Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea.
Stem Cell and Regenerative Medicine Research Institute, Samsung Medical Center, Seoul, Republic of Korea.
Am J Sports Med. 2021 May;49(6):1538-1550. doi: 10.1177/0363546521998021. Epub 2021 Mar 25.
Meniscal deficiency from meniscectomy is a common situation in clinical practices. Regeneration of the deficient meniscal portion, however, is still not feasible.
To develop an injectable hydrogel system consisting of fibrin (Fb) and polyethylene oxide (PEO) and to estimate its clinical potential for treating a segmental defect of the meniscus in a rabbit meniscal defect model.
Controlled laboratory study.
The Fb/PEO hydrogel was fabricated by extruding 100 mg·mL of fibrinogen solution and 2,500 U·mL of thrombin solution containing 100 mg·mL of PEO through a dual-syringe system. The hydrogels were characterized by rheological analysis and biodegradation tests. The meniscal defects of New Zealand White male rabbits were generated by removing 60% of the medial meniscus from the anterior side. The removed portion included the central portion. The Fb/PEO hydrogel was injected into the meniscal defect of the experimental knee through the joint space between the femoral condyle and tibial plateau at the anterior knee without a skin incision. The entire medial menisci from both knees of each rabbit were collected and photographed before placement in formalin for histological processing. Hematoxylin and eosin, safranin O, and immunohistochemical staining for type II collagen was performed. The biomechanical property of the regenerated meniscus was evaluated using a universal tensile machine.
The Fb/PEO hydrogel was fabricated by an in situ gelation process, and the hydrogel displayed a semi-interpenetrating polymer network structure. We demonstrated that the mechanical properties of Fb-based hydrogels increased in a PEO-dependent manner. Furthermore, the addition of PEO delayed the biodegradation of the hydrogel. Our in vivo data demonstrated that, as compared with Fb hydrogel, Fb/PEO hydrogel injection into the meniscectomy model showed improved tissue regeneration. The regenerated meniscal tissue by Fb/PEO hydrogel showed enhanced tissue quality, which was supported by the histological and biomechanical properties.
The Fb/PEO hydrogel had an effective tissue-regenerative ability through injection into the in vivo rabbit meniscal defect model.
This injectable hydrogel system can promote meniscal repair and be readily utilized in clinical application.
半月板切除术后的半月板缺失是临床常见情况,但半月板部分的再生仍然不可行。
开发一种由纤维蛋白(Fb)和聚氧化乙烯(PEO)组成的可注射水凝胶系统,并评估其在兔半月板缺损模型中治疗半月板节段性缺损的临床潜力。
对照实验室研究。
通过从双注射器系统中挤出 100mg·mL 的纤维蛋白原溶液和 2500U·mL 的含 100mg·mL 的 PEO 的凝血酶溶液来制备 Fb/PEO 水凝胶。通过流变分析和生物降解试验对水凝胶进行了表征。通过从前侧切除内侧半月板的 60%来生成新西兰白兔的半月板缺损。切除的部分包括中央部分。通过在前膝关节处股骨髁和胫骨平台之间的关节间隙将 Fb/PEO 水凝胶注入实验膝关节的半月板缺损中,无需皮肤切口。在将整个内侧半月板放入福尔马林进行组织学处理之前,从每个兔子的双侧膝关节收集并拍照。进行苏木精和伊红、番红 O 以及 II 型胶原的免疫组织化学染色。使用万能拉伸机评估再生半月板的生物力学性能。
Fb/PEO 水凝胶通过原位凝胶化过程制备,水凝胶显示出半互穿聚合物网络结构。我们证明,基于 Fb 的水凝胶的机械性能以 PEO 依赖的方式增加。此外,PEO 的添加延迟了水凝胶的生物降解。我们的体内数据表明,与 Fb 水凝胶相比,将 Fb/PEO 水凝胶注入半月板切除术模型可改善组织再生。Fb/PEO 水凝胶再生的半月板组织显示出增强的组织质量,这得到了组织学和生物力学特性的支持。
Fb/PEO 水凝胶通过注射到体内兔半月板缺损模型中具有有效的组织再生能力。
这种可注射水凝胶系统可促进半月板修复,易于在临床应用中使用。