Abstract
Background/objectives: Polyethylene terephthalate (PET)-based artificial ligaments are one of the most commonly used grafts in anterior cruciate ligament (ACL) reconstruction surgery. However, the lack of favorable hydrophilicity and cell attachment for PET highly impeded its widespread application in clinical practice. Studies found that surface modification on PET materials could enhance the biocompatibility and bioactivity of PET ligaments. In this study, we immobilized bone morphogenetic protein-2 (BMP-2) on the surface of PET ligaments mediated by polydopamine (PDA) coating and investigated the bioactivation and graft-to-bone healing effect of the modified grafts in vivo and in vitro. Methods: In this study, we prepared the PDA coating and subsequent BMP-2-immobilized PET artificial ligaments. Scanning electron microscopy (SEM) was used to analyze the morphological changes of the modified grafts. In addition, the surface wettability properties of the modified ligaments, amount of immobilized BMP 2, and the release of BMP-2 during a dynamic period up to 28 days were tested. Then, the attachment and proliferation of rat bone mesenchymal stem cells (rBMSCs) on grafts were examined by SEM and Cell Counting Kit-8 (CCK-8) assay, respectively. Alkaline phosphatase (ALP) assay, RT-PCR, and Alizarin Red S staining were performed to test the osteoinduction property. For in vivo experiments, an extra-articular graft-to-bone healing model in rabbits was established. At 8 weeks after surgery, biomechanical tests, micro-CT, and histological staining were performed on harvested samples. Results: A surface morphological analysis verified the success of the PDA coating. The wettability of the PET artificial ligaments was improved, and more than 80% of BMP-2 stably remained on the graft surface for 28 days. The modified grafts could significantly enhance the proliferation, attachment, as well as expression of ALP and osteogenic-related genes, which demonstrated the favorable bioactivity of the grafts immobilized with BMP-2 in vitro. Moreover, the grafts immobilized with BMP-2 at a concentration of 138.4 ± 10.6 ng/cm2 could highly improve the biomechanical properties, bone regeneration, and healing between grafts and host bone after the implantation into the rabbits compared with the PDA-PET group or the PET group. Conclusion: The immobilization of BMP-2 mediated by polydopamine coating on PET artificial ligament surface could enhance the compatibility and bioactivity of the scaffolds and the graft-to-bone healing in vivo.
Highlights
Anterior cruciate ligament (ACL) injury, which may result in knee instability, secondary cartilage damage, and osteoarthritis (Shelbourne and Gray, 2000; Lohmander et al, 2007; Lidén et al, 2008), is a common injury among young adults and athletes (Zantop et al, 2008; Sofu et al, 2015)
We examined the morphology of polyethylene terephthalate (PET), PDA-PET, 250B-PDAPET, and 500B-PDA-PET samples via SEM
The 250B-PDA-PET (Figure 1 C1, C2) and 500B-PDA-PET (Figure 1 D1, D2) showed a coating with fewer particles than that on the PET group, and the layer modified by BMP-2 seemed thicker than the PDA layer in some areas
Summary
Anterior cruciate ligament (ACL) injury, which may result in knee instability, secondary cartilage damage, and osteoarthritis (Shelbourne and Gray, 2000; Lohmander et al, 2007; Lidén et al, 2008), is a common injury among young adults and athletes (Zantop et al, 2008; Sofu et al, 2015). Allograft tendon, or artificial ligaments are available grafts for ACL reconstruction. Compared with allografts or autografts, artificial ligaments can meet the demand of stability and flexibility of knee joints, such as tension, flexion, and torsion (Huang et al, 2012; McDonald et al, 2021), and overcome the drawbacks of donor site morbidity and reduce the incidence of disease transmission (Vaishya et al, 2015; Jia et al, 2017). Surface modification was introduced to improve the bioactivity of PET ligaments
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