Nano-layered Tendon Patch to Orchestrate Timely Interactions between Tendon Stem/Progenitor Cells and Macrophages

Here, we present a novel, micro-thin, nano-layered patch that employs Layer-by-Layer (LbL) self-assembly for the precise controlled release of small molecules, Oxo-M and 4-PPBP, to address this technical challenge. This novel combination of small molecules exhibits distinct functions in modulating the polarization of macrophages and the tenogenic differentiation of tendon stem/progenitor cells (TSCs).

The customized, temporal release of these small molecules effectively modulated the critical crosstalk between TSCs and macrophages, thereby promoting regenerative tendon healing. The nano-LbL tendon patch successfully mitigated early inflammation, promoted matrix synthesis, and regulated later tissue remodeling in vivo. Robust scRNA-seq and CellChat analysis delineated the temporal-orchestrated communication between cell types across healing phases, confirming the critical interplays between TSCs, tenocytes, and macrophages.