Establishment of anterior cruciate ligament reconstruction model in cynomolgus monkey with autogenous hamstring tendon transplantation_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

LU Xiaojun ¹ , YU Yang ¹ , XIE Bing ² , WANG Guoliang ¹ , YANG Tengyun ¹ , XIONG Bohan ¹ , LIU Jinrui ¹ ,  LI Yanlin ¹

1. Department of Sports Medicine, First Affiliated Hospital of Kunming Medical University, Kunming Yunnan, 650032, P. R. China;
2. Department of Obstetrics, First Affiliated Hospital of Kunming Medical University, Kunming Yunnan, 650032, P. R. China;

Corresponding author：

LI Yanlin, Email: 852387873@qq.com

Keywords：

Animal model; cynomolgus monkey; anterior cruciate ligament reconstruction; autologous tendon transplantation; hamstring tendon

DOI：

10.7507/1002-1892.202303103

Video：

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Objective To investigate the feasibility of establishing an anterior cruciate ligament (ACL) reconstruction model using hamstring tendon autograft in cynomolgus monkeys. Methods Twelve healthy adult male cynomolgus monkeys, weighing 8-13 kg, were randomly divided into two groups (n=6). In the experimental group, the ACL reconstruction model of the right lower limb was prepared by using a single bundle of hamstring tendon, and the ACL of the right lower limb was only cut off in the control group. The survival of animals in the two groups was observed after operation. Before operation and at 3, 6, and 12 months after operation, the knee range of motion, thigh circumference, and calf circumference of the two groups were measured; the anterior tibial translation D-value (ATTD) was measured by Ligs joint ligament digital body examination instrument under the loads of 13-20 N, respectively. At the same time, the experimental group underwent MRI examination to observe the graft morphology and the signal/ noise quotient (SNQ) was caculated. Results All animals survived to the end of the experiment. In the experimental group, the knee range of motion, thigh circumference, and calf circumference decreased first and then gradually increased after operation; the above indexes were significantly lower at 3 and 6 months after operation than before operation (P<0.05), and no significant difference was found between pre-operation and 12 months after operation (P>0.05). In the control group, there was no significant change in knee range of motion after operation, showing no significant difference between pre- and post-operation (P>0.05), but the thigh circumference and calf circumference gradually significantly decreased with time (P<0.05), and the difference was significant when compared with those before operation (P<0.05). At 6 and 12 months after operation, the thigh circumference and calf circumference were significantly larger in the experimental group than in the control group (P<0.05). At 3 and 6 months after operation, the knee range of motion was significantly smaller in the experimental group than in the control group (P<0.05). Under the loading condition of 13-20 N, the ATTD in the experimental group increased first and then decreased after operation; and the ATTD significantly increased at 3, 6 months after operation when compared with the value before operation (P<0.05). But there was no significant difference between the pre-operation and 12 months after operation (P>0.05). There was no significant change in ATTD in the control group at 3, 6, and 12 months after operation (P>0.05), and which were significantly higher than those before operation (P<0.05). At each time point after operation, the ATTD was significantly smaller in the experimental group than in the control group under the same load (P<0.05). The MRI examination of the experimental group showed that the ACL boundary gradually became clear after reconstruction and was covered by the synovial membrane. The SNQ at each time point after operation was significantly higher than that before operation, but gradually decreased with time, and the differences between time points were significant (P<0.05). Conclusion The ACL reconstruction model in cynomolgus monkey with autogenous hamstring tendon transplantation was successfully established.

Citation： LU Xiaojun, YU Yang, XIE Bing, WANG Guoliang, YANG Tengyun, XIONG Bohan, LIU Jinrui, LI Yanlin. Establishment of anterior cruciate ligament reconstruction model in cynomolgus monkey with autogenous hamstring tendon transplantation. Chinese Journal of Reparative and Reconstructive Surgery, 2023, 37(7): 862-867. doi: 10.7507/1002-1892.202303103 Copy

