{"title":"Antimicrobial-free graphene nanocoating decreases fungal yeast-to-hyphal switching and maturation of cross-kingdom biofilms containing clinical and antibiotic-resistant bacteria","authors":"Shruti Vidhawan Agarwalla , Kassapa Ellepola , Vitaly Sorokin , Mario Ihsan , Nikolaos Silikas , AH Castro Neto , Chaminda Jayampath Seneviratne , Vinicius Rosa","doi":"10.1016/j.bbiosy.2022.100069","DOIUrl":"10.1016/j.bbiosy.2022.100069","url":null,"abstract":"<div><p><em>Candida albicans</em> and methicillin-resistant <em>Staphylococcus aureus</em> (<em>MRSA</em>) synergize in cross-kingdom biofilms to increase the risk of mortality and morbidity due to high resistance to immune and antimicrobial defenses. Biomedical devices and implants made with titanium are vulnerable to infections that may demand their surgical removal from the infected sites. Graphene nanocoating (GN) has promising anti-adhesive properties against <em>C. albicans</em>. Thus, we hypothesized that GN could prevent fungal yeast-to-hyphal switching and the development of cross-kingdom biofilms. Herein, titanium (Control) was coated with high-quality GN (coverage > 99%). Thereafter, mixed-species biofilms (<em>C. albicans</em> combined with <em>S. aureus</em> or <em>MRSA</em>) were allowed to develop on GN and Control. There were significant reductions in the number of viable cells, metabolic activity, and biofilm biomass on GN compared with the Control (CFU counting, XTT reduction, and crystal violet assays). Also, biofilms on GN were sparse and fragmented, whereas the Control presented several bacterial cells co-aggregating with intertwined hyphal elements (confocal and scanning electronic microscopy). Finally, GN did not induce hemolysis, an essential characteristic for blood-contacting biomaterials and devices. Thus, GN significantly inhibited the formation and maturation of deadly cross-kingdom biofilms, which can be advantageous to avoid infection and surgical removal of infected devices.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"8 ","pages":"Article 100069"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1d/f0/main.PMC9934433.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10762299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matthijs Snelders , Iris H. Koedijk , Julia Schirmer , Otto Mulleners , Juancito van Leeuwen , Nathalie P. de Wagenaar , Oscar Bartulos , Pieter Voskamp , Stefan Braam , Zeno Guttenberg , A.H. Jan Danser , Danielle Majoor-Krakauer , Erik Meijering , Ingrid van der Pluijm , Jeroen Essers
{"title":"Contraction pressure analysis using optical imaging in normal and MYBPC3-mutated hiPSC-derived cardiomyocytes grown on matrices with tunable stiffness","authors":"Matthijs Snelders , Iris H. Koedijk , Julia Schirmer , Otto Mulleners , Juancito van Leeuwen , Nathalie P. de Wagenaar , Oscar Bartulos , Pieter Voskamp , Stefan Braam , Zeno Guttenberg , A.H. Jan Danser , Danielle Majoor-Krakauer , Erik Meijering , Ingrid van der Pluijm , Jeroen Essers","doi":"10.1016/j.bbiosy.2022.100068","DOIUrl":"10.1016/j.bbiosy.2022.100068","url":null,"abstract":"<div><p>Current <em>in vivo</em> disease models and analysis methods for cardiac drug development have been insufficient in providing accurate and reliable predictions of drug efficacy and safety. Here, we propose a custom optical flow-based analysis method to quantitatively measure recordings of contracting cardiomyocytes on polydimethylsiloxane (PDMS), compatible with medium-throughput systems.</p><p>Movement of the PDMS was examined by covalently bound fluorescent beads on the PDMS surface, differences caused by increased substrate stiffness were compared, and cells were stimulated with β-agonist. We further validated the system using cardiomyocytes treated with endothelin-1 and compared their contractions against control and cells incubated with receptor antagonist bosentan. After validation we examined two MYBPC3-mutant patient-derived cell lines.</p><p>Recordings showed that higher substrate stiffness resulted in higher contractile pressure, while beating frequency remained similar to control. β-agonist stimulation resulted in both higher beating frequency as well as higher pressure values during contraction and relaxation. Cells treated with endothelin-1 showed an increased beating frequency, but a lower contraction pressure. Cells treated with both endothelin-1 and bosentan remained at control level of beating frequency and pressure. Lastly, both MYBPC3-mutant lines showed a higher beating frequency and lower contraction pressure.</p><p>Our validated method is capable of automatically quantifying contraction of hiPSC-derived cardiomyocytes on a PDMS substrate of known shear modulus, returning an absolute value. Our method could have major benefits in a medium-throughput setting.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"8 ","pages":"Article 100068"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3a/2b/main.PMC9934435.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10762300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ina Prade , Michaela Schröpfer , Caroline Seidel , Claudia Krumbiegel , Tina Hille , Frank Sonntag , Stephen Behrens , Florian Schmieder , Birgit Voigt , Michael Meyer
