-03-01DOI: 10.1063/5.0191803
Wenjing Xie, Chao Song, Ruowen Guo, Xin Zhang
{"title":"Static magnetic fields in regenerative medicine.","authors":"Wenjing Xie, Chao Song, Ruowen Guo, Xin Zhang","doi":"10.1063/5.0191803","DOIUrl":"10.1063/5.0191803","url":null,"abstract":"<p><p>All organisms on Earth live in the weak but ubiquitous geomagnetic field. Human beings are also exposed to magnetic fields generated by multiple sources, ranging from permanent magnets to magnetic resonance imaging (MRI) in hospitals. It has been shown that different magnetic fields can generate various effects on different tissues and cells. Among them, stem cells appear to be one of the most sensitive cell types to magnetic fields, which are the fundamental units of regenerative therapies. In this review, we focus on the bioeffects of static magnetic fields (SMFs), which are related to regenerative medicine. Most reports in the literature focus on the influence of SMF on bone regeneration, wound healing, and stem cell production. Multiple aspects of the cellular events, including gene expression, cell signaling pathways, reactive oxygen species, inflammation, and cytoskeleton, have been shown to be affected by SMFs. Although no consensus yet, current evidence indicates that moderate and high SMFs could serve as a promising physical tool to promote bone regeneration, wound healing, neural differentiation, and dental regeneration. All <i>in vivo</i> studies of SMFs on bone regeneration and wound healing have shown beneficial effects, which unravel the great potential of SMFs in these aspects. More mechanistic studies, magnetic field parameter optimization, and clinical investigations on human bodies will be imperative for the successful clinical applications of SMFs in regenerative medicine.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 1","pages":"011503"},"PeriodicalIF":6.0,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10939708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140132792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}