Biomaterials and biosystems最新文献

{"title":"Polycaprolactone-collagen nanofibers loaded with dexamethasone and simvastatin as an osteoinductive and immunocompatible scaffold for bone regeneration applications","authors":"Hilal Ahmad Rather ,&nbsp;Johnna Francis Varghese ,&nbsp;Bindiya Dhimmar ,&nbsp;Umesh C.S. Yadav ,&nbsp;Rajesh Vasita","doi":"10.1016/j.bbiosy.2022.100064","DOIUrl":"10.1016/j.bbiosy.2022.100064","url":null,"abstract":"<div><p>Physiological inflammation has been shown to promote bone regeneration; however, prolonged inflammation impedes the osteogenesis and bone repair process. To overcome the latter we aimed to develop a dual drug delivering nanofibrous scaffold to promote osteogenic differentiation of mesenchymal stromal cells (MSCs) and modulate the pro-inflammatory response of macrophages. The polycaprolactone (PCL)-collagen nanofibrous delivery system incorporating dexamethasone and simvastatin was fabricated by electrospinning process. The morphological analysis and mRNA, as well as protein expression of proinflammatory and anti-inflammatory cytokines in human monocytes (U937 cells), demonstrated the immunocompatibility effect of dual drug-releasing nanofibrous scaffolds. Nitric oxide estimation also demonstrated the anti-inflammatory effect of dual drug releasing scaffolds. The scaffolds demonstrated the osteogenic differentiation of adipose-derived MSCs by enhancing the alkaline phosphatase (ALP) activity and mineral deposition after 17 days of cell culture. The increased expression of Runt-related transcription factor-2 (RUNX-2) and osteocalcin at mRNA and protein levels supported the osteogenic potential of dual drug-loaded fibrous scaffolds. Hence, the results indicate that our fabricated nanofibrous scaffolds exhibit immunomodulatory properties and could be employed for bone regeneration applications after further in-vivo validation.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"8 ","pages":"Article 100064"},"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/63/58/main.PMC9934467.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10761860","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":"Evaluation of a co-culture of rapidly isolated chondrocytes and stem cells seeded on tri-layered collagen-based scaffolds in a caprine osteochondral defect model","authors":"Tanya J. Levingstone ,&nbsp;Eamon J. Sheehy ,&nbsp;Conor J. Moran ,&nbsp;Gráinne M. Cunniffe ,&nbsp;Pedro J. Diaz Payno ,&nbsp;Robert T. Brady ,&nbsp;Henrique V. Almeida ,&nbsp;Simon F. Carroll ,&nbsp;John M. O’Byrne ,&nbsp;Daniel J. Kelly ,&nbsp;Pieter AJ. Brama ,&nbsp;Fergal J. O’ Brien","doi":"10.1016/j.bbiosy.2022.100066","DOIUrl":"10.1016/j.bbiosy.2022.100066","url":null,"abstract":"<div><p>Cartilage has poor regenerative capacity and thus damage to the joint surfaces presents a major clinical challenge. Recent research has focussed on the development of tissue-engineered and cell-based approaches for the treatment of cartilage and osteochondral injuries, with current clinically available cell-based approaches including autologous chondrocyte implantation and matrix-assisted autologous chondrocyte implantation. However, these approaches have significant disadvantages due to the requirement for a two-stage surgical procedure and an in vitro chondrocyte expansion phase which increases logistical challenges, hospital times and costs. In this study, we hypothesized that seeding biomimetic tri-layered scaffolds, with proven regenerative potential, with chondrocyte/infrapatellar fat pad stromal cell co-cultures would improve their regenerative capacity compared to scaffolds implanted cell-free. Rapid cell isolation techniques, without the requirement for long term in vitro culture, were utilised to achieve co-cultures of chondrocytes and stromal cells and thus overcome the limitations of existing cell-based techniques. Cell-free and cell-seeded scaffolds were implanted in osteochondral defects, created within the femoral condyle and trochlear ridge, in a translational large animal goat model. While analysis showed trends towards delayed subchondral bone healing in the cell-seeded scaffold group, by the 12 month timepoint the cell-free and cell-seeded groups yield cartilage and bone tissue with comparable quality and quantity. The results of the study reinforce the potential of the biomimetic tri-layered scaffold to repair joint defects but failed to demonstrate a clear benefit from the addition of the CC/FPMSC co-culture to this scaffold. Taking into consideration the additional cost and complexity associated with the cell-seeded scaffold approach, this study demonstrates that the treatment of osteochondral defects using cell-free tri-layered scaffolds may represent a more prudent clinical approach.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"8 ","pages":"Article 100066"},"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/2d/5b/main.PMC9934472.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10774008","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":"Design considerations of benchtop fluid flow bioreactors for bio-engineered tissue equivalents in vitro","authors":"H.W. Hoyle ,&nbsp;C.M.L. Stenger ,&nbsp;S.A. Przyborski","doi":"10.1016/j.bbiosy.2022.100063","DOIUrl":"https://doi.org/10.1016/j.bbiosy.2022.100063","url":null,"abstract":"<div><p>One of the major aims of bio-engineering tissue equivalents <em>in vitro</em> is to create physiologically relevant culture conditions to accurately recreate the cellular microenvironment. This often includes incorporation of factors such as the extracellular matrix, co-culture of multiple cell types and three-dimensional culture techniques. These advanced techniques can recapitulate some of the properties of tissue <em>in vivo</em>, however fluid flow is a key aspect that is often absent. Fluid flow can be introduced into cell and tissue culture using bioreactors, which are becoming increasingly common as we seek to produce increasingly accurate tissue models. Bespoke technology is