skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Explore Research Products in the PAR
It may take a few hours for recently added research products to appear in PAR search results.


Title: Interfacing neural cells with typical microelectronics materials for future manufacturing
The biocompatibility of materials used in electronic devices is critical for the development of implantable devices like pacemakers and neuroprosthetics, as well as in future biomanufacturing. Biocompatibility refers to the ability of these materials to interact with living cells and tissues without causing an adverse response. Therefore, it is essential to evaluate the biocompatibility of metals and semiconductor materials used in electronic devices to ensure their safe use in medical applications. Here, we evaluated the biocompatibility of a collection of diced silicon chips coated with a variety of metal thin films, interfacing them with different cell types, including murine mastocytoma cells in suspension culture, adherent NIH 3T3 fibroblasts, and human induced pluripotent stem cell (iPSC)-derived neural progenitor cells (NPCs). All materials tested were biocompatible and showed the potential to support neural differentiation of iPSC-NPCs, creating an opportunity to use these materials in a scalable production of a range of biohybrid devices such as electronic devices to study neural behaviors and neuropathies.  more » « less
Award ID(s):
2426775
PAR ID:
10538957
Author(s) / Creator(s):
; ; ; ; ; ; ;
Publisher / Repository:
Elsevier
Date Published:
Journal Name:
Biosensors and Bioelectronics
Volume:
242
Issue:
C
ISSN:
0956-5663
Page Range / eLocation ID:
115749
Subject(s) / Keyword(s):
Biocompatibility Semiconductor materials Metal-cell interaction Pluripotent stem cells Neural cells Biomanufacturing
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. ; ; ; ; (, Advanced Science)
    Abstract Neural progenitor cells (NPCs) are a promising cell source to repair damaged nervous tissue. However, expansion of therapeutically relevant numbers of NPCs and their efficient differentiation into desired mature cell types remains a challenge. Material‐based strategies, including culture within 3D hydrogels, have the potential to overcome these current limitations. An ideal material would enable both NPC expansion and subsequent differentiation within a single platform. It has recently been demonstrated that cell‐mediated remodeling of 3D hydrogels is necessary to maintain the stem cell phenotype of NPCs during expansion, but the role of matrix remodeling on NPC differentiation and maturation remains unknown. By culturing NPCs within engineered protein hydrogels susceptible to degradation by NPC‐secreted proteases, it is identified that a critical amount of remodeling is necessary to enable NPC differentiation, even in highly degradable gels. Chemical induction of differentiation after sufficient remodeling time results in differentiation into astrocytes and neurotransmitter‐responsive neurons. Matrix remodeling modulates expression of the transcriptional co‐activator Yes‐associated protein, which drives expression of NPC stemness factors and maintains NPC differentiation capacity, in a cadherin‐dependent manner. Thus, cell‐remodelable hydrogels are an attractive platform to enable expansion of NPCs followed by differentiation of the cells into mature phenotypes for therapeutic use. 
    more » « less
  2. ; ; (, Genes)
    Autism spectrum disorder (ASD) is a neurodevelopmental disorder that impedes patients’ cognition, social, speech and communication skills. ASD is highly heterogeneous with a variety of etiologies and clinical manifestations. The prevalence rate of ASD increased steadily in recent years. Presently, molecular mechanisms underlying ASD occurrence and development remain to be elucidated. Here, we integrated multi-layer genomics data to investigate the transcriptome and pathway dysregulations in ASD development. The RNA sequencing (RNA-seq) expression profiles of induced pluripotent stem cells (iPSCs), neural progenitor cells (NPCs) and neuron cells from ASD and normal samples were compared in our study. We found that substantially more genes were differentially expressed in the NPCs than the iPSCs. Consistently, gene set variation analysis revealed that the activity of the known ASD pathways in NPCs and neural cells were significantly different from the iPSCs, suggesting that ASD occurred at the early stage of neural system development. We further constructed comprehensive brain- and neural-specific regulatory networks by incorporating transcription factor (TF) and gene interactions with long 5 non-coding RNA(lncRNA) and protein interactions. We then overlaid the transcriptomes of different cell types on the regulatory networks to infer the regulatory cascades. The variations of the regulatory cascades between ASD and normal samples uncovered a set of novel disease-associated genes and gene interactions, particularly highlighting the functional roles of ELF3 and the interaction between STAT1 and lncRNA ELF3-AS 1 in the disease development. These new findings extend our understanding of ASD and offer putative new therapeutic targets for further studies. 
