Comparative Analysis of Tendon Healing in a Clinically Relevant Mouse Model of Achilles Tendon Repair

Area of Science:

• Biomedical Engineering
• Regenerative Medicine
• Orthopedic Research

Background:

• Adult tendon injuries present significant clinical challenges due to limited natural healing capacity.
• The mouse model is crucial for studying tendon healing mechanisms and evaluating new therapies, but injury models lack standardization.
• Comparisons between reconstructive and non-reconstructive tendon injury models are scarce.

Purpose of the Study:

• To compare the functional, cellular, and molecular outcomes of three distinct Achilles tendon injury models in mice.
• To evaluate the impact of surgical repair versus non-reconstructive approaches on tendon healing.
• To inform the selection of appropriate mouse models for future tendon research.

Main Methods:

• Three clinically relevant Achilles tendon injury models were established: tenotomy-only, tenotomy with cast immobilization, and tenotomy with microsurgical repair and immobilization.
• Functional recovery was assessed, alongside cellular analysis (macrophage recruitment, Scleraxis-lineage tenocyte tracing) and gene expression profiling (tenogenic and fibrotic markers).

Main Results:

• Microsurgical repair led to superior functional recovery compared to non-reconstructive models.
• Surgical repair was associated with reduced inflammatory macrophage infiltration and decreased fibrotic gene expression.
• Enhanced tenogenic gene expression and increased recruitment of Scleraxis-lineage tenocytes were observed following surgical repair.

Conclusions:

• Surgical repair significantly enhances functional, cellular, and molecular aspects of Achilles tendon healing in a mouse model.
• The choice of injury model, particularly the inclusion of surgical repair, profoundly influences healing outcomes.
• These findings highlight critical differences in healing responses and provide guidance for selecting optimal experimental models in tendon research.