Stable fibroblast growth factor 2 (FGF2-STAB®) induced neovascularization in dermal substitutes

Neovascularization, the formation of new blood vessels, is crucial for effective wound healing and tissue regeneration. Growth factors, such as fibroblast growth factor 2 (FGF2), play a key role in this process. Our research focused on the preclinical application of a stabilized form of FGF2 (FGF2-STAB®) to enhance neovascularization. We developed a novel dermal substitute containing FGF2-STAB® and confirmed its morphology using scanning electron microscopy. In an in vivo study using 10 female pigs, we created six full-thickness wounds on each subject, applying the dermal substitute and a skin graft in a single-step procedure. We performed VEGF-A gene expression analysis and histological evaluations at multiple time points over six months. Vascularization was analyzed from histological samples with Ridge detection and ImageJ analysis software. Our results showed that while VEGF-A gene expression was comparable among all groups during the first month, a significant increase was observed at the three-month follow-up in groups treated with FGF2-STAB®. The 1 µg/ml concentration was particularly effective at this point. One week after surgery, all dermal substitute (DS) groups containing FGF2-STAB® showed a higher median area density (AD) compared to the control groups. This difference was statistically significant when comparing specific concentrations of FGF2-STAB®, particularly at 0.1 µg/ml and 1 µg/ml, to the control groups. At two weeks, the higher AD values in the FGF2-STAB® groups persisted. Over time, AD values decreased across all groups at subsequent time points (1, 3, and 6 months post-surgery). The number of blood vessels (NV) parameter followed a similar trend to AD. During the first two weeks, NV values increased in all groups, followed by a reduction in later periods. Our study highlights the direct role of FGF2-STAB® in promoting neovascularization, suggesting that this process may not be solely dependent on VEGF-A signaling.