Tendon-to-Bone Healing in a Rat Extra-articular Bone Tunnel Model: A Comparison of Fresh Autologous Bone Marrow and Bone Marrow-Derived Mesenchymal Stem Cells

Am J Sports Med. 2019 Sep;47(11):2729-2736. doi: 10.1177/0363546519862284. Epub 2019 Jul 24.

Abstract

Background: Despite widespread acceptance of fresh autologous bone marrow (BM) for use in clinical practice, limited information exists to analyze if tendon-to-bone healing could be accelerated with local use of fresh autologous BM.

Purpose: To investigate the effect of fresh autologous BM on tendon-to-bone healing with a novel rat model.

Study design: Controlled laboratory study.

Methods: An extra-articular bone tunnel was created and filled with an autologous tendon graft in skeletally mature Sprague-Dawley rats (N = 60). They were then randomly divided into 3 groups: BM group (injection of fresh autologous BM into the tendon-bone interface, n = 20), BM-derived mesenchymal stem cell (BMSC) group (injection of allogenic cultured BMSCs, n = 20), and the control group (tendon-bone interface without injection of BM or BMSCs, n = 20). Biomechanical, histological, and immunohistochemical analyses were performed at 2 and 6 weeks after surgery.

Results: The BM group showed a relatively well-organized and dense connective tissue interface with better orientation of collagen fibers as compared with the BMSC group. At 2 weeks, the tendon-bone interface tissue thickness of the BMSC group was 140 ± 25 μm (mean ± SEM), which was significantly greater than the BM group (58 ± 15 μm). The BM group showed fewer M1 macrophages at the tendon-bone interface at 2 and 6 weeks (P < .001). In contrast, there were more M2 macrophages at the interface in the BM group 2 and 6 weeks postoperatively when compared with controls and the BMSC group (P < .001). Biomechanical tests revealed significantly higher stiffness in the BM group versus the control and BMSC groups at 2 and 6 weeks after surgery (P < .05). Load to failure showed similar trends to stiffness.

Conclusion: These findings indicate that local delivery of fresh autologous BM enhances tendon-to-bone healing better than the alternative treatments in this study. This effect may be partially due to the observed modulation of inflammatory processes, especially in M2 macrophage polarization.

Clinical relevance: Fresh autologous BM could be a treatment option for this disorder.

Keywords: bone marrow; bone marrow–derived mesenchymal stem cells; macrophage; tendon-to-bone healing.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Transplantation*
  • Bone and Bones / physiology
  • Bone and Bones / surgery*
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Models, Animal
  • Random Allocation
  • Rats, Sprague-Dawley
  • Tendons / physiology
  • Tendons / transplantation*
  • Transplantation, Autologous
  • Wound Healing / physiology*