Musculoskeletal ultrasound-guided cellular therapy: Current applications and future directions in skeletal muscle regeneration.

Skeletal muscle exhibits robust intrinsic regeneration after acute injury, yet severe, chronic, or age-related damage commonly culminates in fibrosis, fatty infiltration, and lasting functional impairment. This review integrates the cellular and molecular biology of successful healing spanning inflammation resolution, satellite-cell activation, fibro-adipogenic progenitor regulation, angiogenesis, and extracellular-matrix remodeling with the key failure modes that cellular therapies seek to overcome. It evaluates an expanding portfolio of platforms (mesenchymal stromal cells, satellite cells, iPSC-derived myogenic progenitors, exosomes, secretome, and biomaterial scaffolds) that act primarily through paracrine, immunomodulatory, and differentiative mechanisms, while acknowledging persistent translational barriers of low engraftment, immunogenicity, and scalability. Musculoskeletal ultrasound is positioned as a pivotal enabling technology: high-frequency B-mode, Doppler, elastography, and contrast-enhanced imaging provide real-time lesion mapping, vascular targeting, injectate tracking, and non-invasive longitudinal biomarkers of perfusion and stiffness. Sonoporation further enhances cell/exosome uptake and homing. Preclinical studies consistently show 2-5-fold gains in retention and functional recovery with ultrasound-guided versus blind delivery; clinical evidence, though still early-phase, reports acceptable safety and modest signals of benefit in sarcopenia, volumetric muscle loss, and Duchenne dystrophy. The review highlights how ultrasound-guided delivery, combined with optimized cellular platforms and biomaterials, addresses key translational barriers and proposes a realistic 2025-2040 roadmap centered on standardization, AI navigation, personalized hypoimmunogenic products, synergistic combinations (cells+biomaterials+sonoporation), and adequately powered RCTs with quantitative imaging endpoints. When these milestones are achieved, ultrasound-guided cellular therapies will offer a transformative solution for conditions in which endogenous repair fails.