Tendon-muscle-nerve disconnection in chronic large and massive posterosuperior rotator cuff tears: a targeted narrative mechanistic review and hypothesis-generating framework

Anatomical repair of chronic large or massive posterosuperior rotator cuff tears does not invariably restore strength, endurance, or patient-reported function. This targeted narrative mechanistic review synthesizes cuff-specific human studies, rotator cuff animal models, and explicitly labelled non-cuff skeletal-muscle evidence to examine persistent dysfunction after repair. Its primary purpose is to calibrate evidence across mechanical load-transfer failure, selected neural modifiers, and stromal remodeling; its secondary purpose is to propose a falsifiable, hypothesis-generating tendon-muscle-nerve (TMN) framework. Human evidence is strongest for the prognostic association of fatty infiltration, atrophy, muscle volume, and tendon integrity. Suprascapular neuropathy is documented in selected patients but is not present in most chronic massive tears. Cuff-specific evidence for neuromuscular-junction remodeling is sparse and conflicting, whereas fibro-adipogenic progenitor, macrophage, extracellular-vesicle, and metabolic-fate mechanisms remain predominantly animal, ex-vivo , or extrapolative. We therefore propose that mechanical burden, defined neural modifiers, and candidate biological stage be measured separately and initially retained as continuous variables. Proposed categories and quantitative anchors require prospective testing for reliability, longitudinal stability, incremental prognostic value, and treatment-effect heterogeneity. The TMN construct is not a validated diagnosis, staging system, or treatment algorithm. Mechanical restoration remains the clinical foundation; neural and stromal interventions remain selective or preclinical research hypotheses.