    more » « less
  3. ; ; ; ; ; (, Advanced Healthcare Materials)
    Abstract Multielectrode arrays would benefit from intimate engagement with neural cells, but typical arrays do not present a physical environment that mimics that of neural tissues. It is hypothesized that a porous, conductive hydrogel scaffold with appropriate mechanical and conductive properties could support neural cells in 3D, while tunable electrical and mechanical properties could modulate the growth and differentiation of the cellular networks. By incorporating carbon nanomaterials into an alginate hydrogel matrix, and then freeze‐drying the formulations, scaffolds which mimic neural tissue properties are formed. Neural progenitor cells (NPCs) incorporated in the scaffolds form neurite networks which span the material in 3D and differentiate into astrocytes and myelinating oligodendrocytes. Viscoelastic and more conductive scaffolds produce more dense neurite networks, with an increased percentage of astrocytes and higher myelination. Application of exogenous electrical stimulation to the scaffolds increases the percentage of astrocytes and the supporting cells localize differently with the surrounding neurons. The tunable biomaterial scaffolds can support neural cocultures for over 12 weeks, and enable a physiologically mimicking in vitro platform to study the formation of neuronal networks. As these materials have sufficient electrical properties to be used as electrodes in implantable arrays, they may allow for the creation of biohybrid neural interfaces and living electrodes. 
    more » « less
  4. ; ; ; ; ; ; ; ; ; ; et al (, Nature Methods)
    Madhura Mukhopadhyay (Ed.)
    Hematopoietic humanized (hu) mice are powerful tools for modeling the function of the human immune system and are also widely used for preclinical and drug discovery studies. However, generating a functional human T cell compartment in hu mice remains challenging, primarily due to the species-related differences between human and mouse thymus. While engrafting human fetal thymic tissues can support robust T cell development in hu mice, tissue scarcity and ethical concerns limit their wide use. Here, we describe tissue engineered human thymus organoids generated from inducible pluripotent stem cells (iPSC-thymus) that can support the de novo generation of a diverse population of functional human T cells. T cells of iPSC-thymus engrafted hu mice could mediate both cellular and humoral immune responses, including mounting robust proinflammatory responses upon TCR engagement, inhibiting allogeneic tumor graft growth and facilitating efficient Ig class switching. Our findings suggest that hu mice engrafted with iPSC-thymus can work as a novel system to study the development and function of human T cells in vivo. 
    more » « less
  5. ; ; ; (, bioRxiv)
    null (Ed.)
    The human brain utilizes ~ 20% of all of the body’s metabolic resources, while chimpanzee brains use less than 10%. Although previous work shows significant differences in metabolic gene expression between the brains of primates, we have yet to fully resolve the contribution of distinct brain cell types. To investigate cell-type specific interspecies differences in brain gene expression, we conducted RNA-Seq on neural progenitor cells (NPCs), neurons, and astrocytes generated from induced pluripotent stem cells (iPSCs) from humans and chimpanzees. Interspecies differential expression (DE) analyses revealed that twice as many genes exhibit DE in astrocytes (12.2% of all genes expressed) than neurons (5.8%). Pathway enrichment analyses determined that astrocytes, rather than neurons, diverged in expression of glucose and lactate transmembrane transport, as well as pyruvate processing and oxidative phosphorylation. These findings suggest that astrocytes may have contributed significantly to the evolution of greater brain glucose metabolism with proximity to humans. 
    more » « less
  • Citation Formats
  • MLA
  • APA
  • Chicago
  • BibTeX
  • Save / Share this Record
  • Send to Email