This paper reports the structure–property relationship of novel biomedical hydrogels derived from collagen, water-soluble oligourethanes, and silica.

Injectable gel based on collagen, oligourethanes and silica acts as a delivery vehicle for macrophages primed for an anti-inflammatory response.

The polarization of macrophages M0 to M1 or M2 using molecules embedded in matrices and hydrogels is an active field of study. The design of biomaterials capable of promoting polarization has become a paramount need nowadays, since in the healing process macrophages M1 and M2 modulate the inflammatory response. In this work, several immunocytochemistry and ELISA tests strongly suggest the achievement of polarization using collagen-based membranes crosslinked with tri-functionalized oligourethanes and coated with silica. Measuring the amount of TGF-β1 secreted to culture media by macrophages growth on these materials, and quantifying the macrophage morphology, it is proved that it is possible to stimulate the anti-inflammatory pathway toward M2, having measurements with p ≤ 0.05 of statistical significance between the control and the collagen-based membranes. Furthermore, some physicochemical characteristics of the hybrid materials are tested envisaging future applications: collagenase degradation resistance, water uptake, collagen fiber diameter, and deformation resistance are increased for all the crosslinked biomaterials. It is considered that the biological and physicochemical properties make the material suitable for the modulation of the inflammatory response in the chronic wounds and promising for in vivo studies.