Cell adhesion is essential for achieving tissue regeneration and repair. Although cell adhesion proteins and peptides, such as RGD peptides, have been widely used to promote cell adhesion, their application is often hindered by challenges related to large-scale preparation and high costs. To overcome these challenges, we designed and synthesized RGD-mimicking random copolymers that can be synthesized from rapid and controllable NCA polymerization on a large scale. The optimal random copolymer promotes cellular behaviors such as cell adhesion, proliferation and migration, as well as the performance of RGD in a variety of cell types. Mechanistic studies revealed that the RGD-mimicking polymer showed strong binding affinity to αvβ3 integrin, in a manner analogous to RGD peptides. Our study suggests that ternary random copolymers can be potent candidates to mimic the RGD peptides and promote cell adhesion, providing a promising strategy to promote cell adhesion and tissue regeneration.
