Rapid Bioorthogonal Chemistry Enables in Situ Modulation of the Stem Cell Behavior in 3D without External Triggers

ACS Applied Materials & Interfaces
Ying HaoXinqiao Jia

Abstract

Chemical modification of engineered microenvironments surrounding living cells represents a means for directing cellular behaviors through cell-matrix interactions. Presented here is a temporally controlled method for modulating the properties of biomimetic, synthetic extracellular matrices (ECM) during live cell culture employing the rapid, bioorthogonal tetrazine ligation with trans-cyclooctene (TCO) dienophiles. This approach is diffusion-controlled, cytocompatible, and does not rely on light, catalysts, or other external triggers. Human bone-marrow-derived mesenchymal stem cells (hMSCs) were initially entrapped in a hydrogel prepared using hyaluronic acid carrying sulfhydryl groups (HA-SH) and a hydrophilic polymer bearing both acrylate and tetrazine groups (POM-AT). Inclusion of a matrix metalloprotease (MMP)-degradable peptidic cross-linker enabled hMSC-mediated remodeling of the synthetic environment. The resultant network displayed dangling tetrazine groups for subsequent conjugation with TCO derivatives. Two days later, the stiffness of the matrix was increased by adding chemically modified HA carrying multiple copies of TCO (HA-TCO) to the hMSC growth media surrounding the cell-laden gel construct. In response, cells ...Continue Reading

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Citations

Jul 22, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Matthew R ArkenbergChien-Chi Lin
Jun 10, 2020·Macromolecular Rapid Communications·Samantha E HoltDaniel L Alge
Sep 15, 2020·Advanced Biosystems·Matthew R ArkenbergChien-Chi Lin

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