Abstract
PurposeThe effect of bone marrow mesenchymal stromal cells (BMSCs) and platelet-rich plasma (PRP) on tendon allograft maturation in a large animal anterior cruciate ligament (ACL) reconstruction model was reported for the first time. It was hypothesised that compared with non-augmented ACL reconstruction, BMSCs and PRP would enhance graft maturation after 12 weeks and this would be detected using magnetic resonance imaging (MRI).MethodsFifteen sheep underwent unilateral tendon allograft ACL reconstruction using aperture fixation and were randomised into three groups (n = 5). Group 1 received 10 million allogeneic BMSCs in 2 ml fibrin sealant; Group 2 received 12 ml PRP in a plasma clot injected into the graft and bone tunnels; and Group 3 (control) received no adjunctive treatment. At autopsy at 12 weeks, a graft maturation score was determined by the sum for graft integrity, synovial coverage and vascularisation, graft thickness and apparent tension, and synovial sealing at tunnel apertures. MRI analysis (n = 2 animals per group) of the signal–noise quotient (SNQ) and fibrous interzone (FIZ) was used to evaluate intra-articular graft maturation and tendon–bone healing, respectively. Spearman’s rank correlation coefficient (r) of SNQ, autopsy graft maturation score and bone tunnel diameter were analysed.ResultsThe BMSC group (p = 0.01) and PRP group (p = 0.03) had a significantly higher graft maturation score compared with the control group. The BMSC group scored significantly higher for synovial sealing at tunnel apertures (p = 0.03) compared with the control group. The graft maturation score at autopsy significantly correlated with the SNQ (r = − 0.83, p < 0.01). The tunnel diameter of the femoral tunnel at the aperture (r = 0.883, p = 0.03) and mid-portion (r = 0.941, p = 0.02) positively correlated with the SNQ.ConclusionsBMSCs and PRP significantly enhanced graft maturation, which indicates that orthobiologics can accelerate the biologic events in tendon allograft incorporation. Femoral tunnel expansion significantly correlated with inferior maturation of the intra-articular graft. The clinical relevance of this study is that BMSCs and PRP enhance allograft healing in a translational model, and biological modulation of graft healing can be evaluated non-invasively using MRI.
Highlights
Materials and methodsGraft healing after anterior cruciate ligament (ACL) reconstruction consists of tendon–bone healing and matrix remodelling (“ligamentisation”) of the intra-articular graft [13, 15]
The purpose of this study was to compare the effect of Bone marrow mesenchymal stromal cells (BMSCs) and Platelet-rich plasma (PRP) on tendon allograft maturation in a large animal model, and to determine if magnetic resonance imaging (MRI) can be used to identify biological modulation of graft healing
The manner by which BMSCs exert their effect on graft healing remains unknown, and future studies that tracks the cells after implantation will help reveal the mechanism
Summary
Graft healing after ACL reconstruction consists of tendon–bone healing and matrix remodelling (“ligamentisation”) of the intra-articular graft [13, 15]. Graft remodeling can be measured non-invasively using MRI by measuring signal intensity of the intra-articular graft (signal–noise quotient, SNQ) [7]. Healing at the tendon–bone interface can be evaluated at fibrous interzone (FIZ) on MRI [13]. Mesenchymal stromal cells (MSCs) can enhance tissue regeneration by differentiation, paracrine effects, or via immunomodulatory activity [1]. Bone marrow mesenchymal stromal cells (BMSCs) [12, 22] and PRP [24] have shown positive effects on graft healing in small animals. Evaluation in a large animal is an important translational step because it permits human-sized grafts and fixation systems to be used [16]
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