Tendons play a crucial role in the musculoskeletal system, connecting muscles to bones and enabling efficient force transfer. However, they are prone to acute and chronic injuries, which, if not properly repaired, can significantly impair function. Tendinopathy, a prevalent condition affecting approximately 20% of musculoskeletal complaints, arises from an imbalance between micro-injury accumulation and repair processes. The extracellular matrix (ECM) of tendons is a hierarchical structure comprising collagen fibrils, proteoglycans, and glycoproteins that regulate organization, hydration, and mechanical properties. Mechanotransduction pathways, mediated by integrins and focal adhesion complexes, activate signaling cascades such as MAPK/ERK and PI3K/Akt, driving tenocyte gene expression and ECM remodeling. Adaptations to load involve region-specific remodeling, with tensile regions favoring aligned Type I collagen and compressive regions promoting proteoglycans like aggrecan. Stress shielding or reduced loading disrupts these pathways, leading to matrix disorganization and inflammation, predisposing tendons to degenerative changes. Insights into these molecular mechanisms inform rehabilitation strategies to enhance tendon repair and mitigate tendinopathy progression in both athletic and general populations.

Ligaments are biomechanically specialized connective tissues that maintain joint stability and guide motion under complex loading conditions. At the cellular and molecular levels, ligament homeostasis is governed by fibroblast-like cells (ligamentocytes) embedded in an intricately organized ECM composed predominantly of type I collagen, with contributions from type III collagen, elastin, proteoglycans, and glycoproteins. These cells continuously sense and respond to mechanical stimuli—tension, compression, and shear—through mechanotransduction pathways involving integrins, focal adhesions, cytoskeletal remodeling, and mechanosensitive ion channels. Downstream signaling cascades, including MAPKs and PI3K/AKT, integrate biomechanical cues with growth factor and cytokine signaling to fine-tune gene expression, collagen fibrillogenesis, and ECM turnover. Distinct from tendons, ligaments must adapt to multidirectional loads, resulting in unique ECM compositions and cellular phenotypes. Appropriate mechanical loading maintains collagen alignment, promotes ECM integrity, and stabilizes the ligament cell phenotype. By contrast, insufficient or excessive load alters the molecular balance, triggering catabolic processes, inflammation, and disorganized ECM assembly. This delicate equilibrium also underlies the ligamentization observed in ACL graft remodeling, where controlled mechanical environments and molecular interventions accelerate the acquisition of ligamentous properties. Emerging insights into transcriptional and epigenetic regulation, growth factor-mediated cues, and cytokine-driven responses offer avenues to engineer ligament-like tissues and optimize recovery strategies. By leveraging molecular knowledge of cell–matrix interactions, growth factor profiles, and genetic/epigenetic modulators, clinicians and researchers can design tailored loading protocols, biomimetic scaffolds, and regenerative therapies. These approaches aim to restore ligament functionality, enhance graft integration, and prevent degenerative changes, ultimately improving patient outcomes in ligament injury repair and reconstruction.

Stroke, a major cause of disability worldwide, necessitates comprehensive rehabilitation, with nutrition playing a pivotal role in recovery. Our systematic review assesses the impact of nutritional interventions on stroke survivors' rehabilitation. Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically searched PubMed, Embase, Web of Science, and Scopus, using keywords related to stroke rehabilitation and nutrition. Studies were selected based on criteria emphasizing dietary interventions and their effect on functional recovery in stroke patients. The review involved detailed data extraction and synthesis, covering study design, participant characteristics, interventions, and outcomes. Five studies met our inclusion criteria, encompassing longitudinal and prospective studies, retrospective cohorts, and randomized controlled trials. These studies highlighted the importance of early nutritional assessment, particularly for sarcopenic patients, and the role of energy and protein intake soon after a stroke. Findings indicated high nutritional risk correlated with poorer functional outcomes and increased inflammation. Tailored dietary support appeared beneficial for muscle mass maintenance and overall functional recovery, especially in older patients. Our review emphasizes the critical role of nutritional interventions in stroke rehabilitation. It suggests that personalized nutritional strategies can positively impact functional recovery, notably in older and nutritionally vulnerable stroke survivors. These insights underscore the necessity of integrating dietary assessments and interventions into standard stroke rehabilitation protocols, advocating a holistic approach to patient care.

