Polydopamine Coating-Mediated Immobilization of BMP-2 on Polyethylene Terephthalate-Based Artificial Ligaments for Enhanced Bioactivity

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.

Effects of Bioactive Strontium-substituted Hydroxyapatite on Osseointegration of Polyethylene Terephthalate Artificial Ligaments

The insufficient bioactivity of polyethylene terephthalate (PET) artificial ligaments severely weakens the ligament-bone healing in anterior cruciate ligament (ACL) reconstruction, while osteogenic modification is a prevailing method to enhance osseointegration...

Posterior Ligamentous Complex Reconstruction for Cervical Dislocation and Instability in Patients without Vertebral Fracture with Artificial Ligaments: A Technical Note

Introduction: The posterior ligamentous complex (PLC) offers restraints to deformation in a complex and interconnected manner. The stability and range of motion (ROM) of the posterior cervical spine is greatly restricted when the PLC is damaged, even without bone disruptions. We describe a novel surgical technique, its advantages, and the postoperative condition of the first patient to use artificial ligament in a reconstruction surgery of PLC injuries in patients without lower cervical vertebral fracture. This technique aimed to fully retain the mobility of the injured segment based on spinal stability and apply dynamic reconstruction in patients’ treatment.Method: We present a detailed description of the reconstruction surgery with artificial ligaments performed on C4-6 PLC injuries in a 27-year-old male presented with neck pain and restricted movement following a high fall injury accompanied by impaired movement of limbs. Results: Immediately postsurgery, the patient’s neck pain and quadriparesis had been improved. The spinal canal decompression and cervical spine sequence results were satisfactory, the facet joint face was in a good position, and the spinous process spacing returned to normal. After three months of rehabilitation, the patient reported improvement of symptoms and the physical and imaging examination showed a significant improvement in the patient’s condition. The patient’s neck mobility motor function had improved further.Conclusion: The present data demonstrate that the novel technique for reconstruction of PLC injury is feasible and safe. However, familiarity with cervical anatomy and adequate experience in lateral mass screws placement during surgery is crucial for this procedure. Therefore, a highly experienced cervical surgery team is recommended to perform the surgery.

Influence of silk fibroin/sodium alginate coatings on the mineralization of silk fibroin fiber artificial ligament prototypes

The goal of the present work is to investigate the effects of varying coatings on in vitro mineralization of silk fibroin fiber artificial ligaments (SFALs). Silk fibroin (SF) and sodium alginate (SA) aqueous solutions with varying concentrations were respectively employed for coating surfaces of the SFALs to improve calcium phosphate (CaP) deposition. Scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and Energy-dispersive X-ray spectroscopy were utilized for characterizations. Furthermore, the surface of the SFAL was modified with SF/SA composite coatings. The volume ratios of the SF to the SA were set at 2:8, 4:6, 5:5, 6:4 and 8:2. The results show that either the SF or the SA coatings can improve the mineralization of the SFALs in vitro. The concentration of 1% for the SF and the SA coatings is conducive to deposit more calcium ions and obtain a biomimetic Ca/P ratio. Furthermore, the SF/SA composite coatings facilitate a thicker and uniform deposition layer than the SF and the SA coatings. The sediments are spherical particles and are more uniform in size. Therefore, the SF/SA composite coatings have more significant efficacy, particularly when the volume ratio of the SF to the SA was 4:6. The present work indicates that the SF/SA coatings possess excellent potential in promoting the osseointegration of artificial ligaments implanted in bone tunnels.

The Experience of ACL Reconstruction with Synthetics Ligament: Where are we now?

