246 Chapter 8 engineering will be the integration of relevant accessory structures such as blood vessels, sebaceous glands or hair follicles to make in vitro models even more similar to the situation in patients [112,114–117]. Another appealing animal-free research strategy is the use of in silico models. In such models specific wound healing processes can be simulated and predicted using computational and mathematical models [118,119]. Collaborations have been initiated to use the animal and patient datasets generated in this thesis to support the development of in silico models for the simulation of burn wound healing and related inflammatory processes. These models are advanced tools that can incorporate the complex mechanisms of burn injury and might be used for the prediction of complications and for therapeutic decision-making. Nevertheless, even with these animal-free approaches, animal experiments cannot be abandoned completely and remain necessary. For example, animals will still be needed for safety and dose-finding studies in drug development. In such situations, we recommend that experiments should be set up with caution for factors that can influence immune-related outcomes in order to correctly interpret the results, as we discussed in Chapter 2 and Chapter 3. Many studies failed to adhere to the ARRIVE guidelines and contacting authors for data requests often remained unanswered, making it difficult or impossible to reuse data in advanced analyses and complicates study quality assessment [120–122]. Future research will most certainly benefit from more standardized designs, complete reporting and effortless access to raw datasets. Furthermore, burn care in general could be improved by participation from health care workers who bring approaches from different disciplines, including clinical (e.g. patients, physicians, surgeons, nurses, therapists), biomedical (e.g. biologists, engineers) and computational sciences (e.g. mathematicians, biostatisticians) to better understand and predict burn-induced pathologies. The combination of different viewpoints, including that of burn patients, can possibly lead to new insights, diagnostic tools and interventions, advancing both burn research and care. Diagnostics and prediction of clinical course Some burn patients develop systemic inflammatory response syndrome (SIRS), while others develop progressive immunosuppression. These opposing conditions can even occur at the same time and are sometimes described as sepsis [123]. These conditions are likely linked to the persistent acute phase response and impaired function of the adaptive immune system. There is a strong need for better tools to diagnose and predict the clinical course that patients will follow so that appropriate therapy can be applied as soon as possible. Burn patients are routinely monitored by checking clinical parameters such as body temperature, white blood cell count, c-reactive protein and procalcitonin
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