Successful cell culture on polymer substrates requires appropriate hydrophilicity, mechanical integrity, leaching stability, and non-toxicity; consequently, only a limited number of polymers meet these criteria. Meanwhile, processable substrates enable the fabrication of biomimetic environments and regulation of cellular growth and behavior. In this study, we fabricate a cell-permissive substrate by coating a hydrophobic covalent adaptable network (CAN)–based PDMS with collagen. The mechanical and chemical properties of the collagen-coated CAN PDMS confirm that the substrate provides a suitable environment for cell culture. Importantly, dynamic nature of the CAN substrate enables shape reconfiguration, allowing modulation of cell culture geometry. Furthermore, good processability of the CAN PDMS, enabled by dynamic bond-exchange reactions, is demonstrated. Overall, this approach enables a shape-reconfigurable polymer substrate with tunable cell culture characteristics.