{"title":"Human endothelial cells form an endothelium in freestanding collagen hollow filaments fabricated by direct extrusion printing","authors":"Ina Prade , Michaela Schröpfer , Caroline Seidel , Claudia Krumbiegel , Tina Hille , Frank Sonntag , Stephen Behrens , Florian Schmieder , Birgit Voigt , Michael Meyer","doi":"10.1016/j.bbiosy.2022.100067","DOIUrl":"10.1016/j.bbiosy.2022.100067","url":null,"abstract":"<div><p>Fiber-shaped materials have great potential for tissue engineering applications as they provide structural support and spatial patterns within a three-dimensional construct. Here we demonstrate the fabrication of mechanically stable, meter-long collagen hollow filaments by a direct extrusion printing process. The fibres are permeable for oxygen and proteins and allow cultivation of primary human endothelial cells (ECs) at the inner surface under perfused conditions. The cells show typical characteristics of a well-organized EC lining including VE-cadherin expression, cellular response to flow and ECM production. The results demonstrate that the collagen tubes are capable of creating robust soft tissue filaments. The mechanical properties and the biofunctionality of these collagen hollow filaments facilitate the engineering of prevascularised tissue engineering constructs.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"8 ","pages":"Article 100067"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/db/a6/main.PMC9934428.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10769501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Winnie Q. Brandão , Romário J. da Silva , Lizeth C. Mojica-Sánchez , Bruna G. Maciel , Gabriela P. Ratkovski , Celso P. de Melo
{"title":"Use of polypyrrole-polystyrene membranes for extracting DNA from plant tissues","authors":"Winnie Q. Brandão , Romário J. da Silva , Lizeth C. Mojica-Sánchez , Bruna G. Maciel , Gabriela P. Ratkovski , Celso P. de Melo","doi":"10.1016/j.bbiosy.2022.100060","DOIUrl":"10.1016/j.bbiosy.2022.100060","url":null,"abstract":"<div><p>We describe the preparation of a membrane composed of polypyrrole-polystyrene (PPy-PS) and its application in DNA extraction. We adopted the electrospinning technique to prepare polystyrene (PS) membranes, which we used as substrates for incorporating polypyrrole chains through an <em>in situ</em> chemical procedure. As a model system, we initially investigated the use of PPy-PS membranes for the extraction of salmon sperm DNA from aqueous solutions. These studies have shown that the PPy-PS membrane has a maximum adsorption capacity of 236.0 mg of DNA per gram of PPy after 30 min of exposure to a DNA solution (100 mg/L). We incorporated the PPy-PS membranes into centrifugation columns, which we used to carry out experiments for extracting and purification of DNA from curly lettuce leaves. The protocol was initially optimized by first examining the most appropriate concentration of the three components of the lysis buffer (Tris/HCl, NaCl, and EDTA-Na). We then investigated the most adequate volumes of the concentrated surfactant solution (SDS 20%) and that used in the protein and polysaccharide precipitation step (5 M potassium acetate, pH 6.3), factors that directly influence the quality and quantity of the fraction of DNA obtained. For curly lettuce leaves, both in their mature and young stages, the yield and purity of the DNA purified using the PPy-PS membrane were comparable to those obtained using a commercial kit. In both cases, the collected DNA samples presented excellent integrity and quality. These results are suggestive that these composite membranes are competitive with the commercial kits available for the extraction and purification of DNA from plants.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"7 ","pages":"Article 100060"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1e/23/main.PMC9934434.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10762304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Benoit Cox , Patrick Barton , Reiner Class , Hannah Coxhead , Claude Delatour , Eric Gillent , Jamie Henshall , Emre M. Isin , Lloyd King , Jean-Pierre Valentin
