Building biophysical and biochemical complexity in 3D cell and tissue constructs

在 3D 细胞和组织结构中构建生物物理和生化复杂性

• 批准号: 10701919
• 负责人: Christopher B Highley
• 金额: $ 37.35万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10701919
• 关键词: 3-Dimensional; Address; Adult; Applied Research; Behavior; Biochemical; Biocompatible Materials; Biological; Biology; Biomechanics; Biomimetics; Biophysics; Blood Vessels; Cell Communication; Cell Density; Cell model; Cell physiology; Cells; Clinical; Complex; Cues; Development; Disease; Disease Progression; Engineering; Environment; Goals; Hydrogels; In Vitro; Medical; Metabolic; Methods; Modification; Organ Transplantation; Organism; Patients; Phenotype; Population; Positioning Attribute; Process; Research; Resolution; Signal Transduction; Specific qualifier value; Stimulus; Structure; Supporting Cell; System; Technology; Therapeutic; Therapeutic Uses; Time; Tissue Engineering; Tissue Model; Tissue constructs; Tissues; Translational Research; Vascularization; Work; biofabrication; biological systems; bioprinting; design; experience; in vitro Model; in vivo; innovation; meetings; model building; replacement tissue; response; three dimensional structure; translational medicine; two-dimensional

Abstract Within healthy adult tissues, a developing organism, and disease environments alike, cells exist in environments where they receive and integrate external signals according to a phenotypic state, yielding responses in cellular activities and behaviors or modifications to phenotypic state. Fundamental understanding of cellular functioning and disease progression depends in part on our ability to systematically build and perturb model cellular systems in vitro, and pressing biomedical challenges in translational medicine might be addressed through the technology that enables breakthroughs in tissue engineering, including in meeting the critical needs of patients awaiting organ transplants. Over the past decades, a range of biofabrication technologies have been used to precisely arrange cells and materials within two- and three-dimensional structures. These technologies have broadened our understanding biology and increased the complexity of tissue constructs that might be used therapeutically. While biofabrication approaches developed over this time have greatly benefitted our abilities to probe and understand biological questions—especially with respect to cells and their environments—and to engineer cell-material constructs that recapitulate features of native tissues, significant challenges persist in building multiscale biomimetic tissue constructs. Our lab’s research is focused on addressing these challenges through the development and application of new biofabrication technologies that are based on innovation in the design and use of hydrogel biomaterials. Within the next five years, the lab aims to develop and apply unique hydrogel-based technology to bioprinting to address the critical need for capabilities to create vascularized tissue constructs in which cell and material complexity can be specified in extravascular regions and that can support dense cell populations. The lab will also develop new biofabrication technologies that will allow unique capabilities for high resolution control over cellular and material structures within macroscale constructs, with the goal of being able to simultaneously control a broad range of microenvironmental features—including cell-cell interactions, biochemical cues, and biomechanical cues—that a given cell experiences. We aim to develop technological capabilities and ultimately apply these capabilities to building complex tissue constructs that might be used as platforms for studying tissue and vascular responses to perturbations by physical and biological stimuli and to address key challenges in tissue engineering to develop therapeutic tissue constructs. The work in this proposal thus aims to advance capabilities in the fields of biofabrication and tissue engineering, with broad potential impacts in applied and translational research.

摘要