Efficacy of Human Tendon-Derived Extracellular Matrix in Achilles Tendon Regeneration

Background/Objectives: Achilles tendon injuries exhibit slow and incomplete healing due to limited vascularity, cellularity, and a complex extracellular matrix (ECM). Biologically derived ECM-based therapies have emerged as promising strategies to enhance tendon repair by providing native biochemical cues. In this study, the efficacy of injectable human tendon-derived ECM (hT-ECM) was investigated using a rat Achilles tenotomy model. Methods: Percutaneous tenotomy of the right Achilles tendon in 50 rats was performed. The animals were subjected to either no treatment as a control group (CON) or hT-ECM treatment group (ECM). Tendon healing was evaluated at 1 and 6 weeks using biomechanical, histological, transmission electron microscopy, Western blot, and immunohistochemical analysis. Results: At 6 weeks, the ECM group exhibited higher load to failure (54.5 ± 15.0 N) than the CON group (28.6 ± 13.7 N) (p < 0.05). Histological evaluation revealed progressive restoration of the injured tendon in both groups over the healing period, with comparable results observed between the groups. Ultrastructural analysis revealed that the ECM group exhibited significantly increased collagen fibrils diameters (74.1 ± 19.1 nm) than the CON group (53.8 ± 13.8 nm) (p < 0.001). Western blot exhibited that collagen I (COL I) expression at 6 weeks was significantly higher in the ECM group compared with the CON group (p < 0.05). Conclusions: These outcomes suggest that injectable hT-ECM improves early repair responses in a rat Achilles tenotomy model. Molecular analyses suggested that the therapeutic effects of hT-ECM injection could be linked to enhanced collagen type I production. Based on the study, hT-ECM injection might be a good adjuvant option for the treatment of Achilles tendon injuries.