continuously being developed to tailor systems for specific applications and to allow compatibility with a range of culture techniques. For effective perfusion of a tissue culture many parameters can be controlled, ranging from impacts of the fluid flow such as increased shear stress and mass transport, to potentially unwanted side effects such as temperature fluctuations. A thorough understanding of these properties and their implications on the culture model can aid with a more accurate interpretation of results. Improved and more complete characterisation of bioreactor properties will also lead to greater accuracy when reporting culture conditions in protocols, aiding experimental reproducibility, and allowing more precise comparison of results between different systems. In this review we provide an analysis of the different factors involved in the development of benchtop flow bioreactors and their potential biological impacts across a range of applications.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"8 ","pages":"Article 100063"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666534422000253/pdfft?md5=73f8311e4b6ecb201f3a917ccd86b791&pid=1-s2.0-S2666534422000253-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91728666","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":"Neural progenitor cell-derived extracellular matrix as a new platform for neural differentiation of human induced pluripotent stem cells","authors":"Marta S. Carvalho ,&nbsp;Diogo E.S. Nogueira ,&nbsp;Joaquim M.S. Cabral ,&nbsp;Carlos A.V. Rodrigues","doi":"10.1016/j.bbiosy.2022.100070","DOIUrl":"10.1016/j.bbiosy.2022.100070","url":null,"abstract":"<div><p>The culture microenvironment has been demonstrated to regulate stem cell fate and to be a crucial aspect for quality-controlled stem cell maintenance and differentiation to a specific lineage. In this context, extracellular matrix (ECM) proteins are particularly important to mediate the interactions between the cells and the culture substrate. Human induced pluripotent stem cells (hiPSCs) are usually cultured as anchorage-dependent cells and require adhesion to an ECM substrate to support their survival and proliferation <em>in vitro</em>. Matrigel, a common substrate for hiPSC culture is a complex and undefined mixture of ECM proteins which are expensive and not well suited to clinical application. Decellularized cell-derived ECM has been shown to be a promising alternative to the common protein coatings used in stem cell culture. However, very few studies have used this approach as a niche for neural differentiation of hiPSCs.</p><p>Here, we developed a new stem cell culture system based on decellularized cell-derived ECM from neural progenitor cells (NPCs) for expansion and neural differentiation of hiPSCs, as an alternative to Matrigel and poly-<span>l</span>-ornithine/laminin-coated well plates. Interestingly, hiPSCs were able to grow and maintain their pluripotency when cultured on decellularized ECM from NPCs (NPC ECM). Furthermore, NPC ECM enhanced the neural differentiation of hiPSCs compared to poly-<span>l</span>-ornithine/laminin-coated wells, which are used in most neural differentiation protocols, presenting a statistically significant enhancement of neural gene expression markers, such as <em>βIII-Tubulin and MAP2</em>.</p><p>Taken together, our results demonstrate that NPC ECM provides a functional microenvironment, mimicking the neural niche, which may have interesting future applications for the development of new strategies in neural stem cell research.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"8 ","pages":"Article 100070"},"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/a5/55/main.PMC9934470.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10762296","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":"A quest for cytocompatible metal organic frameworks in non-viral gene therapy: Relevance of zeolitic imidazolate framework-8","authors":"A. Poddar ,&nbsp;S. Pyreddy ,&nbsp;S.A. Polash ,&nbsp;C.M. Doherty ,&nbsp;R. Shukla","doi":"10.1016/j.bbiosy.2022.100065","DOIUrl":"10.1016/j.bbiosy.2022.100065","url":null,"abstract":"<div><p>Metal-organic frameworks (MOFs) are an emerging group of nanomaterials for successful biomedical applications in gene therapy. The most commonly biocompatible MOFs are zinc-based ZIFs, zirconium-based UiOs, and iron-based MILs. However, despite increasing applications, a comparative study to underscore the critical factors for determining effective gene delivery by such MOFs is lacking. Herein, we evaluate the potential of UiO-66 and MIL-88B and ZIF-8 for gene therapeutics delivery; revealing the comparative importance of ZIF-8. Cytotoxicity assays proved insufficient for selecting the ideal gene delivery MOF vehicle. Synthesis conditions such as ability of the MOF scaffold to envelop the gene during in-situ synthesis, post-treatment such as washing, and gene loading efficiency proved to be the critical factors in determining the favourable MOF from the material selection perspective. Rapid in-situ synthesis under physiological conditions, successful gene loading, and low concentration requirements favour ZIF MOFs as gene delivery vehicles. Impact on cellular physiology, metabolism, and architecture revealed neutrality of the delivery system; and relative effects on pro-inflammatory and anti-inflammatory cytokines suggest immunomodulatory impact.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"8 ","pages":"Article 100065"},"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/e7/dd/main.PMC9934432.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10762297","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":"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 ,&nbsp;Kassapa Ellepola ,&nbsp;Vitaly Sorokin ,&nbsp;Mario Ihsan ,&nbsp;Nikolaos Silikas ,&nbsp;AH Castro Neto ,&nbsp;Chaminda Jayampath Seneviratne ,&nbsp;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 &gt; 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}

