This paper describes an optimized procedure to incorporate silica particles by hydrolysis/polycondensation of sodium silicate into pericardial (ECM) matrix scaffolds and points out the effect of the biocomposites on the in vitro response of macrophages by assessment the secretion of signaling molecules. Variables (concentration, pH, time) of the sol-gel process allow a gradual incorporation (0.5 to 4w%) of silica into the ECM scaffolds as confirmed by gravimetry, FT-IR, SEM and EDX microanalysis. The incorporation of SiO2 increases the resistance to in vitro degradation but not alters either denaturation temperature or free amines of non-crosslinked ECM fibrous scaffolds, however, properties achieved after crosslinking of the scaffolds with oligourethane are not modified after incorporation of silica. Despite the fact that viability of cells is gradually decreased on the ECM materials crosslinked with oligourethane and functionalized with silica, murine RAW264.7 macrophages are able to secrete b-FGF, TGF-β1 and VEGF. After 6 h of culture on ECM scaffolds that contain silica, the amount of growth factors secreted by RAW264.7 macrophages is reduced but it is sustained for 24 h compared to cells cultured on silica-free scaffolds. Human peripheral blood macrophages that proliferate on materials that contain silica show a higher production of IL-6, IL-10 or TNF-α than on the silica-free counterparts but in a time-dependent manner from one to four days of culture. Results suggest that stimulation of macrophages is induced by silica particles deposited onto the ECM fibrous network, which represents an opportunity to control the response of cells to decellularized tissue derived biomaterials through strategies intended to stimulate cells via signaling molecules secreted by macrophages.