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

这个子项目是众多研究子项目之一

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.