Optimal timing of bone marrow aspiration concentrate injection for tendon-bone healing in a chronic rat rotator cuff tear model.

Background: The Bone marrow aspirate concentrate (BMAC) injection is a beneficial therapy for bone-tendon interface (BTI) regeneration following rotator cuff (RC) repair. However, the optimal timing for BMAC injection remains undetermined. Injection at different timepoints may influence BTI regeneration.

Methods: After concentrating bone marrow (BM) to obtain BMAC, the viability of cells, nucleated cell content, platelet count, stem cell number, and concentration of growth factors in both BM and BMAC were comparatively evaluated. Supraspinatus tendon tears were induced at the greater tuberosity in 152 Wistar rats. Three weeks after the tear induction, the rats following RC repair surgery were then randomly divided into four groups based on the timing of BMAC injection: PBS injected immediately during RC repair (PBS group), BMAC injected immediately (P0-BMAC group), on postoperative day 7 (P7-BMAC group), or day 14 (P14-BMAC group). Eight weeks after RC repair, the supraspinatus tendon-proximal humerus complexes were harvested for evaluating BTI regeneration using micro-CT, histological and biomechanical testing. Additionally, at the day 0, 3, 10, 17 after RC repair, the specimens were harvested for evaluating the inflammation and oxidative stress.

Results: Cell viability in the BMAC exceeded 90%. The BMAC contained higher concentrations of platelets, nucleated cells, stem cells, TGFβ1, and IGF1 compared to BM. In vivo results demonstrated that the BMAC injection on postoperative day 7 had a more pronounced effect on BTI regeneration compared to other timepoints. Micro-CT analysis revealed that the new bone in the P7-BMAC group formed and remodelled significantly better than in the P14-BMAC, P0-BMAC, or PBS groups. Histologically, the P7-BMAC group exhibited a significantly higher rate of fibrocartilage regeneration at the RC healing site compared to the P14-BMAC, P0-BMAC, or PBS groups. Biomechanically, the P7-BMAC group showed significantly higher failure load and stiffness compared to the P14-BMAC, P0-BMAC, or PBS groups. Moreover, the P7-BMAC group showed significantly inhibiting inflammation and decreasing oxidative stress in the ST-proximal humerus complexes as compared with the other groups.

Conclusions: BMAC injected at 7 days postoperatively is an optimal timing of the BMAC Injection for BTI regeneration in a chronic rat RCT model.