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Dr Hubertus Strughold is the ‘Father of Space Medicine’. He first coined the term ‘space medicine’ in 1948 and was the first and only Professor of Space Medicine at the U.S. Air Force School of Aerospace Medicine. Space medicine began as a niche field to understand the intricacies of human physiology when put in space. Space surgery is a sub-discipline of space medicine with close associations to other space-related fields, pioneered by Dr G. L. Iaroshenko in 1967 with his work in rodents at the Russian Space Agency. Early space programmes like Mercury, Gemini and Apollo concentrated primarily on survival and basic physiological monitoring. In those programmes, medical emergencies were regarded as improbable, and plans for serious interventions, including surgery, were minimal (Barratt & Pool, 2008). The ISS shifted the paradigm, highlighting the need for a comprehensive medical infrastructure to enable human habitation in space. Astronauts underwent extensive health screenings and trained for emergency procedures; however, the ability to perform invasive surgery remained theoretical (Nicogossian et al., 1989). Today, Artemis missions and the vision of colonising Mars and deep space travel are becoming ventures beyond the skies. As such, steps and preparedness are imperative for long-duration space travel, including being able to execute medical and surgical treatment on board a spaceship and in challenging surroundings. Those challenges represent critical aspects of space medicine and performance. The ability to perform surgery in space requires a different set of training, skills and capacities. The concept of conducting surgery in microgravity or the extremely challenging environments on the Moon or Mars has never been considered. It will undoubtedly pose unique risks, technical demands, modified skills and innovative solutions. This article explores the multifaceted field of space surgery, covering its historical context, challenges in performing surgical procedures in space, technological innovations, ethical considerations, and the pathway toward enabling safe and effective surgery beyond Earth. No surgeries have been performed on humans during a spaceflight; however, space exploration has always represented extending the boundaries of scientific knowledge and the supremacy of technological advancement. It also introduced the concept of survival as a species on other planets. The first boundaries we crossed were putting humans on the Moon and living on the international space station (ISS). Performing surgery in space is not without challenges. Surgeons’ dexterity, stability of surgical instruments and awareness of their surroundings are paramount during surgical procedures. Microgravity imposes many issues in space that must be controlled to avoid immediate complications. Blood and other bodily fluids tend to float in microgravity, complicating visualisation and suction and contaminating the surgical field (Campbell & Billica, 1994). A strategy with zero risk must be mandated to prevent untoward hazards. Real-time communication with Earth-based medical experts has been carried out as an exercise and was deemed feasible as observed on the ISS; however, with plans to travel into deep space, this exercise becomes futile. For instance, a communication delay of up to 20 min one-way between Earth and Mars makes telemedicine impractical for urgent surgical intervention (Putcha et al., 1999). Moreover, psychological stress and the confined environment can affect the patient and the surgical crew, potentially compromising surgical outcomes (Antonsen et al., 2014). Due to a stringent strategy for weight control on a space mission, surgical instruments, medications and diagnostic tools essential for mission and crew safety will undoubtedly add to the mass and volume constraints. Resupply from Earth may be delayed or impossible during deep space missions (Ball & Evans, 2001). Appendicitis, a common acute abdominal condition, which has already prompted pre-emptive appendectomies in astronauts during early programmes. Traumatic injuries, such as blunt abdominal trauma or penetrating wounds from equipment or accidents within the spacecraft, potentially involving hollow viscera and necessitating emergency laparotomy. Kidney stones, which are more likely in space due to bone demineralisation and altered fluid dynamics leading to calcium imbalances. Infections requiring abscess drainage, particularly as the immune system is known to be dysregulated in space, increasing susceptibility. Orthopaedic injuries, such as fractures or dislocations, possibly from exercise equipment or during extra-vehicular activity (EVA), compounded by muscle and bone loss in microgravity. While these are rare, the risks and consequences of being unprepared can be fatal. This risk has prompted space agencies to explore various contingency plans, from conservative medical treatment to the development of robotic surgical systems (Doarn & Nicogossian, 2012). That being said, a complete surgical system for space missions must integrate not only operative capability but also preoperative diagnostics, intraoperative support and postoperative care. Diagnostic imaging in space remains limited, with ultrasound being the most feasible tool due to its portability and lack of ionising radiation. However, it requires trained personnel and does not replace the capabilities of radiography or computed tomography, which remain too bulky or technically complex for current missions. Anaesthesia presents another significant