BMP-2 gene-modified mesenchymal stem cells enhance tendon–bone healing in ACL reconstruction: a rabbit micro-CT and biomechanical study

Abstract

Objective: Suboptimal tendon-bone interface healing remains a critical challenge affecting outcomes of anterior cruciate ligament (ACL) reconstruction. This study investigates whether BMP-2 gene-modified bone marrow mesenchymal stem cells (MSCs) enhances tendon-bone osseointegration. Methods: An ACL reconstruction model was established in 18 New Zealand white rabbits, randomized into three groups: Control(fibrin glue), MSCs-Ad (adenovirus-vector transfected MSCs), MSCs-BMP2 (BMP-2-overexpressing MSCs). Micro-CT analysis and biomechanical testing assessed bone regeneration and interface properties at 4 weeks postoperatively. Results: Micro-CT analysis revealed a significant enhancement in bone regeneration within the tunnel in the order of MSCs-BMP2 > MSCs-Ad > Control. The MSCs-BMP2 group demonstrated the highest values for bone volume fraction (BV/TV: 0.35 ± 0.05 vs. 0.27 ± 0.03 in MSCs-Ad vs. 0.22 ± 0.03 in Control), trabecular number (Tb.N: 0.73 ± 0.01 vs. 0.68 ± 0.01 vs. 0.64 ± 0.03), and trabecular thickness (Tb.Th: 0.46 ± 0.02 vs. 0.38 ± 0.01 vs. 0.36 ± 0.03). Biomechanical testing yielded consistent results: the maximum failure load for the MSCs-BMP2 group (32.80 ± 3.94 N) was significantly greater than that of both the MSCs-Ad (27.37 ± 2.15 N) and control (21.07 ± 1.94 N) groups, while the MSCs-Ad group also showed a significant improvement over the control. Conclusion: BMP-2 gene-modified MSCs synergistically accelerate tendon-bone osseointegration, providing a theoretical foundation for biological augmentation in ACL reconstruction. This strategy may reduce postoperative graft failure risks. Future studies should validate clinical translation through long-term monitoring and mechanistic investigations.