Silicified collagen materials: Modulation of the in vitro and in vivo response

Abstract

Collagen derived materials offer distinct advantages over synthetic polymers, considering their natural inherited biocompatibility and mechanical properties. However, because of the extraction procedure, the latter frequently need to be enhanced through the use of different crosslinking methods. Aldehydes are often used for the stabilization of biomaterials but the introduction of crosslinkers slightly alters the protein's surface reactivity hence calling for new biocompatibility studies. At the same time, silicate modification of natural polymers has gained interest within the biomaterials field for their strengthening potential and ease of manipulation, giving rise to different surfaces and bulk materials. In the present work, collagen gels modified with glutaraldehyde (ColGA) or glutaraldehyde and an aminosilane (ColGASi) were evaluated in vitro and in vivo with the aim to obtain biomaterials for wound dressings. The results obtained were compared to those derived from unmodified collagen matrices (Col). In vitro assays focused on the interaction of the materials with elements present in the human blood whereas in vivo assays evaluated their ability to support cell proliferation and angiogenesis for a period of 30 days in a rodent model. Col gels induced an increase in platelet aggregation while ColGA gels decreased it. On the other hand, ColGASi had no effect on platelet aggregation but induced IL-1β and nitric oxide platelet secretion. All gels induced lower IL-6 levels in PMN cells cultures when compared to controls. Col and ColGA gels decreased IL-1β concentration whereas ColGASi induced high expression of TGF-β in PMN cells. All gels decreased nitric oxide secretion but Col and ColGA gels increased IL-1β production by monocytes. Definitely, all gels induced an anti and pro-inflammatory profile depending on the cell type with which they interact. In vivo, an increased cellular infiltration was observed along with new blood vessel formation in those matrices containing silicified collagen, while glutaraldehyde fixed collagen induced a foreign body reaction and appeared surrounded by a fibrous capsule after 30 days of subcutaneous implantation. Overall, the results obtained show that the silicification of collagen has advantages not only through the enhancement of its mechanical properties but also through the stimulation of the integration of the material with the surrounding tissue.