Assessing the role of selected growth factors and cytostatic agents in an in vitro model of human dura mater healing

Abstract

OBJECTIVES: Cerebrospinal fluid (CSF) leaks are a common concern in skull base surgery. Appropriate dural healing is crucial to prevent CSF leaks but the entire process has been barely understood so far. Here, we review the impact of growth factors and chemotherapeutic agents on an explant culture of human dural fibroblasts and a 3D subculture grown in a collagen mesh scaffold. METHODS: Human dural specimens were harvested during surgical procedures where they would not be further used therapeutically or diagnostically. Explant cultures were grown in Petri dishes, and subcultures were grown in collagen mesh scaffolds. Insulin, fibroblast growth factor type 2 (FGF-2), and human serum were analyzed for their effect as growth factors, whereas mitomycin C, vincristine, and colchicine were analyzed for their role as inhibitors. Cell count was used as a parameter to assess the effects of these factors. In addition, the effects of human serum were assessed using collagen mesh scaffolds. RESULTS: Insulin, FGF-2, and human serum increased culture cell count; human serum also achieved an increased number of viable fibroblasts embedded in a collagen mesh. Mitomycin C, which is a mitosis inhibitor, showed no significant effect on cell count, whereas colchicine and vincristine, which inhibit both mitosis and migration, resulted in cell growth suppression. DISCUSSION: In our model, dural defect closure is achieved through cell migration rather than through cell growth. Adding growth factors to the dural suture line or into a collagen mesh might prove useful to stimulate dural closure.