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Scholarly Works (4 results)

  • Thesis
  • Peer Reviewed
UC Riverside Electronic Theses and Dissertations (2017)

A lack of therapeutic technologies that enable electrically stimulating nervous tissues in a facile and clinically relevant manner has partly hindered the advancement in treating nerve injuries for full functional recovery. Currently, the gold standard for nerve repair is autologous nerve grafting. However, this method has several disadvantages, such as necessity for multiple surgeries, creation of functionally impaired region where graft was taken from, disproportion of graft to nerve tissue in size and structure, and most substantially, high risk of neuroma formation. Therefore, there is an increasing need for the development of alternative strategies to enhance nerve regeneration. To address these limitations, the development of a piezoelectric neuroconduit that can self-generate optimized levels of electrical stimulation can be utilized to wrap a damaged nerve and remotely activated by acoustically-driven piezoelectricity. Unlike biochemical-embedded conduit in which the release of neurotrophic factors is limited by loading or electro-conductive conduit in which only passive electrical stimulation by autologous cells is possible without intrusive electrodes, the piezoelectric conduit provides unlimited opportunity to properly stimulate the neuronal cells in vivo. In this regard, a piezoelectric scaffold was developed using electrospinning technology and its piezoelectric performance was optimized by controlling the fiber diameter and scaffold thickness. Various types of neural cells including PC12 cells, Schwann cells, and neural stem cells (NSCs), were subjected to mechanical/electrical stimulation to examine their behavioral changes. When PC12 cells, a model system for neurons, were subjected to multi-day application of mechanical/electrical stimulation, enhancements in neurite formation and elongation were observed. Alternatively, mechanical/electrical stimulation induced Schwan cells, the glial cell of the peripheral nervous system, to differentiate into its myelinating phenotype and induced the enhanced production of the neurotrophic protein, nerve growth factor. Aside from enhancing the functionality of neuronal and glial cells, mechanical/electrical stimulation also induced the differentiation of NSCs towards the functional cell types of the central nervous system, neurons, oligodendrocytes, and astrocytes. Therefore, this project develops a novel method for enhancing nerve regeneration by modulating neuron and glial cell functionality for the repair of nerve injuries.

    Cover page: Remote-Activated Electrical Stimulation via Piezoelectric Scaffold System for Functional Peripheral and Central Nerve RegenerationCreative Commons 'BY' version 4.0 license
    • Article
    • Peer Reviewed
    UC Riverside Previously Published Works (2018)
    Hydrogels have shown great potential for cartilage tissue engineering applications due to their capability to encapsulate cells within biomimetic, 3-dimensional (3D) microenvironments. However, the multi-step fabrication process that is necessary to produce cell/scaffold constructs with defined dimensions, limits their off-the-shelf translational usage. In this study, we have developed a hybrid scaffolding system which combines a thermosensitive hydrogel, poly(ethylene glycol)-poly(N-isopropylacrylamide) (PEG-PNIPAAm), with a biodegradable polymer, poly(ε-caprolactone) (PCL), into a composite, electrospun microfibrous structure. A judicious optimization of material composition and electrospinning process produced a structurally self-supporting hybrid scaffold. The reverse thermosensitivity of PEG-PNIPAAm allowed its dissolution/hydration upon cell seeding within a network of PCL microfibers while maintaining the overall scaffold shape at room temperature. A subsequent temperature elevation to 37 °C induced the hydrogel's phase transition to a gel state, effectively encapsulating cells in a 3D hydrogel without the use of a mold. We demonstrated that the hybrid scaffold enhanced chondrogenic differentiation of human mesenchymal stem cells (hMSCs) based on chondrocytic gene and protein expression, which resulted in superior viscoelastic properties of the cell/scaffold constructs. The hybrid scaffold enables a facile, single-step cell seeding process to inoculate cells within a 3D hydrogel with the potential for cartilage tissue engineering.

    Statement of significance

    Hydrogels have demonstrated the excellent ability to enhance chondrogenesis of stem cells due to their hydrated fibrous nanostructure providing a cellular environment similar to native cartilage. However, the necessity for multi-step processes, including mixing of hydrogel precursor with cells and subsequent gelation in a mold to form a defined shape, limits their off-the-shelf usage. In this study, we developed a hybrid scaffold by combining a thermosensitive hydrogel with a mechanically stable polymer, which provides a facile means to inoculate cells in a 3D hydrogel with a mold-less, single step cell seeding process. We further showed that the hybrid scaffold enhanced chondrogenesis of mesenchymal stem cells, demonstrating its potential for cartilage tissue engineering.
      Cover page: Electrospun thermosensitive hydrogel scaffold for enhanced chondrogenesis of human mesenchymal stem cells
      • Article
      • Peer Reviewed
      UC Riverside Previously Published Works (2017)
      Monitoring pluripotent stem cell behaviors (self-renewal and differentiation to specific lineages/phenotypes) is critical for a fundamental understanding of stem cell biology and their translational applications. In this study, a multi-modal stem cell monitoring system was developed to quantitatively characterize physico-electrochemical changes of the cells in real time, in relation to cellular activities during self-renewal or lineage-specific differentiation, in a non-destructive, label-free manner. The system was validated by measuring physical (mass) and electrochemical (impedance) changes in human induced pluripotent stem cells undergoing self-renewal, or subjected to mesendodermal or ectodermal differentiation, and correlating them to morphological (size, shape) and biochemical changes (gene/protein expression). An equivalent circuit model was used to further dissect the electrochemical (resistive and capacitive) contributions of distinctive cellular features. Overall, the combination of the physico-electrochemical measurements and electrical circuit modeling collectively offers a means to longitudinally quantify the states of stem cell self-renewal and differentiation.
        Cover page: Physico-electrochemical Characterization of Pluripotent Stem Cells during Self-Renewal or Differentiation by a Multi-modal Monitoring System
        • Article
        • Peer Reviewed
        UC Riverside Previously Published Works (2021)
        Due to dissimilarities in genetics and metabolism, current animal models cannot accurately depict human neurological diseases. To develop patient-specific in vitro neural models, a functional material-based technology that offers multi-potent stimuli for enhanced neural tissue development is devised. An electrospun piezoelectric poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) nanofibrous scaffold is systematically optimized to maximize its piezoelectric properties while accommodating the cellular behaviors of neural stem cells. Hydro-acoustic actuation is elegantly utilized to remotely activate the piezoelectric effect of P(VDF-TrFE) scaffolds in a physiologically-safe manner for the generation of cell-relevant electric potentials. This mechano-electrical stimulation, which arose from the deflection of the scaffold and its consequent generation of electric charges on the scaffold surface under hydro-acoustic actuation, induces the multi-phenotypic differentiation of neural stem cells simultaneously toward neuronal, oligodendrocytic, and astrocytic phenotypes. As compared to the traditional biochemically-mediated differentiation, the 3D neuron-glial interface induced by the mechano-electrical stimulation results in enhanced interactions among cellular components, leading to superior neural connectivity and functionality. These results demonstrate the potential of piezoelectric material-based technology for developing functional neural tissues in vitro via effective neural stem cell modulation with multi-faceted regenerative stimuli.
          Cover page: Formation of 3D Self‐Organized Neuron‐Glial Interface Derived from Neural Stem Cells via Mechano‐Electrical Stimulation
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