Integration of Combinatorial Synthesis, Rapid Screening, and Computational Modeling in Biomaterials Development

Jack R. Smith, Agnieszka Seyda, Norbert Weber, Doyle Knight, Sascha Abramson, Joachim Kohn

Research output: Contribution to journalReview articlepeer-review

60 Scopus citations


The advent of high-throughput combinatorial synthesis techniques in drug discovery has stimulated efforts to apply these techniques to the discovery of biomaterials. To be of practical utility, combinatorial approaches to biomaterials design require (i) the availability of parallel synthesis techniques to generate libraries of polymers, (ii) efficient assays for the rapid characterization of biorelevant material properties, and (iii) computational methods to efficiently model different biological responses in the presence of polymers. Here we report the integration of these methodologies and illustrate the potential of this approach to accelerate the development of new biomaterials. The parallel synthesis of a library of 112 biodegradable polyarylates has been reported previously. This library was used to develop efficient screening techniques to determine biorelevant polymer properties (fibrinogen adsorption, gene expression in macrophages, growth of fetal rat lung fibroblasts (RLFs)). A Surrogate (semiempirical) Model was developed (i) to determine molecular-scale polymer properties that correlate to various biological responses, and (ii) to predict fibrinogen adsorption and RLF growth on polymeric surfaces. For 38 out of 45 polymers, the model predicted the amount of fibrinogen adsorbed correctly within the error of the experimental measurements. The growth of rat lung fibroblasts was correctly predicted by the model for 41 out of 48 polymers. The correlation factor between the model's predicted values and the experimentally determined data was 0.54 ± 0.09 and 0.69 ± 0.12 for fibrinogen adsorption and RLF growth, respectively. The results presented here demonstrate the utility of combinatorial and computational approaches for the rational design of polymers for biomedical applications.

Original languageEnglish (US)
Pages (from-to)127-140
Number of pages14
JournalMacromolecular Rapid Communications
Issue number1
StatePublished - Jan 2 2004

All Science Journal Classification (ASJC) codes

  • Organic Chemistry
  • Polymers and Plastics
  • Materials Chemistry


  • Biocompatibility
  • Biodegradable
  • Biological applications of polymers
  • Computer modeling
  • Proteins

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