Murugan Ramalingam1,2, Marian F. Young2 and Carl G. Simon, Jr.1

1Polymers Division, National Institute of Standards and Technology, Gaithersburg, MD

2National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA


Functional tissue engineering is a rapidly emerging multi-disciplinary field that holds great potential for healthcare in addressing the gap between need and availability of donor tissues and organs.  Despite significant global research investment, few successful tissue engineering products have come to market, which shows that further acceleration in the research strategy of tissue engineering is required for its rapid and continued success.  Since combinatorial methods can accelerate research, we are developing a nanofiber scaffold-based combinatorial platform for screening the effect of tissue scaffolds on cell response.  Although previous approaches for high-throughput cell screening have used material libraries in the form of 2D surfaces, biomaterials are commonly used in a 3D format and cells behave more physiologically when cultured in 3D. 


Therefore, we report a new electrospinning technique for the production of well-defined 3D nanofiber scaffold libraries containing a continuous gradient in properties suitable for studying cell response. The libraries enable screening of many nanofiber scaffold compositions with a single scaffold specimen. In order to characterize the gradient nanofiber approach, dyes were incorporated into the polymer solutions used for electrospinning such that gradients in dyes were electrospun.  Dye absorbance was measured with a spectrophotometer to characterize composition quantitatively.  Next, nanofiber libraries with a gradient in hydroxyapatite nanoparticles (nHA) were fabricated so that the effect of nHA composition could be screened.  nHA was chosen because it is known to enhance osteoblast differentiation and osteogenesis.  Thermogravimetric analysis was used to demonstrate that the nanofiber mats contained gradients in nHA composition.  Initial studies on human stem cell culture show that the combinatorial approach based on gradient scaffold libraries could be utilized for rapid screening of cellular response to the nanoscale materials, which could eventually accelerate the tissue engineering research.