The knee joint is a weight-bearing structure that endures varied mechanical stresses in daily and athletic activities. Its cells convert these stresses into biochemical signals through mechanotransduction, prompting changes essential for joint health, repair, and adaptation. Understanding these processes is pivotal for developing rehabilitation strategies that address injuries and degenerative conditions like osteoarthritis. Different loading modalities—compression, tension, shear, and hydrostatic pressure—impact knee tissues (cartilage, synovium, ligaments, and tendons) and their resident cells (chondrocytes, synoviocytes, and fibroblasts). Chondrocytes adjust extracellular matrix synthesis to maintain cartilage integrity, while synoviocytes regulate synovial fluid components crucial for lubrication. Fibroblasts modulate collagen production, preserving ligament and tendon strength. Underlying these activities are key signaling pathways (e.g., MAPK, NF-κB, and Wnt) that regulate gene expression and cellular metabolism in response to mechanical stimuli. By linking basic mechanobiology insights to clinical practice, clinicians can tailor therapeutic interventions—such as controlled loading, exercise regimens, manual therapy, and orthotic devices—to optimize tissue repair, restore function, and prevent further degeneration. This mechanotransduction-focused approach offers a comprehensive framework for improving knee joint health and enhancing rehabilitation outcomes.

ACL injuries present significant challenges in sports medicine, particularly in restoring knee joint function and preventing further complications like subsequent injuries or post-traumatic osteoarthritis. Traditional rehabilitation techniques, which often rely on pre-planned exercises and standardized assessments, may not adequately prepare athletes for the unpredictable nature of sports. This paper argues for a comprehensive approach that recognizes ACL injuries as failures of complex nonlinear systems rather than merely biomechanical deficiencies. The complexity of ACL injuries involves a dynamic interplay of individual skills, team dynamics, and external conditions. Traditional rehabilitation approaches that focus solely on biomechanical factors overlook the critical role of interpersonal dynamics and sensorimotor control. The brain’s integration of sensory information to form a comprehensive environmental representation is vital for motor actions. Disruptions in this sensorimotor feedback loop can impair motor control, increasing the risk of ACL injuries. Effective rehabilitation should enhance sensory integration and feedback mechanisms, improving motor control and reducing re-injury risk. Addressing proprioceptive deficits and arthrogenic muscle inhibition (AMI) is crucial for successful rehabilitation. Neurocognitive training, focusing on enhancing decision-making and motor responses, is essential for sports performance and injury prevention. Techniques like neurofeedback training can optimize brain activity patterns, leading to better motor responses and adaptation to dynamic environments. Psychological factors such as motivation, anxiety, and fear significantly influence recovery. Integrating psychological support into rehabilitation programs can address these factors, leading to more comprehensive and effective recovery strategies. Innovative rehabilitation approaches, including EMG biofeedback, motor imagery, and virtual reality-based training, can enhance reactive motor planning and adaptability, preparing athletes for the demands of their sport. The future of ACL rehabilitation lies in embracing the complexity of the sensorimotor system and developing multidisciplinary interventions that promote beneficial neuroplasticity. Advances in neuroscience and technology, such as artificial intelligence, can lead to more personalized and effective rehabilitation programs. Recognizing and addressing the multifaceted nature of ACL injuries can significantly improve rehabilitation outcomes, ensuring athletes can safely and effectively return to their sports.

The knee is a mechanically demanding synovial organ in which joint loading, tissue deformation, cellular mechanotransduction and matrix turnover are coupled. This narrative review critically links those scales and asks where the evidence is sufficiently mature for mechanistic or clinical inference. PubMed/MEDLINE and Europe PMC were searched from database inception to 20 July 2026 using structured terms for knee biomechanics, cartilage and osteochondral mechanobiology, finite element modelling, mechanosensitive channels, osteoarthritis, machine learning and digital twins. Landmark studies were selected for foundational models, while recent studies were prioritised for causal experiments, validation and translation. Instrumented implants show that common activities generate tibiofemoral forces of several times body weight, but tissue-level exposure also depends on muscle co-contraction, geometry and material properties. Biphasic and fibril-reinforced models explain how those loads become stress, strain, fluid pressure and osmotic signals. At the cell scale, TRPV4 and PIEZO1/2 participate in overlapping, context-dependent calcium signalling rather than a universal protective–pathological binary; most causal evidence remains preclinical. Osteoarthritis is therefore framed as a mechanically amplified feedback process involving cartilage, bone, synovium and systemic modifiers. Computational degeneration models and machine-learning surrogates are increasingly informative, although prospective validation, parameter identifiability and uncertainty propagation remain limiting. The review’s added value is an explicit transmission-and-validation framework that connects whole-joint observables to molecular responses while labelling the evidence source and translational readiness at every step.