Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota, USA.
GEMpath, Inc., Longmont, Colorado, USA.
J Orthop Res. 2022 Feb;40(2):323-337. doi: 10.1002/jor.25054. Epub 2021 May 16.
Experimental analyses of posttraumatic knee arthrofibrosis utilize a rabbit model as a gold standard. However, a rodent model of arthrofibrosis offers many advantages including reduced cost and comparison with other models of organ fibrosis. This study aimed to characterize the biomechanical, histological, and molecular features of a novel posttraumatic model of arthrofibrosis in rats. Forty eight rats were divided into two equal groups. An immobilization procedure was performed on the right hind limbs of experimental rats. One group was immobilized for 4 weeks and the other for 8 weeks. Both groups were remobilized for 4 weeks. Limbs were studied biomechanically via assessment of torque versus degree of extension, histologically via whole knee specimen, and molecularly via gene expression of posterior capsular tissues. Significant differences were observed between experimental and control limbs at 4 N-cm of torque in the 4-week (knee extension: 115° ± 8° vs. 169° ± 17°, respectively; p = 0.007) and 8-week immobilization groups (knee extension: 99° ± 12° vs. 174° ± 9°, respectively; p = 0.008). Histologically, in each group experimental limbs demonstrated increased posterior capsular thickness and total area of tissue when compared to control limbs (p < 0.05). Gene expression values evaluated in each group were comparable. This study presents a novel rat model of arthrofibrosis with severe and persistent knee contractures demonstrated biomechanically and histologically. Statement of clinical significance: Arthrofibrosis is a common complication following contemporary total knee arthroplasties. The proposed model is reproducible, cost-effective, and can be employed for translational investigations studying the pathogenesis of arthrofibrosis and efficacy of neoadjuvant pharmacologic agents.
实验性创伤后膝关节关节纤维化分析采用兔模型作为金标准。然而,关节纤维化的啮齿动物模型具有许多优势,包括降低成本和与其他器官纤维化模型进行比较。本研究旨在描述一种新型创伤后大鼠关节纤维化模型的生物力学、组织学和分子特征。48 只大鼠被分为两组。实验组的右后肢进行固定。一组固定 4 周,另一组固定 8 周。两组均进行 4 周的再活动。通过评估扭矩与伸展度的关系来对肢体进行生物力学研究,通过整个膝关节标本进行组织学研究,通过后囊组织的基因表达进行分子学研究。在 4 周(膝关节伸展:115°±8° vs. 169°±17°,分别为 4 N-cm 扭矩;p=0.007)和 8 周固定组(膝关节伸展:99°±12° vs. 174°±9°,分别为 4 N-cm 扭矩;p=0.008)中,实验组与对照组肢体之间存在显著差异。在每组中,与对照组肢体相比,实验组肢体的后囊厚度和组织总面积均增加(p<0.05)。每组评估的基因表达值相似。本研究提出了一种新型的大鼠关节纤维化模型,具有生物力学和组织学上严重且持续的膝关节挛缩。临床意义声明:关节纤维化是现代全膝关节置换术后的常见并发症。所提出的模型具有可重复性、成本效益高,并可用于研究关节纤维化发病机制和新辅助药物疗效的转化研究。