challenge. Delivery systems must be simplified and autonomous, given the absence of specialist anaesthetists. Inhalational agents pose risks in closed-loop air systems, while intravenous sedation and regional techniques must be adapted for altered pharmacodynamics in microgravity. Postoperative care is similarly constrained. Sterile storage, temperature control and expiration issues limit the supply of blood products, while immune suppression and radiation exposure complicate wound healing. Compact, multi-use devices for haemodynamic monitoring, sterilisation and telemetric data relay are being considered, but none have yet been validated in operational space conditions. Understanding physiological effects is critical for developing surgical techniques and recovery protocols suitable for long-duration missions. As part of surgical recovery, patients undergo various physiological processes to allow tissue and wound healing. Prolonged exposure to the space environment can impede recovery, potentially counterbalancing the physiological process and affecting other tissues and organs, complicating surgical recovery. This can lead to muscle atrophy and bone demineralisation in microgravity, impairing healing and increasing the risk of fractures or complications during emergency orthopaedic surgery (Smith & Heer, 2002). The cascade of physiological events can cause immune system impairment and lead to prominent dysregulation. The outcome of reducing the body's ability to fight infection is particularly concerning in post-surgical patients, who may already be vulnerable to pathogens (Crucian et al., 2008). Moreover, fluids shift toward the upper body and head in microgravity, increasing intracranial pressure and potentially altering cardiovascular dynamics. This fluid shift can interfere with anaesthetic management and complicate intraoperative fluid balance (Seedhouse, 2020). Exposure to radiation is inevitable in deep space travel. As with astronauts, space patients are exposed to higher levels of cosmic radiation in deep space, which may impair tissue regeneration, negatively affect wound healing, and complicate the long-term outcomes of surgical procedures. Compounding the multiple scenarios, one must not forget the psychological impact of deep space travel. For a patient in space, isolation, confinement and distance from Earth can lead to anxiety, depression or cognitive decline, which may influence surgical decision-making or the ability to comply with post-operative care protocols (Kanas et al., 2009). Figure 1 illustrates several examples of the impact of microgravity on human physiology. Robotic-assisted surgery has been applied and provides precision, control and excellent outcomes in various surgical fields. Space robotic systems must be lightweight, compact and durable. NASA and commercial partners are actively developing miniaturised robotic arms and instruments that can be stored efficiently aboard spacecraft and deployed rapidly in emergencies. They experimented with systems like the Robonaut and miniaturized in vivo robotic assistant (MIRA), which could allow surgeons to operate remotely on space patients (Figure 2). However, robotic surgery continues to be one of the most promising avenues for addressing the surgical needs of space missions. Yet, telerobotic systems such as the MIRA robot have been designed to perform surgeries via remote control. These systems allow Earth-based surgeons to guide robotic instruments with high precision. However, for missions to Mars or beyond, communication delays may hinder effective real-time operation, and the challenge remains the lapse and latency in signal transmission for distant missions (Satava, 2002). A semi-autonomous system has been innovated and developed to address this issue, allowing pre-programmed robots to perform surgery with minimal need for actual surgeon perception, application and intervention. These systems promise to perform surgical tasks and execute complex procedures when communication loss and latency become problematic. Whether this will lead to a surge in performance and minimise human-related error is yet to be revealed, as no study has compared surgical experience to autonomous capability in similar conditions to deep space. The concept is difficult to replicate and test, and ethics approval is required to test on real-time patients in a complex setting. Hence, although the technology is here, its application and assessment are complex. Augmented reality and virtual reality technologies have been proposed and are being tested for medical training and surgical guidance. These systems can simulate zero-gravity surgeries and provide real-time overlays of anatomical structures during procedures. An example of a postulated trauma pod surgical module is shown in Figure 3. Diagnostic advancement has surged in current practice, and related experience in using telemedicine and artificial intelligence (AI) diagnostics has been reported. Combined with telemedicine, AI algorithms can guide non-specialist crews through procedures. AI can also monitor vital signs and suggest real-time adjustments (Ricci et al., 2020). Closed-loop systems use AI and real-time data to monitor physiological changes and autonomously adjust interventions. These could reduce human error and support critical decision-making when medical professionals are unavailable. However, surgical and physiological understanding, education, training and performance are limitations. Training an astronaut to lead a surgical activity can be time-consuming and a burden. Robotic innovation must be coupled with