Pathophysiology and healing of insertional Achilles tendinopathy: Current concepts.

Insertional Achilles tendinopathy (IAT) is a challenging condition that significantly impacts athletes and physically active individuals, often leading to chronic pain and impaired performance. IAT is characterized by a complex interplay of mechanical stress, vascular impairment, inflammatory responses, and extracellular matrix (ECM) dysregulation at the Achilles tendon insertion. This review integrates recent advancements in the understanding of IAT pathophysiology, with focus on the effects of tensile and compressive loads, intratendinous pressure changes, tissue hypoxia, and ECM water balance. Emerging evidence indicates that mechanical loading influences tendon homeostasis through mechanotransduction, leading to ECM remodeling and fibrocartilaginous adaptation. Although appropriate compressive loading is necessary to maintain ECM homeostasis and fibrocartilage regeneration, excessive or abnormal loading disrupts tendon repair mechanisms and contributes to degenerative changes. Furthermore, increased intra-tendinous pressure impairs capillary perfusion, thereby promoting a hypoxic microenvironment that exacerbates the inflammatory response. Dysregulated water retention due to glycosaminoglycans (GAGs) and hyaluronic acid affects intra-tendinous pressure, highlighting potential therapeutic strategies targeting ECM hydration. This review also explores the roles of macrophage polarization, cytokine regulation, and growth factors in tendon healing, emphasizing their potential therapeutic implications. By integrating the anatomical, biomechanical, and molecular insights, this review provides a comprehensive perspective of IAT pathophysiology and its healing mechanisms. Understanding these mechanisms is essential to optimizing conservative treatments, refining surgical approaches, and developing novel therapeutic strategies to enhance tendon repair and prevent disease progression.