COMBINATORIAL APPROACH TO BIOMATERIALS DESIGN

Project Details

Description

(Adapted from the applicant's abstract) This application is part of a
package of four individual R01 applications. The long-term goal of this
application is to develop a new paradigm for the optimization of the
design of porous polymeric scaffolds based on combinatorial approaches
to both polymer design and the exploration of cell-scaffold
interactions. The work plan is built around the hypothesis that the
interaction of cells with a polymeric scaffold is influenced by both
materials-related and architecture-related design parameters. To
explore the multifaceted interactions between cells and surfaces, four
distinct research aspects have been defined that will be addressed
concomitantly by a team of collaborators consisting of a polymer
scientist, a biomedical engineer, and a cell/molecular biologist.
Initially, a unique, combinatorial library of new polymers will be
created such that specific material properties can be varied in a
predictable and incremental fashion. Next, microscopically smooth, flat
surfaces will be used as a simple model architecture. Mouse L929
fibroblasts, human dermal fibroblasts, osteoblasts, and endothelial
cells will be used to examine the cellular responses in terms of
attachment, migration, growth, and differentiation. These observations
will be correlated to specific surface properties and the adsorption of
extracellular matrix (ECM) proteins. Employing poly(DTE adipate) as a
representative material, polymeric scaffolds will be fabricated using
a series of specific architectural designs. Finally, in an efficient
combinatorial scheme, both materials-and architecture-related design
parameters will be varied in specific scaffold configurations to examine
the cellular responses in 3-D culture conditions. The outcomes of this
research plan are threefold: (1) predictive, quantitative models will
be developed describing the correlations between material chemical
composition, protein adsorption, and cellular responses in 2- and 3-D
culture conditions, (2) the design of polymeric scaffolds with optimal
properties will be facilitated, and (3) the possible applications in
tissue engineering of the first combinatorial library of degradable
polymers will be evaluated. The associated research projects of
Professor Parsons (using the same library of polymers in hard tissue)
and Professor Edelman (using the same library of polymers in
cardiovascular applications) will provide the necessary extension of
this work to in vivo systems.
StatusFinished
Effective start/end date7/10/986/30/02

Funding

  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute: $195,000.00
  • National Heart, Lung, and Blood Institute: $195,000.00

ASJC

  • Polymers and Plastics
  • Cell Biology

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