Inhibiting muscle degeneration in rotator cuff tears: integrative biologic approaches targeting regeneration, fibrosis, and metabolism.

Rotator cuff (RC) tears are commonly associated with progressive muscle atrophy, fatty infiltration, and fibrosis, which often persist despite successful tendon repair and remain major barriers to functional recovery and structural integrity. These degenerative muscle changes are not sufficiently addressed by tendon-focused surgical approaches and contribute significantly to poor clinical outcomes and high retear rates. In response, biologically targeted therapies have emerged to directly modulate the cellular and molecular mechanisms underlying muscle degeneration. Current strategies focus on 3 major approaches: regenerative cell-based therapies that promote muscle regeneration and suppress fibrosis; signaling pathway modulation to disrupt pathological tissue remodeling; and metabolic interventions aimed at restoring mitochondrial function and correcting lipid metabolism. Central to these strategies is the regulation of dysfunctional cellular populations within the muscle microenvironment, particularly those responsible for fibrotic and adipogenic changes. This article is a narrative literature review summarizing recent preclinical and early clinical evidence, incorporating representative quantitative findings, and acknowledging key limitations of the available studies. By integrating these emerging biologic approaches, this review provides an updated perspective on therapeutic strategies for RC muscle degeneration and evaluates their translational potential for future clinical applications.