Biomedical engineering for clinical endpoints: grand challenges where engineering meets the patient

Over the past decades, medical engineering has become embedded in nearly every aspect of modern healthcare. From the intensive care unit to the operating room and the rehabilitation clinic, patients are increasingly diagnosed, treated and, at times, kept alive by engineered devices and procedures. As outlined at the journal's inception in its original Field Grand Challenge (Pioletti, 2023), the field has grown at a remarkable pace, and nearly every major medical innovation now relies, directly or indirectly, on translating engineering concepts. Yet the value of such progress is ultimately measured where patients are treated: at the bedside, in the operating room and along the (often long) road to recovery.Here, we introduce a new section of Frontiers in Medical Engineering focused on biomedical engineering research towards clinical endpoints, namely research in which engineering principles, methods and devices are brought to patients within clinical care, and whose success is ultimately judged by outcomes in the patient (e.g. survival, complication rates or recovery of function). In what follows, we focus on three identified areas where engineering is most directly woven into clinical care: (i) organ support at the bedside, (ii) rehabilitation and assistive technologies, and (iii) surgical and interventional engineering. For each, we briefly outline where the field stands and what we see as some of the outstanding challenges. We then share some thoughts on small clinical pilot studies, where an engineering contribution meets patients for the first time, as one path of particular interest. Our hope is that the section will become a home for work that brings engineers and clinicians to the same table, with the patient as the common endpoint.Few places in the hospital rely as heavily on engineering as the intensive care unit. Mechanical ventilation, extracorporeal membrane oxygenation (ECMO) and temporary mechanical circulatory support all substitute, at least in part, for the function of failing organs. The COVID-19 pandemic served as a stark reminder of how central these technologies have become. At its peak, mechanical ventilation was arguably the most widely used form of acute organ support across the globe, and the experience gathered has since informed updated guidelines on respiratory support in acute respiratory distress syndrome (Grasselli et al., 2023). Research activity on ECMO has grown steadily in recent years, and the use of venovenous ECMO for severe respiratory failure is now supported by international guidelines (Tonna et al., 2021). In parallel, pooled data from randomized trials now inform the use of temporary mechanical circulatory support in cardiogenic shock (Thiele et al., 2024).Yet organ support remains, by design, a double-edged sword. Mechanical ventilation keeps patients alive while it can also injure the very lungs it is meant to protect (von Düring et al., 2025).Likewise, extracorporeal circuits expose blood to large foreign surfaces and non-physiological flows, such that thrombosis and bleeding remain among the most frequent complications (Chandler, 2022). In brief, these limitations are intimately tied to engineering: how mechanical loads, flows and interfaces translate into tissue damage in the patient. Such constraints are not readily captured by device settings or dose-based arguments alone. Rather, they call for experimental and clinical studies that link support strategies to biological markers of injury in the patient.A number of outstanding engineering challenges still lie ahead. First, there remains a need to move from device settings to patient outcomes and to understand which mechanical quantities (e.g. strain, flow or shear) predict injury in a given patient. Second, extracorporeal and circulatory support devices must become safer and simpler to deploy, so that they can be used beyond a handful of expert centres. Third, as automation enters the bedside (e.g. closed-loop control of ventilation or anaesthesia), such systems must be evaluated against clinical endpoints rather than technical performance alone; a recent multicentre trial, for example, found no gain in ventilatorfree days with automated closed-loop ventilation compared with protocolized conventional ventilation (Sinnige et al., 2026). Across these three challenges, these are research questions in their own right, calling for measurements and models that are tested early in patients together with clinical researchers.Stroke, spinal cord injury, limb loss as well as musculoskeletal conditions and injuries affect hundreds of millions of patients worldwide, with musculoskeletal disorders alone accounting for the largest share of the global need for rehabilitation (Cieza et al., 2020). For many of these patients, recovery of function, rather than survival, is the clinical endpoint that matters most.Beyond neurological rehabilitation, assistive biomechanical devices (e.g. orthoses, braces or soft wearable exosuits) are increasingly designed to support joints and muscles after injury or in chronic musculoskeletal conditions. Wearable exoskeletons, in particular, have drawn growing research interest in recent years, and rely on increasingly sophisticated designs and control strategies to assist walking (Siviy et al., 2023). At the same time, brain-computer interfaces are being explored to restore upper limb function after stroke (Li et al., 2025), and a Cochrane review of electromechanical-assisted gait training now provides pooled clinical evidence on its benefit (Mehrholz et al., 2020). In parallel, bionic limbs and neuroprosthetics have advanced from laboratory demonstrations towards clinical use, with neural interfaces that restore sensation and more intuitive control of prosthetic limbs (Huang et al., 2024).and what patients experience in daily life. We are well aware that engineering advances alone do not resolve this gap, which also depends on patient selection, therapy dosing and reimbursement, to cite a few. Nevertheless, we see some of the following challenges as central: (i) moving from short-term, laboratory based assessments to first studies in patients, with functional endpoints that matter to them; (ii) adapting devices to the variability between patients, and to the changes in a given patient over the course of recovery (Siviy et al., 2023); and (iii) bringing these technologies into the clinic and the home, where cost, usability and long-term adherence ultimately determine their impact, e.g. rates