Mesenchymal stromal cells and platelet-rich plasma promote tendon allograft healing in ovine anterior cruciate ligament reconstruction

Abstract

Purpose The 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). Methods Fifteen 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. Results The 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. Conclusions BMSCs 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.

Infrapatellar Fat Pad Mesenchymal Stromal Cell–Derived Exosomes Accelerate Tendon-Bone Healing and Intra-articular Graft Remodeling After Anterior Cruciate Ligament Reconstruction

“…19,41 Graft healing after ACLR consists of 2 main biological processes: tendon-bone healing and intra-articular graft remodeling. 25,41,49,52 An understanding of these 2…”

Anterior Cruciate Ligament Reconstruction: Is Biological Augmentation Beneficial?

“…In the sheep model described by Hexter et al in 2020, the authors observed that BMSCs and PRP significantly enhanced graft maturation, indicating that orthobiologics might accelerate biological events related to tendon allograft incorporation [72]. They also found that femoral tunnel expansion was significantly correlated with inferior maturation of the intra-articular graft.…”

“…It is important to highlight the discrepancy between 2 recent articles: one on an experimental study stating that orthobiologics can accelerate biological events related to tendon allograft incorporation [72] and another on a clinical study on meniscal repair in the ACLR setting stating that the added use of intraoperative PRP does not improve the analyzed parameters (self-reported knee function, functional performance, and time to return to previous activity). According to Hexter et al, the use of PRP might have negative consequences for the postoperative recovery of knee range of motion [18].…”

“…A recently published study on a sheep model of ACLR has once again demonstrated that BMSCs and PRP significantly improve graft maturation [72]. Although 75% of clinical studies on BA have evaluated the efficacy of PRP, evidence demonstrating this efficacy is lacking.…”

Effects of Platelet-Rich Plasma on Clinical Outcomes After Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-analysis

“…[5][6][7][8][9]16,30,37 PRP has had great success in accelerating ACL healing in animal models. 3,10 However, clinical studies using human participants to investigate the effects of PRP on ACLR have shown inconsistent clinical outcomes. Mahdi and Hatem 16 reported that PRP was a safe procedure that enhanced graft-bone integration at 12 weeks' follow-up after ACLR.…”