Plant Flavonoid-Mediated Multifunctional Surface Modification Chemistry: Catechin Coating for Enhanced Osteogenesis of Human Stem Cells

Application of surface chemistry using bioactive compounds enables simple functionalization of tissue-engineering scaffolds for improved biocompatibility and regenerative efficacy. Recently, surface modifications using natural polyphenols have been reported to serve as efficient multifunctional coating; however, there has yet to be any comprehensive application in tissue engineering. Here, we report a simple, multifunctional surface modification using catechin, a phenolic compound with many biological functions, found primarily in plants, to potentiate the functionality of polymeric scaffolds for bone regeneration by stem cells. We found that catechin hydrate can be efficiently deposited on the surface of various substrates and can greatly increase hydrophilicity of the substrates. While identifying the chemical mechanisms regulating catechin surface coating, we found that catechin molecules can self-assemble into dimers via cation-pi interactions. Interestingly, the intrinsic biochemical functions of catechin coating provided the polymer scaffolds with antioxidative and calcium-binding abilities, resulting in enhanced adhesion, proliferation, mineralization, and osteogenic differentiation of human adipose-derived stem cells (hADSCs). Ultimately, catechin-functionalized polymer nanofiber scaffolds significantly promoted in vivo bone formation by hADSC transplantation in a critical-sized calvarial bone defect. Our study demonstrates that catechin can provide a biocompatible, multifunctional, and cost-effective surface modification chemistry to produce functional scaffolds with improved tissue regenerative efficacy.