of upper-limb prosthesis rejection have changed little despite recent technological innovations (Salminger et al., 2022).The operating room has undergone a profound transformation over the past two decades. Robotassisted minimally invasive surgery is now routine in many specialties, and the research community has accumulated a decade of experience on how robots may assist, and increasingly act alongside, the surgeon (Dupont et al., 2021). All the meanwhile, the question has shifted from whether robots can perform surgical tasks to how much autonomy they should be given, and under which conditions. The first surgical robots with some level of autonomy have already been cleared by regulators, yet most remain at the lowest levels of autonomy (Lee et al., 2024). Equally, while artificial intelligence and haptic feedback promise to improve precision and safety, evidence of their benefit for patients remains limited.In parallel, cardiovascular interventions have moved steadily away from open surgery and towards catheter-based procedures. Here, engineering contributes on two fronts. On one hand, robotic and magnetically steered catheters are opening access to vessels that remain out of reach for manual navigation, and artificial intelligence is increasingly embedded in their navigation (Yao et al., 2026). On the other hand, transcatheter aortic valve replacement (TAVR) has become a standard of care for a growing population of patients, and patient-specific computational models of valve deployment are increasingly explored to anticipate complications such as paravalvular leakage before the procedure (Rauseo et al., 2026). Both lines of work bring engineering directly into the catheterization laboratory.Beyond the device itself, the learning curve of operators, the cost of such systems and uneven access across hospitals and countries all shape whether patients ultimately benefit. Concurrently, robotic platforms record large amounts of procedural data (e.g. instrument trajectories, forces or images), which could serve as objective measures of quality, provided they are linked to patient outcomes. A major challenge remains moving from feasibility to clinical benefit. This entails (i) defining how levels of autonomy should be validated, regulated and accepted by clinicians and patients; (ii) demonstrating that robotic and image-guided procedures, for example, improve clinical outcomes, and not only procedural metrics; and (iii) validating patient-specific planning tools for structural heart interventions against outcomes across patient populations, rather than one patient at a time.Across the three challenges outlined above, a common thread emerges. Whether the engineering contribution concerns a device, a procedure, a control strategy or a planning tool, it is ultimately judged in patients, by clinical endpoints rather than by technical performance alone. Clinical evaluation, regulatory science, usability and human factors, as well as the equity and sustainability concerns raised by Pioletti (2023), are therefore integral parts of each topic rather than standalone themes. This raises the question of how such contributions can best reach patients in the first place.Large randomized controlled trials remain the gold standard of clinical evidence, and rightly so.Yet they are costly, take many years and come late in the life of a medical technology, long after the key engineering choices have been made. All the meanwhile, the step that matters most to engineers, that is, the first use of a device or procedure in patients, remains comparatively underreported, being often regarded as too clinical for engineering journals and too preliminary for clinical ones.We argue that this gap deserves more attention. Among the many contributions the section welcomes, we see small clinical pilot studies as a path of particular interest, namely first-in-human, feasibility and early-phase studies in which an engineering contribution is tested in patients for the first time. Such studies may include a handful of volunteers and/or patients, and their aim is not to establish efficacy. Instead, they ask whether a technology can be used safely, whether it behaves in patients as it did in the laboratory, and which endpoints and patient groups a subsequent trial should target.To illustrate, a pilot study at the bedside may test whether a new support strategy changes the load on the organ as intended, as recently shown in twelve patients with acute respiratory distress syndrome, in whom ventilator settings guided by electrical impedance tomography reduced the mechanical power delivered to the lungs (Jimenez et al., 2023). In rehabilitation, a first-in-human study may follow a single patient over many months, both in the clinic and at home, as shown for a brain-spine interface that restored natural walking after spinal cord injury (Lorach et al., 2023).In the catheterization laboratory, a first-in-human study may test whether a robotic system can safely assist a structural heart intervention, as recently reported for robotic-assisted transcatheter edge-to-edge repair (Zhu et al., 2025). In each case, the study is small, but the questions it answers are precisely those that determine whether a larger trial is worth pursuing.In this spirit, the section would particularly welcome (i) first-in-human and feasibility studies of novel technologies, devices and procedures; (ii) pilot studies linking engineering parameters (e.g. device settings, control strategies or procedural planning) to early clinical endpoints; and (iii) reports that link laboratory and clinical data obtained with the same technology, following established reporting guidelines for pilot and feasibility studies.The benefit of biomedical engineering for patients will be decided, to a large extent, where research and engineering meet the patient: in the intensive care unit, throughout rehabilitation, and in the operating room and catheterization laboratory. In each case, the technology has matured to a point where the main question is no longer whether it works, but whether, for whom and under which conditions it improves clinical outcomes. Answering such questions calls for the full spectrum of research, from experimental and computational studies with a clear path to the patient, to first-inhuman and pilot studies, larger clinical evaluations, as well as reviews and perspectives.Ultimately, it requires engineering and clinical research to advance hand in hand, and it is precisely this convergence that the section aims to foster, with the patient as the common endpoint.