Three-Dimensional Scaffolds for Bone Marrow Tissue Constructs

用于骨髓组织构建的三维支架

• 批准号: 7671614
• 负责人: Nicholas Alexander Kotov
• 金额: $ 17.63万
• 依托单位: NICO TECHNOLOGIES CORPORATION
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7671614
• 关键词: AIDS/HIV problem; Adhesives; Animals; Antineoplastic Agents; Antiviral Agents; Arthritis; Autoimmune Diseases; Biological; Biological Assay; Biological Models; Biological Sciences; Biotechnology; Bone Marrow; Bone Matrix; CXCL12 gene; Caliber; Capital; Cell Adhesion; Cell Communication; Cell Culture Techniques; Cell physiology; Cells; Ceramics; Characteristics; Charge; Chemical Structure; Clinical; Collaborations; Collagen; Complex; Cultured Cells; Data; Development; Diffusion; Dimensions; Drug Costs; Drug Evaluation; Drug Formulations; Drug Industry; Electron Microscope; Elements; Employee Strikes; Engineering; Environment; Equilibrium; Evaluation; Failure; Figs - dietary; Foundations; Fred Hutchinson Cancer Research Center; Goals; HIV; Hematopoietic; Hematopoietic Neoplasms; Hematopoietic stem cells; Human; Hydrogels; Image; In Vitro; Indium; Individual; Joints; Lead; Learning; Manufacturer Name; Medical; Methods; Michigan; Modeling; Monitor; Nutrient; Optics; Organ; Osteoblasts; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Preclinical Testing; Preparation; Procedures; Process; Production; Property; Protocols documentation; Reproducibility; Research; Research Personnel; Scanning; Signaling Protein; Small Business Technology Transfer Research; Staging; Stem cells; Stromal Cells; Surface; System; Technology; Testing; Texas; Time; Tissue Model; Tissues; Toxic effect; Universities; Vaccines; Work; absorption; analog; base; cancer type; computerized data processing; cost; cytokine; design; drug candidate; drug development; drug discovery; drug testing; improved; in vitro testing; light scattering; manufacturing process; matrigel; member; nanostructured; notch protein; novel; physical property; preclinical study; public health relevance; research and development; research study; response; scaffold; self-renewal; success; three-dimensional modeling; tool; two-dimensional; user-friendly

DESCRIPTION (provided by applicant): The overall R&D cycle for drugs costs $300-800 million in capital and up to 10-12 years in time. One of the reasons for such great cost is that the vast majority of drug candidates are screened out at the stages of animal and human trials. More efficient methods of testing of drugs at the stage of ex-vivo studies, which are substantially less expensive than animal and human testing cycles, will lead to improvement of the success rate of preclinical trials, accelerate on of drug discovery, reduction of the cost of pharmaceutical development, and better drugs. Efficacy of in-vitro testing can be significantly increased provided that better ex-vivo models for different organs and tissues are developed. In this Phase I STTR project involving a start-up company Nico Technology Corporation (NTCorp), University of Michigan, University of Texas Medical Branch, and Fred Hutchinson Cancer Research Center we propose the development of a new type of 3D scaffold that can (1) rectify the problems of existing 3D matrixes and (2) provide the pharmaceutical industry the possibility to develop convenient and reliable protocols for drug assessment in organ replicas, and in particular ex-vivo bone marrow construct. Phase I of the project is aimed at the proof-of-concept demonstration that 3D scaffolds based on inverted colloidal crystal (ICC) scaffolds with remarkable resemblance of its 3D topology to that of bone marrow can be produced. They will be made from hydrogel and enable surface marker assays traditionally used in drug testing. Specific Aims (SA) for the project. SA1: Manufacturing of Cell-Adhesive ICC Scaffolds from Hydrogel; SA2: Evaluation of Stem cell Replication Functionality in a Bone Marrow Replica from ICC Scaffolds. In perspective, the bone marrow replica can be a convenient model system for the use in anticancer and antiviral drugs as kits and assays both for academic and industrial researchers. This model has no current analogs and can significantly improve the traditional 2D cell culture discovery tools with a potential to reduce the drug failures at animal and human trials stages. PUBLIC HEALTH RELEVANCE: Evaluation of drugs can be significantly accelerated by testing them in tissue analogs, which require a suitable 3D matrix that affords engineering of different tissues and optical monitoring of the cellular processes in it. In this project we propose manufacturing of transparent 3D hydrogel scaffolds with inverted colloidal crystal (ICC) geometry. Commercial production of ICC scaffolds will provide drug manufacturers with a standardized, reliable, reproducible, user- friendly 3D matrix that can be used in a variety of ex-vivo drug testing procedures that has a potential to reduce the cost and shorten the time of drug development.

描述（由申请人提供）：药物的整体研发周期的资本为300-8亿美元，最多时间为10 - 12年。如此巨大的成本的原因之一是，在动物和人类试验的阶段将绝大多数候选者筛选出来。在前体研究阶段测试药物的更有效的方法，这些方法比动物和人类测试周期便宜得多，这将导致临床前试验的成功率提高，加速药物发现，降低药物发育成本以及更好的药物。只要开发出更好的器官和组织的外部模型，就可以显着提高体外测试的功效。在这阶段，I涉及一家初创公司Nico Technology Corporation（NTCORP），密歇根大学，德克萨斯大学医学分支和Fred Hutchinson Cancer Research Center的STTR项目，我们建议开发一种新型的3D支架，可以（1）纠正现有的3D Matrix和（2）的问题，以纠正现有的3D Matrix和（2）的问题，并提供了毒品，并提供了可靠性，并提供了可靠性，并提供了可靠性，并提供了可靠性，并提供了可靠性，并提供了可靠性的，并提供了可靠性，并提供了可靠性，并提供了可靠性的范围。前体骨髓构建体。该项目的第一阶段是针对概念验证的证明，即基于倒置的胶体晶体（ICC）支架的3D支架，其3D拓扑与骨髓的3D拓扑非常相似。它们将由水凝胶制成，并启用传统用于药物测试的表面标记测定。该项目的具体目标（SA）。 SA1：从水凝胶中制造细胞粘附ICC支架； SA2：评估来自ICC支架的骨髓复制品中的干细胞复制功能。从角度来看，骨髓复制品可以是一种方便的模型系统，用于用于抗癌和抗病毒药物作为学术和工业研究人员的套件和测定。该模型没有当前的类似物，可以显着改善传统的2D细胞培养发现工具，并有可能减少动物和人类试验阶段的药物失败。公共卫生相关性：通过在组织类似物中测试药物的评估可以显着加速，这需要合适的3D矩阵，该基质提供不同组织的工程以及对其中细胞过程的光学监测。在这个项目中，我们建议用倒置的胶体晶体（ICC）几何形状制造透明的3D水凝胶支架。 ICC脚手架的商业生产将为药物制造商提供标准化，可靠，可重复的，用户友好的3D矩阵，可用于各种前体药物测试程序，该程序有可能降低成本并缩短药物开发时间。