Mao-dan Nie , Bing-kun Bao , Ning-ze Zhang , Rong-shan Cheng , Ling-jie Fu , Cheng-Kung Cheng
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引用次数: 0
Abstract
Background
Intervertebral disc (IVD) herniation is a degenerative spine disease, and current treatments often result in reherniation due to iatrogenic annulus fibrosus (AF) defects. Developing effective AF repair strategies is critical to preventing reherniation and improving surgical outcomes. This study aims to develop a novel hydrogel plug to repair significant AF defects, improving surgical outcomes and reducing the risk of reherniation.
Methods
Inspired by Dumbbell, a novel hydrogel plug was developed using methacrylate-grafted hyaluronic acid and 4-arm polyethylene glycol. The plug's geometry was optimized via an IVD finite element (FE) model, adjusting the bulbous end's thickness, radius, and curvature. A scanning electron microscope characterized the hydrogel's microstructure. Swelling behavior was assessed through freeze-drying and rehydration, and the mechanical properties were evaluated by compression and tensile testing. Degradation studies were performed in vitro and in vivo. The material's biocompatibility was assessed with cytotoxicity assays and subcutaneous implantation in mice. The repair efficacy of the dumbbell-shaped plug was analyzed using the lumbar spine FE model and was validated through dynamic mechanical testing. Finally, the plugs were inserted into the goat IVD injury model to compare the repair effects with the goat model for non-damaged, non-repaired, and suture-repaired conditions. The harvested samples were assessed using MRI and histological analysis, and the stability of the repair was verified through mechanical testing.
Results
The hydrogel exhibited rapid swelling, had mechanical properties similar to the natural AF, showed a stable degradation profile, and had excellent biocompatibility. For repairing a 3 mm defect, the FE simulation showed that a plug with an inner bulbous end radius of 2.25 mm, a thickness of 1.5 mm, and a curvature of 20–30° provided the most uniform stress distribution and optimal lumbar stability. The plug was successfully implanted into an ex vivo lumbar model and maintained its position after 10,000 cyclic loads. In the vivo goat model, no marked degeneration of the plug is observed on MRI after 4 weeks. Histological and immunostaining results revealed no significant inflammation, with slight vascular and fibrous tissue formation in both the plug and suture groups. The plug group demonstrated superior compressive strength compared to the suture repair and the untreated group.
Conclusion
This study developed and tested a novel hydrogel plug system for repairing large AF defects. The hydrogel plug resulted in an AF repair with superior mechanical properties, better biocompatibility, and a more effective defect repair than traditional suturing.
The translational potential of this article
Given the current lack of products for repairing significant AF defects, this study developed a novel hydrogel plug system with excellent mechanical properties and biocompatibility, resulting in an effective AF repair. This implant has substantial translational potential for clinical applications in minimally invasive spinal surgeries to address significant AF defects.
期刊介绍:
The Journal of Orthopaedic Translation (JOT) is the official peer-reviewed, open access journal of the Chinese Speaking Orthopaedic Society (CSOS) and the International Chinese Musculoskeletal Research Society (ICMRS). It is published quarterly, in January, April, July and October, by Elsevier.