The dispute on artificial ligaments used for anterior cruciate ligament (ACL) reconstruction has been a long time issue. Admittedly, due to designing defects, materials deficient without creeping, viscoelasticity and biocompatibility, and incorrect surgical technique, early application of synthetic ligament in ACL reconstruction did not yield good outcomes. For a long time, a poor outcome occupied our consensus. Whilst the poignant lessons didn’t drive people to thoroughly figure out underlying reasons but amplified the fear of synthetics ligament in the ACL reconstruction. Recent 15 years, a new generation synthetic ligament, Ligament Advanced Reinforcement System (LARS) developed for ACL/PCL reconstruction has been widely used in China. There are at least 147 papers on LARS published in Chinese and over 47 SCI papers published in English. Consistently, a positive outcome has been concluded in most reports with an early return to sports and lower complication or failure rate. Cumulative failure rate from short- and mid-term follow-ups was only 2.6% according to Batty et al., which has been commended as “surprisingly impressive” by James H. Lubowitz of journal Arthroscopy. In China, LARS ligaments have been approved by CFDA since 2004 and been used for ACL reconstruction over 30,000 cases. Recently a national multi-centers clinical investigation has been done in long-term failure analysis of the ACLR with LARS, which has involved 20 Chinese clinical centers and 1146 cases with mean follow-up time of 87 months（7 years）, organized by the Chinese Artificial Ligament Study Group (CALSG), with an acceptable outcome in failure rate of 4.5% and complication rate of 4.1%. The following factors were concluded as main failure reasons, 1）incorrect surgical technique in a non-isometric ACL reconstruction, 2）lack of the graft biocompatibility and rigid screw interface fixation, 3) non-suitable indicated patients’ selection and rehabilitation program. Compared with reported long-term failure rate in auto（10%）or in allografts（24%）, the outcome of Synthetic ligament was more superior and acceptable results. Moreover, the functional evaluation and return to sports of the patients were also high satisfying, despite some complication, such as screw loose, remnant stimulation but very rear synovitis. Non-isometric tunnel position was the main failure reason which caused by surgeons tech. An ISOMETRIC surgical technique should be stressed especially in ACL reconstruction using synthetic, focused on surgeon education, instead of simply blaming the artificial graft. Based on the systemic review and our study, a modification of synthetic graft has been developed successfully in experiment, graft fixation, synthetics materials modified with Polyethylene Terephthalate (PET) which has facilitated the biocompatibility. Our clinical investigation has also focused on a near-isometric ACL reconstruction, which would decrease the graft tunnel motion and facilitate artificial graft successful. Non-isometric input will predispose the grafts easy failure because of over tension on the graft while joint moving. Carefully selected patients, proper surgical technique, and standard rehabilitation program will ensure artificial ligament successfully. We will keep devoting to innovate artificial ligaments, including tissue engineering, bio-mimics design, advanced fixation, hybrid graft designing and more precise Isometric surgical technique. Never forgetting our beginning mind, the artificial ligaments will open a new epoch in the future of ACL reconstruction.

Foreign Body Reaction Associated With Artificial LARS Ligaments: A Retrieval Study

Background: Artificial ligaments have been developed and used in the treatment of ligamentous injuries since the 1970s. The early generation of artificial ligaments showed promising short-term results but resulted in high rates of rupture and inflammatory reaction in the surrounding tissues. Purpose: To determine whether the use of Ligament Augmentation and Reconstruction System (LARS) ligaments is associated with the development of intra-articular foreign body reaction. Study Design: Case series; Level of evidence, 4. Methods: LARS ligaments were explanted from 15 patients under 6 consultant orthopaedic surgeons at 8 surgical centers. Of these, 14 explanted samples were sent for macroscopic and histological analysis, with the 1 remaining sample sent for scanning electron microscopy, to assess for inflammatory change as well as the degree of fibrous tissue ingrowth. Results: We observed a foreign body reaction in 10 of 14 explanted LARS ligaments. Seven samples demonstrated fibrous tissue ingrowth, with 5 producing only focal or incomplete ingrowth. The 2 samples with extensive fibrous coverage were completely free of any foreign body reaction, while all 5 remaining samples with only focal or partial fibrous ingrowth were associated with at least some degree of harmful immune response. Conclusion: The LARS ligament is still associated with a clinically significant degree of foreign body reaction despite the LARS Company’s efforts to reduce complications through improved design. The development and completion of fibrous tissue ingrowth may work to reduce the occurrence of a foreign body reaction.

A Novel Surgical Technique for Fixation of Recurrent Acromioclavicular Dislocations: AC Dog Bone Technique in Combination with Autogenous Semitendinosus Tendon Graft

Various surgical techniques have been described for the fixation of acromioclavicular (AC) dislocations. However, recurrent dislocation is one of the main complications associated with the majority of these techniques. We report a case of postoperative AC joint redislocation. In order to overcome recurrent dislocation after revision surgery, a reconstruction of the conoid and trapezoid ligament with the use of a free tendon graft in combination with a FiberTape was provided within a novel surgical technique. After 12 months, the patient was very satisfied with the functional outcome. The patient achieved excellent results in the Constant (98 points), SPADI (0 points), and QuickDASH score (0 points). The described technique results in an anatomic reconstruction of the AC joint. The nonrigid nature of the intervention seems to restore the normal arthrokinematics by reconstructing the coracoclavicular ligaments with an autograft which is then protected by the AC Dog Bone artificial ligaments during the healing period. The arthroscopic approach to the AC joint with minimal exposure reduces the risks and complications of the intervention. This is the first case in literature that utilizes the artificial dog bone ligament securing the autograft in an anatomic AC reconstruction.