{"title":"Setup of human liver-chips integrating 3D models, microwells and a standardized microfluidic platform as proof-of-concept study to support drug evaluation","authors":"Benoit Cox , Patrick Barton , Reiner Class , Hannah Coxhead , Claude Delatour , Eric Gillent , Jamie Henshall , Emre M. Isin , Lloyd King , Jean-Pierre Valentin","doi":"10.1016/j.bbiosy.2022.100054","DOIUrl":"10.1016/j.bbiosy.2022.100054","url":null,"abstract":"<div><p>Human 3D liver microtissues/spheroids are powerful <em>in vitro</em> models to study drug-induced liver injury (DILI) but the small number of cells per spheroid limits the models’ usefulness to study drug metabolism. In this work, we scale up the number of spheroids on both a plate and a standardized organ-chip platform by factor 100 using a basic method which requires only limited technical expertise. We successfully generated up to 100 spheroids using polymer-coated microwells in a 96-well plate (= liver-plate) or organ-chip (= liver-chip). Liver-chips display a comparable cellular CYP3A4 activity, viability, and biomarker expression as liver spheroids for at least one week, while liver-plate cultures display an overall reduced hepatic functionality. To prove its applicability to drug discovery and development, the liver-chip was used to test selected reference compounds. The test system could discriminate toxicity of the DILI-positive compound tolcapone from its less hepatotoxic structural analogue entacapone, using biochemical and morphological readouts. Following incubation with diclofenac, the liver-chips had an increased metabolite formation compared to standard spheroid cultures. In summary, we generated a human liver-chip model using a standardized organ-chip platform which combines up to 100 spheroids and can be used for the evaluation of both drug safety and metabolism.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"7 ","pages":"Article 100054"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/00/c5/main.PMC9934436.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10774015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anders Runge Walther , Nicholas Ditzel , Moustapha Kassem , Morten Østergaard Andersen , Martin Aage Barsøe Hedegaard
{"title":"In vivo non-invasive monitoring of tissue development in 3D printed subcutaneous bone scaffolds using fibre-optic Raman spectroscopy","authors":"Anders Runge Walther , Nicholas Ditzel , Moustapha Kassem , Morten Østergaard Andersen , Martin Aage Barsøe Hedegaard","doi":"10.1016/j.bbiosy.2022.100059","DOIUrl":"10.1016/j.bbiosy.2022.100059","url":null,"abstract":"<div><p>The development of novel biomaterials for regenerative therapy relies on the ability to assess tissue development, quality, and similarity with native tissue types in <em>in vivo</em> experiments. Non-invasive imaging modalities such as X-ray computed tomography offer high spatial resolution but limited biochemical information while histology and biochemical assays are destructive. Raman spectroscopy is a non-invasive, label-free and non-destructive technique widely applied for biochemical characterization. Here we demonstrate the use of fibre-optic Raman spectroscopy for <em>in vivo</em> quantitative monitoring of tissue development in subcutaneous calcium phosphate scaffolds in mice over 16 weeks. Raman spectroscopy was able to quantify the time dependency of different tissue components related to the presence, absence, and quantity of mesenchymal stem cells. Scaffolds seeded with stem cells produced 3–5 times higher amount of collagen-rich extracellular matrix after 16 weeks implantation compared to scaffolds without. These however, showed a 2.5 times higher amount of lipid-rich tissue compared to implants with stem cells. <em>Ex vivo</em> micro-computed tomography and histology showed stem cell mediated collagen and bone development. Histological measures of collagen correlated well with Raman derived quantifications (correlation coefficient <em>in vivo</em> 0.74, <em>ex vivo</em> 0.93). In the absence of stem cells, the scaffolds were largely occupied by adipocytes. The technique developed here could potentially be adapted for a range of small animal experiments for assessing tissue engineering strategies at the biochemical level.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"7 ","pages":"Article 100059"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4e/60/main.PMC9934492.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10774018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zehong Xiang , Xinghua Guan , Zhifang Ma , Qiang Shi , Mikhail Panteleev , Fazly I. Ataullakhanov
{"title":"Bioactive engineered scaffolds based on PCL-PEG-PCL and tumor cell-derived exosomes to minimize the foreign body reaction","authors":"Zehong Xiang , Xinghua Guan , Zhifang Ma , Qiang Shi , Mikhail Panteleev , Fazly I. Ataullakhanov","doi":"10.1016/j.bbiosy.2022.100055","DOIUrl":"10.1016/j.bbiosy.2022.100055","url":null,"abstract":"<div><p>Long-term presence of M1 macrophages causes serious foreign body reaction (FBR), which is the main reason for the failure of biological scaffold integration. Inducing M2 polarization of macrophages near scaffolds to reduce foreign body response has been widely researched. In this work, inspired by the special capability of tumor exosomes in macrophages M2 polarization, we integrate tumor-derived exosomes into biological scaffolds to minimize the FBR. In brief, breast cancer cell-derived exosomes are loaded into polycaprolactone-b-polyethylene glycol-b-polycaprolactone (PCL-PEG-PCL) fiber scaffold through physical adsorption