arXiv subjects

Richard J. McMurtrey

Publications and source records attributed to Richard J. McMurtrey.

5 recordsLinked to original sources

arXiv2017

Roles of Diffusion Dynamics and Molecular Concentration Gradients in Cellular Differentiation and Three-Dimensional Tissue Development

Recent advancements in the ability to construct three-dimensional (3D) tissues and organoids from stem cells and biomaterials have not only opened abundant new research avenues in disease modeling and regenerative medicine but also have ignited investigation into important aspects of molecular diffusion in 3D cellular architectures. This paper describes fundamental mechanics of diffusion with equations for modeling these dynamic processes under a variety of scenarios in 3D cellular tissue constructs. The effects of these diffusion processes and resultant concentration gradients are described in the context of the major molecular signaling pathways in stem cells that both mediate and are influenced by gas and nutrient concentrations, including how diffusion phenomena can affect stem cell state, cell differentiation, and metabolic states of the cell. The application of these diffusion models and pathways is of vital importance for future studies of developmental processes, disease modeling, and tissue regeneration.

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arXiv2016

Multi-Compartmental Biomaterial Scaffolds for Patterning Neural Tissue Organoids in Models of Neurodevelopment and Tissue Regeneration

Biomaterials are becoming an essential tool in the study and application of stem cell research. Various types of biomaterials enable three-dimensional (3D) culture of stem cells, and, more recently, also enable high-resolution patterning and organization of multicellular architectures. Biomaterials also hold potential to provide many additional advantages over cell transplants alone in regenerative medicine. This paper describes novel designs for functionalized biomaterial constructs that guide tissue development to targeted regional identities and structures. Such designs comprise compartmentalized regions in the biomaterial structure that are functionalized with molecular factors that form concentration gradients through the construct and guide stem cell development, axis patterning, and tissue architecture, including rostral/caudal, ventral/dorsal, or medial/lateral identities of the central nervous system. The ability to recapitulate innate developmental processes in a 3D environment and under specific controlled conditions has vital application to advanced models of neurodevelopment and for repair of specific sites of damaged or diseased neural tissue.

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arXiv2015

Analytic and Numerical Models of Oxygen and Nutrient Diffusion, Metabolism Dynamics, and Architecture Optimization in Three-Dimensional Tissue Constructs with Applications and Insights in Cerebral Organoids

Diffusion models are important in tissue engineering as they enable an understanding of molecular delivery to cells in tissue constructs. As three-dimensional (3D) tissue constructs become larger, more intricate, and more clinically applicable, it will be essential to understand internal dynamics and signaling molecule concentrations throughout the tissue. Diffusion characteristics present a significant limitation in many engineered tissues, particularly for avascular tissues and for cells whose viability, differentiation, or function are affected by concentrations of oxygen and nutrients. This paper seeks to provide novel analytic solutions for certain cases of steady-state and non-steady-state diffusion and metabolism in 3D construct designs (planar, cylindrical, and spherical forms), solutions that otherwise require mathematical approximations achieved through numerical methods. This model is applied to cerebral organoids, where it is shown that limitations in diffusion and organoid size can be partially overcome by localizing metabolically-active cells to an outer layer in a sphere, a regionalization process that is known to occur through neuroglial precursor migration both in organoids and in early brain development. The given prototypical solutions include a review of metabolic information for many cell types and can be broadly applied to many forms of tissue constructs. This work enables researchers to model oxygen and nutrient delivery to cells, predict cell viability, design constructs with improved diffusion capabilities, and accurately control molecular concentrations in tissue constructs that may be used in studying models of development and disease or for conditioning cells to enhance survival after insults like ischemia or implantation into the body, thereby providing a framework for better understanding and exploring the characteristics of engineered tissue constructs.

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arXiv2015

Novel Advancements in Three-Dimensional Neural Tissue Engineering and Regenerative Medicine

Neurological diseases and injuries present some of the greatest challenges in modern medicine, often causing irreversible and lifelong burdens in the people whom they afflict. These diagnoses have devastating consequences on millions of people each year, and yet there are currently no therapies or interventions that can repair the structure of neural circuits and restore neural tissue function in the brain and spinal cord. Despite the challenges of overcoming these limitations, there are many new approaches under development that hold much promise. Neural tissue engineering aims to restore and influence the function of damaged or diseased neural tissue generally through the use of stem cells and biomaterials. In this paper, several new 3D tissue constructs and designs are described for functional reconstruction of neural architecture. With the use of induced pluripotent stem cells or induced neuronal cells, these 3D constructs could then be studied as regional models of the central nervous system or could one day be implemented as autologous grafts into damaged sites of the nervous system in order to restore neural function, particularly for damaged sites of spinal cord, areas of stroke infarction, tumor resection sites, peripheral nerve injuries, or areas of neurodegeneration.

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arXiv2015

Patterned and Functionalized Nanofiber Scaffolds in Three-Dimensional Hydrogel Constructs Enhance Neurite Outgrowth and Directional Control

Neural tissue engineering holds incredible potential to restore functional capabilities to damaged neural tissue. It was hypothesized that patterned and functionalized nanofiber scaffolds could control neurite direction and enhance neurite outgrowth. Aligned nanofibers were created according to a mathematical model and were shown to enable significant control over the direction of neurite outgrowth in both two-dimensional (2D) and three-dimensional (3D) neuronal cultures. Laminin-functionalized nanofibers in 3D hyaluronic acid (HA) hydrogels enabled significant alignment of neurites with nanofibers, enabled significant neurite tracking of nanofibers, and significantly increased the distance over which neurites could extend. This work demonstrates the ability to create unique 3D neural tissue constructs using a combined system of hydrogel and nanofiber scaffolding. Importantly, patterned and biofunctionalized nanofiber scaffolds that can control direction and increase length of neurite outgrowth in three-dimensions hold much potential for neural tissue engineering. This approach offers advancements in the development of implantable neural tissue constructs that enable control of neural development and reproduction of neuroanatomical pathways, with the ultimate goal being the achievement of functional neural regeneration.

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