Accurate predictions of cellular response using QSPR: a feasibility test of rational design of polymeric biomaterials

Abstract

We present a Surrogate (semi-empirical) model for prediction of cellular response to the surfaces of biodegradable polymers that have been designed for tissue engineering applications. The predictions of our model, when tested against experimental results, show a high degree of accuracy that is sufficient for rational design of polymeric materials for biomedical applications. The model was determined by fitting experimental data for a series of 62 polyarylates to a small number of polymer structure-based 'molecular descriptors' using the technique of partial least squares (PLS) regression. While PLS is commonly applied in quantitative structure activity relationship (QSAR) analysis employed in the pharmaceutical industry, this study marks the first time the technique has been extended to the problem of biomaterials discovery/design. Quantitative predictions of cellular response to six polymers (untested prior to model building) concurred with experiment within 15.8% on average. This performance compares quite favorably with the overall variation in experimental values for the library of polyarylates. Examination of the PLS 'loadings' reveals those structure-based features most associated with variations in the polymer performance properties, thereby providing direct guidance to the synthetic chemist in biomaterials design. q

Computational Methods for the Development of Polymeric Biomaterials

“…They fitted experimental data for a series of 62 polyarylates to a small number of molecular descriptors to predict cellular response to the surfaces of biodegradable polymers. [85] The authors per- [52] . Fig.…”

Combinatorial and High‐Throughput Methods in Macromolecular Materials Research and Development

“…Coupling the experimental results with computer modeling techniques allowed for the development of predictive quantitative structureproperty relationships for these materials. [116][117][118][119][120][121] An active area of research in polymer science is the use of biodegradable polymers to deliver therapeutic agents. Poly(b-amino esters) have potential as biodegradable drug delivery polymers and are easily synthesized by the conjugate addition of amines and acrylates.…”

“…[116][117][118][119] A model using three-dimensional molecular descriptors for the polymer molecular structure demonstrated good predictive capability. [171] Predictive models such as this can be used to direct future experiments and identify promising compositions that may have not been synthesized in the initial experiments.…”

Biomaterials Informatics

“…Taken together, these results provide useful clues for the rational design of polymers whose structural features lend themselves to optimal biological and materials properties. [80]. Fetal rat lung fi broblast (FRLF) proliferation was measured for 62 polymers using a commercially available MTS colormetric assay [18].…”