## 4 Application Fields and Clinical Obstacles  
Medical gas plasma technology provides hemostasis in a localized, controlled, and specific manner when applied to the injured side. Major advantages include preserving tissue integrity, few side effects, and restoring physiological tissue structure (restitutio ad integrum), which is emphasized by long-term studies in vivo [66; 67]. In this view, the  
Figure 4: Putative modes of action of gas plasma during hemostasis. Created with biorender.com (accessed on 1 February 2022). application of medical gas plasma is particularly eligible for hemostasis in sensitive tissues and several types of surgery in, e.g., unintended colon tissue damage during laparoscopy or laparotomie, neurosurgical procedures, or cerebral microhemorrhages (CMBs). In gastrointestinal surgery, partial hepatectomy is associated with high mortality and morbidity rates. Patients are at particular risk for secondary bleeding, infection, and loss of liver function due to deficient surgical bleeding control [91]. Healing courses after liver and splenic resection in experimental mouse and rabbit models indicated few side effects of intra-operative bleeding control using medical gas plasma technology. Further, physiological tissue structure could be preserved, preventing major loss of functional tissue [66, 67] and emphasizing gastrointestinal surgery as a feasible application field for gas plasma-mediated blood coagulation. Preservation of functional tissue and tissue integrity is not only relevant concerning long-term follow up of patients undergoing surgical procedures. Surgical procedures that put patients at high risk for severe postoperative bleedings after sloughing of eschar, such as tonsillectomy [92], could benefit from medical gas plasma technology along similar lines. Besides surgical application fields, the ability of medical gas plasma to induce fast, local hemolysis with subsequent platelet activation and blood hemostasis could be used to stop acute bleeding, such as epistaxis originating from small artery ruptures located in the Kiesselbach's plexus. Moreover, portable medical gas plasma devices could be a significant relief for hemophilia patients. Due to a mostly inherited genetic disorder, the process of plasmatic hemostasis is heavily impaired in those patients. By that, spontaneous bleedings occur, often without any preceding visible injuries. Fast local control of such bleedings using medical gas plasma as a home care device could be a relevant, liberating benefit. Further advantages of medical gas plasma technology include simultaneous disinfection and promotion of wound healing and bleeding control, which have already been addressed in the treatment of chronic wounds [93]. In this regard, another potential benefit could be provided by applying cold physical plasma to acute nonsterile skin wounds. Clinical practice dictates open-wound care for nonsterile wounds or treatment with long-lasting vacuum-assisted wound closure, which requires inpatient treatment or drainage. Due to antimicrobial effects, blood coagulation, and wound healing stimulation, it would be conceivable to provide wound care using gas plasmas [23] (Figure 5). As overshooting ROS production is linked to increased autoimmunity and the pathogenesis of many other diseases, questioning immune-mediated complications upon exposure to gas plasma-derived ROS seems evident. Antigen-independent proliferation of T cells or generation of neo-cryptic epitopes, which might serve as autoantigens, could put patients at risk for autoimmune reactions. Medical accredited plasma devices have been investigated in clinical trials for wound care since 2010 [94], and clinical data exist from multiple dermatological centers in central Europe. Until now, no evidence indicates increased occurrence of adverse side effects and has neither been reported in follow-up studies in patients [95] nor in mice [96].