Decellularization-Based Modification Strategy for Bioactive Xenografts Promoting Tendon Repair

Area of Science:

• Biomaterials Science
• Immunology
• Regenerative Medicine

Background:

• Xenografts are promising for tendon repair but face immunogenicity challenges due to extracellular matrix components.
• Decellularization alone does not fully eliminate xenograft immunogenicity, necessitating further strategies.

Purpose of the Study:

• To develop a post-decellularization modification strategy using a human-derived rosiglitazone-loaded decellularized extracellular matrix (R-dECM).
• To assess R-dECM's ability to mask antigenic epitopes, preserve cell function, and reduce immunogenicity for enhanced tendon repair.

Main Methods:

• Developed human-derived R-dECM releasing rosiglitazone for over 7 days.
• Investigated R-dECM's effects on macrophage polarization (M1 suppression, M2 stabilization) and tendon-derived stem cell (TDSC) functions in vitro.
• Utilized RNA sequencing to analyze cell crosstalk.
• Evaluated R-dECM in a rat patellar tendon defect model.

Main Results:

• R-dECM suppressed M1 macrophage polarization and stabilized M2 macrophages in vitro.
• Protected TDSC migration and collagen synthesis while mitigating detrimental cell crosstalk.
• Effectively inhibited early inflammation and prevented chronic inflammation in vivo.
• Demonstrated superior tendon repair outcomes compared to decellularized extracellular matrix (dECM).

Conclusions:

• The proposed R-dECM strategy establishes immune evasion, enhancing xenograft efficacy.
• R-dECM shows significant potential for improving long-term clinical outcomes in xenogeneic tendon grafting.
• This novel bioactive scaffold offers a promising approach for severe tendon defect treatment.