{"title":"Contraction pressure analysis using optical imaging in normal and MYBPC3-mutated hiPSC-derived cardiomyocytes grown on matrices with tunable stiffness","authors":"Matthijs Snelders ,&nbsp;Iris H. Koedijk ,&nbsp;Julia Schirmer ,&nbsp;Otto Mulleners ,&nbsp;Juancito van Leeuwen ,&nbsp;Nathalie P. de Wagenaar ,&nbsp;Oscar Bartulos ,&nbsp;Pieter Voskamp ,&nbsp;Stefan Braam ,&nbsp;Zeno Guttenberg ,&nbsp;A.H. Jan Danser ,&nbsp;Danielle Majoor-Krakauer ,&nbsp;Erik Meijering ,&nbsp;Ingrid van der Pluijm ,&nbsp;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}

{"title":"Human endothelial cells form an endothelium in freestanding collagen hollow filaments fabricated by direct extrusion printing","authors":"Ina Prade ,&nbsp;Michaela Schröpfer ,&nbsp;Caroline Seidel ,&nbsp;Claudia Krumbiegel ,&nbsp;Tina Hille ,&nbsp;Frank Sonntag ,&nbsp;Stephen Behrens ,&nbsp;Florian Schmieder ,&nbsp;Birgit Voigt ,&nbsp;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}

{"title":"Use of polypyrrole-polystyrene membranes for extracting DNA from plant tissues","authors":"Winnie Q. Brandão ,&nbsp;Romário J. da Silva ,&nbsp;Lizeth C. Mojica-Sánchez ,&nbsp;Bruna G. Maciel ,&nbsp;Gabriela P. Ratkovski ,&nbsp;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}

{"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 ,&nbsp;Patrick Barton ,&nbsp;Reiner Class ,&nbsp;Hannah Coxhead ,&nbsp;Claude Delatour ,&nbsp;Eric Gillent ,&nbsp;Jamie Henshall ,&nbsp;Emre M. Isin ,&nbsp;Lloyd King ,&nbsp;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}