The effect of demineralised bone matrix, bone marrow mesenchymal stromal cells and platelet-rich plasma on bone tunnel healing after anterior cruciate ligament reconstruction: a comparative micro-computed tomography study in a tendon allograft sheep model

Adam T Hexter, Aikaterina Karali, Alex Kao, Gianluca Tozzi, Nima Heidari, Aviva Petrie, Ashleigh Boyd, Deepak M Kalaskar, Catherine Jane Pendegrass, Scott A. Rodeo, Fares S. Haddad, Gordon William Blunn

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The effect of demineralised bone matrix (DBM), bone marrow-derived mesenchymal stromal cells (BMSCs) and platelet-rich plasma (PRP) on bone tunnel healing in anterior cruciate ligament (ACL) reconstruction has not been comparatively assessed.

Hypothesis: These orthobiologics will reduce tunnel widening and the effects on tunnel diameter will correlate with tunnel wall sclerosis.
Study design: Controlled laboratory study.

Methods: 20 sheep underwent unilateral ACL reconstruction using tendon allograft and outside-in interference screw fixation. The animals were randomised into 4 groups (n=5 animals per group). Group 1 received 5 ml DBM paste; Group 2 received 10 million BMSCs in fibrin sealant; Group 3 received 12 ml activated leucocyte-poor PRP; and Group 4 (control) received no treatment. The sheep were euthanised after 12 weeks and micro-computed tomography (µCT) scans performed. The femoral and tibial tunnel was divided into thirds (aperture, mid-portion and exit) and the trabecular bone structure, bone mineral density (BMD), and tunnel diameter were measured. Tunnel sclerosis was defined by a higher bone volume in a 250 µm volume of interest (VOI) compared to a 4 mm VOI surrounding the tunnel.

Results: Compared with the control group, the DBM group had a significantly higher bone volume fraction (52.7 % versus 31.8 %, p=0.020) and BMD (0.55 g/cm3 versus 0.47 g/cm3, p=0.031) at the femoral aperture and significantly higher bone volume fraction at femoral mid-portion (44.2 % versus 32.9 %, p=0.038). No significant differences were seen between the PRP and BMSC groups and the control group in terms of trabecular bone analysis and BMD. In the control group, widening at the femoral tunnel aperture was significantly higher than at the mid-portion (46.7 mm2 versus 41.7 mm2 %, p=0.034). Sclerosis of the tunnel was common and most often seen at the femoral aperture. In the mid-portion of the femoral tunnel, bone volume fraction (r=0.52, p=0.019) and trabecular number positively correlated with tunnel widening (rs=0.50 , p=0.024).

Conclusions:
Only DBM led to a significant increase in bone volume, which was seen in the femoral tunnel aperture and mid-portion. No treatment significantly reduced bone tunnel widening. Tunnel sclerosis in the femoral tunnel mid-portion correlated significantly with tunnel widening.

Clinical relevance: DBM might have potential clinical use to enhance healing in the femoral tunnel after ACL reconstruction.  
 
What is known about the subject: In a rodent ACL reconstruction model, DBM treatment led to significantly higher bone volume fraction, trabecular thickness and BMD compared to an untreated control. In a rabbit ACL reconstruction model, umbilical cord blood–derived mesenchymal stem cells led to significantly reduced tunnel widening compared to an untreated control.

What this study adds to existing knowledge: This is the first large animal study using contemporary fixation methods comparing µCT findings for bone adjacent to ACL bone tunnels that have been treated with orthobiologics. A strength of this study is the comprehensive analysis of both femoral and tibial tunnels, and for the first time, analysis of different volumes of interest to clarify spatial changes and examine for tunnel sclerosis.
Original languageEnglish
JournalOrthopaedic Journal of Sports Medicine
Publication statusAccepted for publication - 29 Apr 2021

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