reliability, which is paramount in space missions. The design should be optimised to operate without frequent maintenance, self-diagnose errors and execute repair procedures. As such, redundant systems and fail-safes are being integrated to ensure the robotic system functions effectively in all conditions. Moreover, the systems must be compact and multifunctional. These include sterilisable instruments, diagnostic devices and tools designed to work in microgravity. Modular designs allow customisation based on mission length and crew composition (Shelhamer, 2016). Bioprinting and tissue engineering are other tech innovations that have leapt in space surgery and emergency settings. Those capabilities offer robust solutions that can support organ failure. Experiments aboard the ISS have demonstrated the feasibility of 3D bioprinting in microgravity. Though in its infancy, this technology could one day enable on-demand generation of tissue grafts or organs (Kang et al., 2016). Ethical reflection is required during space flights and should be considered standard with the current space travel race. Informed consent must include the possibility of surgical emergencies and the limitations of treatment options. Ethical dilemmas arise when deciding between returning to Earth for treatment or attempting risky procedures in space (Charteris & Hudson, 2019). Medical issues may impact mission success, raising questions about privacy versus the right to know. Decision-making protocols must be established for emergencies requiring surgical intervention. Achieving reliable surgical capability in space will require collaboration among engineers, biologists, physicians, computer scientists and space agencies. Integrating these disciplines will accelerate the development of space-rated surgical tools, autonomous systems and reliable training protocols (Kochan & Cermack, 2021). Several ground-based studies simulate surgery in space-like conditions. Parabolic flights offer short periods of microgravity, allowing researchers to test instruments and procedures. NASA extreme environment mission operations (NEEMO) uses underwater habitats to simulate isolation and medical scenarios (Jones & Polk, 2015). The European space agency (ESA), NASA and private companies have invested in analogue missions and virtual environments to explore surgical training and robotic systems. These simulations provide valuable data but fail to replicate deep space conditions (Hill et al., 2021). International cooperation will be essential in setting ethical guidelines, sharing resources and harmonising protocols across spacefaring nations. Private entities like SpaceX, Blue Origin and Axiom Space are accelerating human access to space. With ambitions for lunar bases and Mars colonisation, the private sector's role in advancing space medicine is critical. Investment in health infrastructure, including surgical capability, will be essential for sustainable human presence. These companies are already working on modular habitat systems and have partnered with universities to explore telehealth platforms and autonomous systems. The flexibility and innovation private space enterprises offer can drive rapid advancements that complement governmental space programmes. Institutions like the United Nations Office for Outer Space Affairs (UNOOSA) may play a role in creating medical governance frameworks for space exploration (UNOOSA, n.d.). Furthermore, should space tourism become more widespread in the future, medical preparedness would likely shift from being a government-dominated responsibility to one that involves commercial operators. This prospective transition underscores the need to begin planning for standardised training, portable diagnostic tools and compact surgical kits that can be used by minimally trained personnel. While promising progress has been made in space surgery research, current developments remain largely theoretical or experimental. Many innovations – such as autonomous robotic surgery, AI-driven diagnostics and bioprinting – require extensive validation in actual space environments. Simulated and analogue studies cannot fully replicate the complex conditions of microgravity or deep space radiation exposure. Moreover, the ethical frameworks and operational guidelines for invasive procedures in extraterrestrial settings are still nascent. Long-term data on wound healing, immune response and infection control in microgravity are limited. Surgery in space is no longer a far-fetched idea but a vital component of future exploration. As missions become longer and more distant, the ability to address medical and surgical emergencies through surgical means will become indispensable. Interdisciplinary collaboration is essential to overcome the formidable challenges of surgery in space. The future among the stars depends on the scalpel as much as the spaceship and team. All authors have approved the final version of the manuscript and agree to be accountable for all aspects of the work. All persons designated as authors qualify for authorship, and all those who qualify for authorship are listed. D.M.B. is Editor-in-Chief of Experimental Physiology, Chair of the Life Sciences Working Group, member of the Human Spaceflight and Exploration Science Advisory Committee to the European Space Agency and member of the Space Exploration Advisory Committee to the UK and Swedish National Space Agencies. D.M.B. is also affiliated to Bexorg, Inc. (USA) focused on the technological development of novel biomarkers of cerebral bioenergetic function and structural damage in humans. None.