*4.2. Studies with Biomechanical or Clinical Focus*

Validated models are used to comprehensively investigate biomechanical and clinical aspects of a wide range from routine scenarios to nonphysiological, or even traumatic events.

The relevance of low-dynamic everyday or work-related activities for the general population, as well as their experimental accessibility, make these scenarios among the most studied in biomechanical simulations. Therefore, numerous models exist that deal with the mechanical effects of lifting [12,13,25,46,76,77,82], everyday activities such as walking, flexion, extension, or lateral bending [15,43,69] or work-related situations such as high-frequency axial loading [17,18]. In this context, different lifting techniques were evaluated [50,51,83,117]. Accident situations were investigated by Wei et al. [16] for snowboarding and for frontal impact by Valdano et al. [14]. Incorporating noncritical higher dynamics, Raabe et al. combined a generic model of the lumbar spine [31] with a model of the lower limbs [111] to analyze the biomechanics of jogging [40]. Studies investigating specific kinematic boundary conditions usually involve an experimental setup to collect kinematic data in a healthy adult population [46,47,52,58,83]. Comparably few studies target more vulnerable populations, such as amputees [48,53] or children [27,56], who used validated models of adults and scales them according to the literature to match the average anthropometric data of children.

Regarding the influence of healthy anatomical and anthropometric and anatomical characteristics, biomechanical modeling have been used to determine the effect of spinal alignment [28,43,47], to gain insight into load sharing of passive structures of the FSU [22], the effect of ligament stiffness [65] or muscle strengthening [118].

Furthermore, MBS models can help to understand and treat pathological developing or surgically induced pathological biomechanics. Kuai et al. analyzed the impact of disc herniation on the kinetics of the spine and lower extremities during everyday activities [44].

Surgical interventions always represent a major intervention in the natural biomechanics of the musculoskeletal system. Thus, several studies on the effects of spinal fusion can be found in the literature [29,71,119]. The resulting kinematic effects of spinal fusion were investigated by Ignasiak et al., who proposed a method for the prediction of a full-body sagittal alignment including reciprocal changes as a reaction to spinal fusion [68].

#### **5. Limitations and Challenges**

It is in the nature of numerical models that they come with limitations. One of the great challenges is to keep the balance between necessary accuracy and reasonable complexity. This requires not only in-depth knowledge of the object to be modeled but also the corresponding data from experimental studies and the appropriate technical solutions for implementation. During our literature research, we were able to identify several core limitations that could be found in a wide range of MBS models of the spine and the related challenges when it came to addressing these limitations.
