A novel, three-dimensional (3-D) screening method for
analyzing interactions between cells and new biomaterials could cut
initial search times by more than half, researchers from the National
Institute of Standards and Technology (NIST) and Rutgers University
report in the new issue of Advanced Materials. The technique, an
advance over flat, two-dimensional screening methods, enables rapid
assessment of the biocompatibility and other properties of materials
designed for repairing—or even rebuilding—damaged
tissues and organs.
Confocal microscope images show how growth and adhesion of bone cells differ across a subset of 3-D scaffolds made with systematically varying blends of ingredients. Red indicates actin filaments, a cytoskeletal protein, and yellow indicates a cell nucleus
In what may be a first, the team demonstrated how to screen
cell–material interactions in a biologically representative,
but systematically altered, 3-D environment. The pivotal step in the
experiment was the collaborators’ success in making so-called
libraries of miniature porous scaffolds that are bone-like in structure
but vary incrementally in chemical composition. Knowing how changes in
scaffold ingredients influence cell responses, researchers can devise
strategies for developing biomaterials optimized for particular
therapies and treatments.
Until now, attempts to accelerate screening of candidate
biomaterials have used flat films and surfaces. (See, for example,
“Designer Gradients Speed Surface Science
Experiments,” Tech Beat June 8, 2006.
Along with other shortcomings, these two-dimensional substrates are
neither consistent with cells’ normal 3-D environment inside
the body nor with the most common intended use of biomaterials:
creating scaffolds to encourage the growth of cells into functional 3-D
tissues and organs.
“Cells are very sensitive to the texture, shapes,
and other three-dimensional features of their local environment inside
the body,” explains NIST biomaterial scientist Carl Simon.
“The large difference in structure between 2-D films and 3-D
scaffolds should be considered when screening new materials.”
On a series of plates, each about the size of a dollar bill
and arrayed with 96 scaffolds the size of pencil erasers, the
researchers conducted the equivalent of 672 individual tests. In all,
the tests yielded data for eight separate but related investigations,
each one using libraries of 36 incrementally varying scaffolds and 12
controls. On each plate, tests were performed concurrently.
The six cell-culture investigations and two studies of
scaffold structure were completed in six days, as compared with 24 days
for the traditional method of preparing and testing each sample
In the cell culture experiments, the team analyzed how
variations in the chemical makeup of the tiny scaffolds affected the
ability of bone-building cells called osteoblasts to multiply and to
adhere to scaffolds. The scaffold libraries were made by blending
varying proportions of two different compounds prepared at Rutgers
based on the amino acid tyrosine, which is a component of proteins
found in hair, skin, and other parts of the body.
The project yielded a unique data set, where two materials
have been tested side by side in both 2-D and 3-D. In this case,
results with 2-D films were predictive of the trends observed with 3-D
scaffolds. Further work is required to determine if this will hold true
for other cell-material systems.