ELECTROSPUN COLLAGEN SCAFFOLDS FOR 3D CELLULAR MODELS FOR ANTI-NEOPLASTIC AGENTS

用于抗肿瘤药物 3D 细胞模型的电纺胶原蛋白支架

• 批准号: 7960178
• 负责人: MARY C FARACH-CARSON
• 金额: $ 5.46万
• 依托单位: UNIVERSITY OF DELAWARE
• 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 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7960178
• 关键词: 3-Dimensional; Affinity; Antineoplastic Agents; Basement membrane; Binding; Biocompatible Coated Materials; Biology; Breast; Caliber; Cell Line; Cell model; Cell surface; Cells; Chemicals; Collagen; Collagen Type I; Computer Retrieval of Information on Scientific Projects Database; Custom; Delaware; Development; Dimensions; Engineering; Environment; Epithelial Cells; Exhibits; Extracellular Matrix; Feasibility Studies; Fiber; Funding; Goals; Grant; Growth Factor; Human; Institution; Internet; Laboratories; Life; Malignant Neoplasms; Membrane Proteins; Modeling; Normal Cell; Physical environment; Plastics; Polymers; Process; Property; Prostate; Proteins; Recombinants; Research; Research Personnel; Resources; Science; Solutions; Source; Spiders; Stimulus; Surface; Technology; Testing; Textiles; Tissues; United States National Institutes of Health; Ursidae Family; Work; base; cancer cell; cell transformation; human tissue; nanofiber; nanoscale; neoplastic; poly(lactic acid); scaffold; small molecule; three dimensional structure; tissue culture; tumor; tumor growth

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Mary C. Farach-Carson Electrospun Collagen Scaffolds for Development of 3-D Cellular Models for Testing Anti-Neoplastic Agents Greater than 90% of cancers, including those from breast and prostate, originate from epithelial cells that line the surfaces of human tissues. This reflects the fact that these surface cells bear the brunt of exposure of living cells to environmental insult including physical and chemical stimuli. As these cells are transformed from normal cells to cancer cells, their properties change. Tumors form from cells that are released from their natural lining (or basement membrane) and form 3-D structures that interact with each other and with the microenvironment of the tissue around the tumor. Cancer cells growing flat on plastic tissue culture as single layers do not reflect many of the properties of whole tumors. This shortcoming limits their ability to serve as perfect models for testing of pharmacologically active compounds, including those that are being tested as anti-cancer drugs (anti-neoplastics). We propose to combine two technologies that have been optimized in our separate laboratories in Biology (BIO) and Materials Science and Engineering (MSE) to create new 3-D cellular materials possessing properties more similar to those in native tissues surrounding cancers. The goal of this work is to produce an electrospun micro- and nanofibrous scaffold that will support tumor growth in three dimensions. Electrospinning, an offshoot of electrospraying, will be used to spin spider web type fibers on which cells will be grown for characterization and testing of anti-cancer compounds. The fibers produced during the electrospinning process are nanoscale, with diameters ranging from 40 to 2000 nm compared to traditional textile fibers that have diameters of 5-200 ¿m. The primary advantage of electrospinning is that it uses tiny quantities (50-100 mg  the quantity that might result from a custom synthesis) of polymer in solution to form micro- and nanofibers. A second advantage is that additional components, e.g., small molecules, a second polymer, or cell binding factors can be added to the polymer solution and often be incorporated into the fiber during the electrospinning process. For a feasibility study, collagen (type I) was chosen as the matrix material because it is a major constituent of natural fibers and thus can structurally mimic the physical environment of the natural extracellular matrix (ECM). Collagen alone has been shown to promote cellular recognition and exhibits a high affinity for proteins like those found in cell surface binding and growth factors. We plan to coat the collagen based scaffolds with small recombinant fragments of the ECM basement membrane proteins which we have shown to be a useful protein coating material on polylactic acid (PLA) scaffolds. We believe this coating will provide a more natural environment to cancer cells such that they will grow more similarly to human tumors. As such, it will provide a superior way to test how cancer cells respond to pharmacologically active compounds and will provide a superior model for testing potential new anti-cancer drugs in 3-D culture.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 玛丽·C·法拉赫-卡森 用于开发用于测试抗肿瘤药物的 3D 细胞模型的静电纺丝胶原支架 超过 90% 的癌症，包括乳腺癌和前列腺癌，起源于人体组织表面的上皮细胞。这反映了这样一个事实：这些表面细胞在活细胞暴露于环境损害（包括物理和化学刺激）时首当其冲。当这些细胞从正常细胞转变为癌细胞时，它们的特性会发生变化。肿瘤由从其天然衬里（或基底膜）释放的细胞形成，并形成彼此相互作用并与肿瘤周围组织的微环境相互作用的 3D 结构。癌细胞在塑料组织培养物上以单层形式平坦生长并不能反映整个肿瘤的许多特性。这一缺点限制了它们作为测试药理学活性化合物的完美模型的能力，包括那些正在作为抗癌药物（抗肿瘤）进行测试的化合物。我们建议将生物学 (BIO) 和材料科学与工程 (MSE) 各自实验室优化的两项技术结合起来，创造出新的 3D 细胞材料，其特性与癌症周围的天然组织更相似。这项工作的目标是生产一种静电纺丝微米和纳米纤维支架，以支持肿瘤在三个维度上的生长。静电纺丝是电喷雾的一个分支，将用于纺丝蜘蛛网型纤维，细胞将在其上生长，以表征和测试抗癌化合物。静电纺丝过程中产生的纤维是纳米级的，直径范围为 40 至 2000 nm，而传统纺织纤维的直径为 5-200 µm。 静电纺丝的主要优点是它在溶液中使用微量（50-100 毫克，可能来自定制合成的数量）聚合物来形成微米纤维和纳米纤维。 第二个优点是可以将附加成分（例如小分子、第二聚合物或细胞结合因子）添加到聚合物溶液中，并且通常在静电纺丝过程中将其掺入纤维中。在可行性研究中，选择胶原蛋白（I 型）作为基质材料，因为它是天然纤维的主要成分，因此可以在结构上模拟天然细胞外基质 (ECM) 的物理环境。 单独的胶原蛋白已被证明可以促进细胞识别，并对蛋白质（如细胞表面结合和生长因子中发现的蛋白质）表现出高亲和力。我们计划用 ECM 基底膜蛋白的小重组片段涂覆基于胶原蛋白的支架，我们已证明这是聚乳酸 (PLA) 支架上有用的蛋白质涂层材料。我们相信这种涂层将为癌细胞提供更自然的环境，使它们的生长与人类肿瘤更加相似。因此，它将提供一种更好的方法来测试癌细胞如何对药理活性化合物做出反应，并为在 3D 培养中测试潜在的新型抗癌药物提供一个更好的模型。