High‐Density Polymer Microarrays: Identifying Synthetic Polymers that Control Human Embryonic Stem Cell Growth

Hansen, Anne; Mjoseng, Heidi K.; Zhang, Rong; Kalloudis, Michail; Koutsos, Vasileios; Sousa, Paul A. De; Bradley, Mark

doi:10.1002/adhm.201300489

Cited by 27 publications

(35 citation statements)

References 34 publications

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“…This is particularly relevant when large libraries of materials or material gradients are being assessed as these systems allow the response of a certain environment to large groups or populations of materials to be assessed, and hence provide a robust insight into underlying interactions . The polymer microarray format has become a key enabling tool for materials discovery and development, whereby hundreds to thousands of unique polymers are printed onto a single glass slide allowing for parallel screening. Further to the identification of novel materials, the large number of biological–material interactions that can be assessed using high‐throughput screening methodologies can be used to provide new insight into structure–function relationships.…”

Section: Introductionmentioning

confidence: 99%

ToF-SIMS analysis of a polymer microarray composed of poly(meth)acrylates with C₆derivative pendant groups

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2016

Surf. Interface Anal.

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Surface analysis plays a key role in understanding the function of materials, particularly in biological environments. Time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS) provides highly surface sensitive chemical information that can readily be acquired over large areas and has, thus, become an important surface analysis tool. However, the information‐rich nature of ToF‐SIMS complicates the interpretation and comparison of spectra, particularly in cases where multicomponent samples are being assessed. In this study, a method is presented to assess the chemical variance across 16 poly(meth)acrylates. Materials are selected to contain C6 pendant groups, and ten replicates of each are printed as a polymer microarray. SIMS spectra are acquired for each material with the most intense and unique ions assessed for each material to identify the predominant and distinctive fragmentation pathways within the materials studied. Differentiating acrylate/methacrylate pairs is readily achieved using secondary ions derived from both the polymer backbone and pendant groups. Principal component analysis (PCA) is performed on the SIMS spectra of the 16 polymers, whereby the resulting principal components are able to distinguish phenyl from benzyl groups, mono‐functional from multi‐functional monomers and acrylates from methacrylates. The principal components are applied to copolymer series to assess the predictive capabilities of the PCA. Beyond being able to predict the copolymer ratio, in some cases, the SIMS analysis is able to provide insight into the molecular sequence of a copolymer. The insight gained in this study will be beneficial for developing structure–function relationships based upon ToF‐SIMS data of polymer libraries. © 2016 The Authors Surface and Interface Analysis Published by John Wiley & Sons Ltd.

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Section: Introductionmentioning

confidence: 99%

ToF-SIMS analysis of a polymer microarray composed of poly(meth)acrylates with C₆derivative pendant groups

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Scurr

2016

Surf. Interface Anal.

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“…High throughput screening (HTS) strategies for biomaterials development have proved successful in identifying substrates capable of supporting clinically relevant cell types including hESCs [ 10 – 13 ], pancreatic islet cells [ 14 ] and hepatocytes [ 15 ]. The current study has employed a parallel screening approach to investigate the influence of a range of (meth)acrylate and (meth)acrylamide polymers on hESC-CM adhesion and functionality.…”

Section: Introductionmentioning

confidence: 99%

A defined synthetic substrate for serum-free culture of human stem cell derived cardiomyocytes with improved functional maturity identified using combinatorial materials microarrays

