Intracellular pH-responsive iron–catechin nanoparticles with osteogenic/anti-adipogenic and immunomodulatory effects for efficient bone repair

Osteoimmunomodulation was identified as a new and important strategy to enhance osteogenic differentiation together with other osteogenic approaches. However, approaches regulating osteogenic differentiation and macrophage polarization to remodel an osteoinductive microenvironment are separate and complicated. Therefore, the design and synthesis of one biomaterial that couples the osteogenic performance and immunomodulatory ability is a major challenge for efficient bone repair. In this study, self-assembled iron–catechin nanoparticles (Fe–cat NPs) were designed based on the coordinated reaction between iron ions and catechin and synthesized via a facile one-pot strategy. Interestingly, Fe–cat NPs show intracellular pH-responsive disassembly and release catechin molecules under the low pH of lysosomes after endocytosis. This strategy delivers catechin intracellularly and then enhances the osteogenic differentiation while inhibits the adipogenic differentiation of human adipose-derived stem cells (hADSCs). More importantly, Fe–cat NPs remodel the osteogenic immune microenvironment by resisting inflammation and promoting M2 polarization of macrophages. As a promising metal–organic nanodrug, the intracellular pH-responsive Fe–cat NPs significantly enhance the therapeutic effect of bone regneration by orchestrating osteogenic differentiation and immunomodulation, which may have great potential in bone tissue engineering.