and entrapment to constructed bioactive engineered scaffold. In cellular experiments, we demonstrate bioactive engineered scaffold based on PCL-PEG-PCL and exosomes can promote the transformation of macrophages from M1 to M2 through the PI3K/Akt signaling pathway. In addition, the exosomes release gradually from scaffolds and act on the macrophages around the scaffolds to reduce FBR in a subcutaneous implant mouse model. Compared with PCL-PEG-PCL scaffolds without exosomes, bioactive engineered scaffolds reduce significantly inflammation and fibrosis of tissues around the scaffolds. Therefore, cancer cell-derived exosomes show the potential for constructing engineered scaffolds in inhibiting the excessive inflammation and facilitating tissue formation.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"7 ","pages":"Article 100055"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8d/6c/main.PMC9934494.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10762305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marie P.F. Corradi , Alyanne M. de Haan , Bernard Staumont , Aldert H. Piersma , Liesbet Geris , Raymond H.H. Pieters , Cyrille A.M. Krul , Marc A.T. Teunis
{"title":"Natural language processing in toxicology: Delineating adverse outcome pathways and guiding the application of new approach methodologies","authors":"Marie P.F. Corradi , Alyanne M. de Haan , Bernard Staumont , Aldert H. Piersma , Liesbet Geris , Raymond H.H. Pieters , Cyrille A.M. Krul , Marc A.T. Teunis","doi":"10.1016/j.bbiosy.2022.100061","DOIUrl":"10.1016/j.bbiosy.2022.100061","url":null,"abstract":"<div><p>Adverse Outcome Pathways (AOPs) are conceptual frameworks that tie an initial perturbation (molecular initiating event) to a phenotypic toxicological manifestation (adverse outcome), through a series of steps (key events). They provide therefore a standardized way to map and organize toxicological mechanistic information. As such, AOPs inform on key events underlying toxicity, thus supporting the development of New Approach Methodologies (NAMs), which aim to reduce the use of animal testing for toxicology purposes.</p><p>However, the establishment of a novel AOP relies on the gathering of multiple streams of evidence and information, from available literature to knowledge databases. Often, this information is in the form of free text, also called unstructured text, which is not immediately digestible by a computer. This information is thus both tedious and increasingly time-consuming to process manually with the growing volume of data available. The advancement of machine learning provides alternative solutions to this challenge. To extract and organize information from relevant sources, it seems valuable to employ deep learning Natural Language Processing techniques.</p><p>We review here some of the recent progress in the NLP field, and show how these techniques have already demonstrated value in the biomedical and toxicology areas. We also propose an approach to efficiently and reliably extract and combine relevant toxicological information from text. This data can be used to map underlying mechanisms that lead to toxicological effects and start building quantitative models, in particular AOPs, ultimately allowing animal-free human-based hazard and risk assessment.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"7 ","pages":"Article 100061"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9934466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10762307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Developing a clinical grade human adipose decellularized biomaterial","authors":"Daniel J. Hayes , Jeffrey M Gimble","doi":"10.1016/j.bbiosy.2022.100053","DOIUrl":"10.1016/j.bbiosy.2022.100053","url":null,"abstract":"<div><p>While tissue engineering investigators have appreciated adipose tissue as a repository of stromal/stem cells, they are only now beginning to see its value as a decellularized tissue resource. Independent academic investigators have successfully extracted lipid, genomic DNA and proteins from human fat to create a decellularized extracellular matrix enriched in collagen, glycoproteins, and proteoglycans. Pre-clinical studies have validated its compatibility with stromal/stem cells and its ability to support adipogenesis <em>in vitro</em> and <em>in vivo</em> in both small (murine) and large (porcine) subcutaneous implant models. Furthermore, Phase I safety clinical trials have injected decellularized human adipose tissue scaffolds in human volunteers without incident for periods of up to 127 days. This commentary takes an opinionated look at the under-appreciated but potential benefits of obesity as an increasingly available biomaterial resource.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"7 ","pages":"Article 100053"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6d/2c/main.PMC9934471.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10762302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}