Cutaneous chronic wounds remain a major clinical challenge which requires the development of novel wound dressings. Previously, we showed that collagen-silica nanocomposites consisting of polyethyl-eneimine (PEI)-DNA complexes associated with silica nanoparticles (SiNP), collagen hydrogel and 3T3 fibroblasts, can work as a local "cell factory". Indeed, the "in-gel" transfection leads to a sustained production and release of biomolecules. Herein, we further explored the possibility for nanocomposites to deliver interleukin-10 (IL-10), a potent anti-inflammatory cytokine, which favors tissue repair. Its anti-inflammatory effect was evaluated in an in vitro inflammation model carried out by LPS (lipopolysacchar-ide) activation of macrophages embedded in collagen gel. The IL-10 synthesis from nanocomposites was detected over one week in the range of 200-400 pg mL −1 and reached a maximum at day 5 without any observed cytotoxic effects. PEI 10-SiNP outperformed free PEI 10 and PEI 25-SiNP, implying that the introduction of SiNP improved the transfection efficiency of low M w of PEI. In addition, the structure and mechanical properties of collagen-silica nanocomposites were stable over one week. Subsequently, the ability of nanocomposites to modulate inflammation was tested in a 3D model of inflammation. The decrease of TNF-α and IL-1β gene expression by 20-80% indicated successful inhibition of inflammation by IL-10 released from nanocomposites. Taken together, the nanocomposites are capable of producing effective doses of IL-10 which inhibit the synthesis of pro-inflammatory cytokines and favor the expression of wound healing cytokines. Therefore, the as-constructed 3D gene delivery system represents a promising strategy for the controlled release of therapeutic biomolecules favoring cutaneous wound healing.