et al. 2015

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Cardiomyocytes from human stem cells have applications in regenerative medicine and can provide models for heart disease and toxicity screening. Soluble components of the culture system such as growth factors within serum and insoluble components such as the substrate on which cells adhere to are important variables controlling the biological activity of cells. Using a combinatorial materials approach we develop a synthetic, chemically defined cellular niche for the support of functional cardiomyocytes derived from human embryonic stem cells (hESC-CMs) in a serum-free fully defined culture system. Almost 700 polymers were synthesized and evaluated for their utility as growth substrates. From this group, 20 polymers were identified that supported cardiomyocyte adhesion and spreading. The most promising 3 polymers were scaled up for extended culture of hESC-CMs for 15 days and were characterized using patch clamp electrophysiology and myofibril analysis to find that functional and structural phenotype was maintained on these synthetic substrates without the need for coating with extracellular matrix protein. In addition, we found that hESC-CMs cultured on a co-polymer of isobornyl methacrylate and tert-butylamino-ethyl methacrylate exhibited significantly longer sarcomeres relative to gelatin control. The potential utility of increased structural integrity was demonstrated in an in vitro toxicity assay that found an increase in detection sensitivity of myofibril disruption by the anti-cancer drug doxorubicin at a concentration of 0.05 µM in cardiomyocytes cultured on the co-polymer compared to 0.5 µM on gelatin. The chemical moieties identified in this large-scale screen provide chemically defined conditions for the culture and manipulation of hESC-CMs, as well as a framework for the rational design of superior biomaterials.

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“…Arrays of polymers have been used by several groups as a high-throughput means to develop polymer-based matrices that support the self-renewal, proliferation, and differentiation of a variety of stem cell types (Brafman et al, 2010;Anderson et al, 2004;Hansen et al, 2014). Moreover, such technologies have been successfully used to identify specific biomaterial properties that precisely direct stem cell fate (Mei et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

A chemically defined substrate for the expansion and neuronal differentiation of human pluripotent stem cell-derived neural progenitor cells

et al. 2015

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Due to the limitation of current pharmacological therapeutic strategies, stem cell therapies have emerged as a viable option for treating many incurable neurological disorders. Specifically, human pluripotent stem cell (hPSC)-derived neural progenitor cells (hNPCs), a multipotent cell population that is capable of near indefinite expansion and subsequent differentiation into the various cell types that comprise the central nervous system (CNS), could provide an unlimited source of cells for such cell-based therapies. However the clinical application of these cells will require (i) defined, xeno-free conditions for their expansion and neuronal differentiation and (ii) scalable culture systems that enable their expansion and neuronal differentiation in numbers sufficient for regenerative medicine and drug screening purposes. Current extracellular matrix protein (ECMP)-based substrates for the culture of hNPCs are expensive, difficult to isolate, subject to batch-to-batch variations, and, therefore, unsuitable for clinical application of hNPCs. Using a high-throughput array-based screening approach, we identified a synthetic polymer, poly(4-vinyl phenol) (P4VP), that supported the long-term proliferation and self-renewal of hNPCs. The hNPCs cultured on P4VP maintained their characteristic morphology, expressed high levels of markers of multipotency, and retained their ability to differentiate into neurons. Such chemically defined substrates will eliminate critical roadblocks for the utilization of hNPCs for human neural regenerative repair, disease modeling, and drug discovery.

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High‐Density Polymer Microarrays: Identifying Synthetic Polymers that Control Human Embryonic Stem Cell Growth

Cited by 27 publications

References 34 publications

ToF-SIMS analysis of a polymer microarray composed of poly(meth)acrylates with C₆derivative pendant groups

ToF-SIMS analysis of a polymer microarray composed of poly(meth)acrylates with C₆derivative pendant groups

A defined synthetic substrate for serum-free culture of human stem cell derived cardiomyocytes with improved functional maturity identified using combinatorial materials microarrays

A chemically defined substrate for the expansion and neuronal differentiation of human pluripotent stem cell-derived neural progenitor cells

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High‐Density Polymer Microarrays: Identifying Synthetic Polymers that Control Human Embryonic Stem Cell Growth

Cited by 27 publications

References 34 publications

ToF-SIMS analysis of a polymer microarray composed of poly(meth)acrylates with C6derivative pendant groups

ToF-SIMS analysis of a polymer microarray composed of poly(meth)acrylates with C6derivative pendant groups

A defined synthetic substrate for serum-free culture of human stem cell derived cardiomyocytes with improved functional maturity identified using combinatorial materials microarrays

A chemically defined substrate for the expansion and neuronal differentiation of human pluripotent stem cell-derived neural progenitor cells

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ToF-SIMS analysis of a polymer microarray composed of poly(meth)acrylates with C₆derivative pendant groups

ToF-SIMS analysis of a polymer microarray composed of poly(meth)acrylates with C₆derivative pendant groups