TY - JOUR
T1 - High-Throughput Assessment and Modeling of a Polymer Library Regulating Human Dental Pulp-Derived Stem Cell Behavior
AU - Rasi Ghaemi, Soraya
AU - Delalat, Bahman
AU - Gronthos, Stan
AU - Alexander, Morgan R.
AU - Winkler, David A.
AU - Hook, Andrew L.
AU - Voelcker, Nicolas H.
PY - 2018/11/14
Y1 - 2018/11/14
N2 - The identification of biomaterials that modulate cell responses is a crucial task for tissue engineering and cell therapy. The identification of novel materials is complicated by the immense number of synthesizable polymers and the time required for testing each material experimentally. In the current study, polymeric biomaterial-cell interactions were assessed rapidly using a microarray format. The attachment, proliferation, and differentiation of human dental pulp stem cells (hDPSCs) were investigated on 141 homopolymers and 400 diverse copolymers. The copolymer of isooctyl acrylate and 2-(methacryloyloxy)ethyl acetoacetate achieved the highest attachment and proliferation of hDPSC, whereas high cell attachment and differentiation of hDPSC were observed on the copolymer of isooctyl acrylate and trimethylolpropane ethoxylate triacrylate. Computational models were generated, relating polymer properties to cellular responses. These models could accurately predict cell behavior for up to 95% of materials within a test set. The models identified several functional groups as being important for supporting specific cell responses. In particular, oxygen-containing chemical moieties, including fragments from the acrylate/acrylamide backbone of the polymers, promoted cell attachment. Small hydrocarbon fragments originating from polymer pendant groups promoted cell proliferation and differentiation. These computational models constitute a key tool to direct the discovery of novel materials within the enormous chemical space available to researchers.
AB - The identification of biomaterials that modulate cell responses is a crucial task for tissue engineering and cell therapy. The identification of novel materials is complicated by the immense number of synthesizable polymers and the time required for testing each material experimentally. In the current study, polymeric biomaterial-cell interactions were assessed rapidly using a microarray format. The attachment, proliferation, and differentiation of human dental pulp stem cells (hDPSCs) were investigated on 141 homopolymers and 400 diverse copolymers. The copolymer of isooctyl acrylate and 2-(methacryloyloxy)ethyl acetoacetate achieved the highest attachment and proliferation of hDPSC, whereas high cell attachment and differentiation of hDPSC were observed on the copolymer of isooctyl acrylate and trimethylolpropane ethoxylate triacrylate. Computational models were generated, relating polymer properties to cellular responses. These models could accurately predict cell behavior for up to 95% of materials within a test set. The models identified several functional groups as being important for supporting specific cell responses. In particular, oxygen-containing chemical moieties, including fragments from the acrylate/acrylamide backbone of the polymers, promoted cell attachment. Small hydrocarbon fragments originating from polymer pendant groups promoted cell proliferation and differentiation. These computational models constitute a key tool to direct the discovery of novel materials within the enormous chemical space available to researchers.
KW - biomaterials
KW - high-throughput screening
KW - microarray
KW - quantitative structure-property relationships modelling
KW - regenerative medicine
UR - http://www.scopus.com/inward/record.url?scp=85056470858&partnerID=8YFLogxK
U2 - 10.1021/acsami.8b12473
DO - 10.1021/acsami.8b12473
M3 - Article
C2 - 30351898
AN - SCOPUS:85056470858
VL - 10
SP - 38739
EP - 38748
JO - ACS Applied Materials and Interfaces
JF - ACS Applied Materials and Interfaces
SN - 1944-8244
IS - 45
ER -