A decade ago, gene therapy seemed to be a promising approach for the treatment of chronic limb-threatening ischemia, providing new perspectives for patients without conventional, open or endovascular therapeutic options by potentially enabling neo-angiogenesis. Yet, until now, the results have been far from a safe and routine clinical application. In general, there are two approaches for inserting exogenous genes in a host genome: transduction and transfection. In case of transduction, viral vectors are used to introduce genes into cells, and depending on the selected strain of the virus, a transient or stable duration of protein production can be achieved. In contrast, the transfection of DNA is transmitted by chemical or physical processes such as lipofection, electro- or sonoporation. Relevant risks of gene therapy may be an increasing neo-vascularization in undesired tissue. The risks of malignant transformation and inflammation are the potential drawbacks. Additionally, atherosclerotic plaques can be destabilized by the increased angiogenesis, leading to arterial thrombosis. Clinical trials from pilot studies to Phase II and III studies on angiogenic gene therapy show mainly a mixed picture of positive and negative final results; thus, the role of gene therapy in vascular occlusive disease remains unclear.
Introduction: Oxidized regenerated cellulose-based (ORC-TABOTAMP), oxidized non-regenerated cellulose-based (ONRC-RESORBA CELL), and gelatinbased (GELA-GELITA TUFT-IT) hemostats are commonly used in surgery. However, their impact on the wound healing process remains largely unexplored. We here assess time-dependent effects of exposure to these hemostats on fibroblast-related wound healing processes. Material and methods: Hemostats were applied to fibroblast cell cultures for 5-10 (short-), 30 and 60 min (intermediate-) and 24 h (long-term). Representative images of the hemostat degradation process were obtained, and the pH value was measured. Cell viability, apoptosis and migration were analyzed after the above exposure times at 3, 6 and 24 h follow-up. Protein levels for tumor necrosis factor α (TNF-α) and transforming-growth factor β (TGF-β) were assessed. Results: ORC and ONRC reduced pH values during degradation, while GELA proved to be pH-neutral. Hemostat structural integrity was prolonged for GELA (vs. ORC and ONRC). TGF-β and TNF-α levels were reduced for ORC and ONRC (vs. GELA and control) (p < 0.05). Further, exposure of ORC and ONRC for longer than 5-10 min reduced cell viability vs. GELA and control at 3 h post-exposure (p < 0.05). Similarly, cell migration was impaired with ORC and ONRC exposure longer than 60 min at 24 h follow-up (p < 0.05). Conclusions: Short-term exposure to ORC and ONRC impairs relevant wound healing-related processes in fibroblasts, and alters protein levels of key mediating cytokines. GELA does not show similar effects. We conclude that GELA may be preferred over ORC and ONRC over short-, intermediate-and long-term exposures. Future validation of the clinical relevance is warranted.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.