High throughput methods applied in biomaterial development and discovery

The high throughput discovery of new materials can be achieved by rapidly screening many different materials synthesised by a combinatorial approach to identify the optimal material that fulfils a particular biomedical application. Here we review the literature in this area and conclude that for polymers, this process is best achieved in a microarray format, which enable thousands of cell-material interactions to be monitored on a single chip. Polymer microarrays can be formed by printing pre-synthesised polymers or by printing monomers onto the chip where on-slide polymerisation is initiated. The surface properties of the material can be analysed and correlated to the biological performance using high throughput surface analysis, including time-of-flight secondary ion mass spectrometry (ToF-SIMS), X-ray photoelectron spectroscopy (XPS) and water contact angle (WCA) measurements. This approach enables the surface properties responsible for the success of a material to be understood, which in turn provides the foundations of future material design. The high throughput discovery of materials using polymer microarrays has been explored for many cell-based applications including the isolation of specific cells from heterogeneous populations, the attachment and differentiation of stem cells and the controlled transfection of cells. Further development of polymerisation techniques and high throughput biological assays amenable to the polymer microarray format will broaden the combinatorial space and biological phenomenon that polymer microarrays can explore, and increase their efficacy. This will, in turn, result in the discovery of optimised polymeric materials for many biomaterial applications

Cell spreading correlates with calculated logP of amino acid-modified surfaces

The interactions of cells with synthetic surfaces are a critical factor in biomaterials design and it would be invaluable if these interactions could be precisely controlled and predicted. Hydrophobicity or lipophilicity of the surface is commonly used to rationalize cell attachment to materials. In the pharmaceutical sciences it is common practice to use logP, the partitioning coefficient between water and octanol, as a reliable indicator of the hydrophobicity or lipophilicity of (drug) molecules. A number of methods are available to reliably predict logP values directly from molecular structure. In this paper we demonstrate that logP values calculated on the basis of the molecular structure of a range of surface-tethered groups correlate well with cell spreading. To our knowledge this is the first method to predict cell spreading on chemically modified surfaces via nonspecific interactions. © 2007 Acta Materialia Inc

Enzyme-activated RGD ligands on functionalized poly(ethylene glycol) monolayers: surface analysis and cellular response

We report on the design, stepwise synthesis, and surface analysis of enzyme-responsive surfaces that present cell adhesive RGD sequences on-demand, that is, by enzymatic hydrolysis of inactive RGD containing precursors that carry cleavable steric blocking groups. These surfaces, incorporating poly(ethylene glycol) (PEG) monolayers coupled via epoxy silanes to glass, are functionalized via stepwise solid phase synthesis, presenting a versatile and straightforward approach to preparation of peptide surfaces. Successive amino acid coupling and deprotection steps using fluorenylmethoxycarbonyl (Fmoc) chemistry are verified using surface analysis with time-of-flight secondary-ion mass spectrometry (ToF-SIMS) and X-ray photoelectron spectroscopy (XPS). Exposure of surfaces to elastase results in activation of cell binding ligands as demonstrated using osteoblast cells. These surfaces may have applications in spatiotemporally controlled attachment of cells as relevant for three-dimensional tissue engineering scaffolds and cell-based biosensors