1.	Hassebrock JD, Gulbrandsen MT, Asprey WL, et al. Knee ligament anatomy and biomechanics. Sports Med Arthrosc Rev, 2020, 28(3): 80-86.
2.	Rodríguez-Merchán EC. Anterior cruciate ligament reconstruction: is biological augmentation beneficial? Int J Mol Sci, 2021, 22(22): 12566. doi: 10.3390/ijms222212566.
3.	Cardona-Ramirez S, Cook JL, Stoker AM, et al. Small laboratory animal models of anterior cruciate ligament reconstruction. J Orthop Res, 2022, 40(9): 1967-1980.
4.	Proffen BL, McElfresh M, Fleming BC, et al. A comparative anatomical study of the human knee and six animal species. Knee, 2012, 19(4): 493-499.
5.	Madry H, Ochi M, Cucchiarini M, et al. Large animal models in experimental knee sports surgery: focus on clinical translation. J Exp Orthop, 2015, 2(1): 9. doi: 10.1186/s40634-015-0025-1.
6.	Liu G, Zhang L, Zhou X, et al. Selection and investigation of a primate model of spontaneous degenerative knee osteoarthritis, the cynomolgus monkey (macaca fascicularis). Med Sci Monit, 2018, 24: 4516-4527.
7.	Ogawa S, Awaga Y, Takashima M, et al. Knee osteoarthritis pain following medial meniscectomy in the nonhuman primate. Osteoarthritis Cartilage, 2016, 24(7): 1190-1199.
8.	Carlson CS, Loeser RF, Purser CB, et al. Osteoarthritis in cynomolgus macaques Ⅲ: Effects of age, gender, and subchondral bone thickness on the severity of disease. J Bone Miner Res, 1996, 11(9): 1209-1217.
9.	Zhang L, Wang R, Zhang P, et al. The employment of cynomolgus monkey as proprioceptive deficit model of the anterior cruciate ligament. J Orthop Surg (Hong Kong), 2021, 29(2): 23094990211015519. doi: 10.1177/23094990211015519.
10.	常晗, 唐翔宇, 曲峰, 等. 前交叉韧带重建肌腱移植物内预置高强度缝线预防蠕变的实验研究. 中国修复重建外科杂志, 2017, 31(1): 42-45.
11.	Czuppon S, Racette BA, Klein SE, et al. Variables associated with return to sport following anterior cruciate ligament reconstruction: a systematic review. Br J Sports Med, 2014, 48(5): 356-364.
12.	邹国耀, 宋恩鸿, 李张. 股骨隧道角度对兔前交叉韧带重建术后骨隧道影响的初步探讨. 中国修复重建外科杂志, 2015, 29(2): 171-174.
13.	Zhang L, Guan T, Qi J, et al. A model of anterior cruciate ligament injury in cynomolgus monkeys developed via arthroscopic surgery. Exp Ther Med, 2018, 15(3): 2239-2246.
14.	程聪, 任士友, 陈鹏, 等. 内侧半月板损伤对前交叉韧带重建后失效的诊断意义. 中国修复重建外科杂志, 2016, 30(5): 558-561.
15.	张辉, 杨远, 陈斐, 等. MRI检查在前交叉韧带损伤诊断中的应用. 国际骨科学杂志, 2020, 41(5): 280-284.
16.	马勇, 张家豪, 蒋艳芳, 等. 股骨骨道位置对前交叉韧带术后半年腘绳肌腱移植物信噪比的影响. 中国运动医学杂志, 2019, 38(6): 469-473.
17.	Franck F, Saithna A, Vieira TD, et al. Return to sport composite test after anterior cruciate ligament reconstruction (K-STARTS): Factors affecting return to sport test score in a retrospective analysis of 676 patients. Sports Health, 2021, 13(4): 364-372.
18.	刘佳, 高娟, 李嫚, 等. Ligs关节韧带数字体查仪与KT-1000测量前交叉韧带损伤后膝关节前向不稳定的对比研究. 中国运动医学杂志, 2023, 42(1): 14-18.
19.	王云鹭, 李锡勇, 刘伦, 等. 前交叉韧带重建术后移植物愈合的研究进展. 实用骨科杂志, 2023, 29(1): 47-51.

1. Hassebrock JD, Gulbrandsen MT, Asprey WL, et al. Knee ligament anatomy and biomechanics. Sports Med Arthrosc Rev, 2020, 28(3): 80-86.
2. Rodríguez-Merchán EC. Anterior cruciate ligament reconstruction: is biological augmentation beneficial? Int J Mol Sci, 2021, 22(22): 12566. doi: 10.3390/ijms222212566.
3. Cardona-Ramirez S, Cook JL, Stoker AM, et al. Small laboratory animal models of anterior cruciate ligament reconstruction. J Orthop Res, 2022, 40(9): 1967-1980.
4. Proffen BL, McElfresh M, Fleming BC, et al. A comparative anatomical study of the human knee and six animal species. Knee, 2012, 19(4): 493-499.
5. Madry H, Ochi M, Cucchiarini M, et al. Large animal models in experimental knee sports surgery: focus on clinical translation. J Exp Orthop, 2015, 2(1): 9. doi: 10.1186/s40634-015-0025-1.
6. Liu G, Zhang L, Zhou X, et al. Selection and investigation of a primate model of spontaneous degenerative knee osteoarthritis, the cynomolgus monkey (macaca fascicularis). Med Sci Monit, 2018, 24: 4516-4527.
7. Ogawa S, Awaga Y, Takashima M, et al. Knee osteoarthritis pain following medial meniscectomy in the nonhuman primate. Osteoarthritis Cartilage, 2016, 24(7): 1190-1199.
8. Carlson CS, Loeser RF, Purser CB, et al. Osteoarthritis in cynomolgus macaques Ⅲ: Effects of age, gender, and subchondral bone thickness on the severity of disease. J Bone Miner Res, 1996, 11(9): 1209-1217.
9. Zhang L, Wang R, Zhang P, et al. The employment of cynomolgus monkey as proprioceptive deficit model of the anterior cruciate ligament. J Orthop Surg (Hong Kong), 2021, 29(2): 23094990211015519. doi: 10.1177/23094990211015519.
10. 常晗, 唐翔宇, 曲峰, 等. 前交叉韧带重建肌腱移植物内预置高强度缝线预防蠕变的实验研究. 中国修复重建外科杂志, 2017, 31(1): 42-45.
11. Czuppon S, Racette BA, Klein SE, et al. Variables associated with return to sport following anterior cruciate ligament reconstruction: a systematic review. Br J Sports Med, 2014, 48(5): 356-364.
12. 邹国耀, 宋恩鸿, 李张. 股骨隧道角度对兔前交叉韧带重建术后骨隧道影响的初步探讨. 中国修复重建外科杂志, 2015, 29(2): 171-174.
13. Zhang L, Guan T, Qi J, et al. A model of anterior cruciate ligament injury in cynomolgus monkeys developed via arthroscopic surgery. Exp Ther Med, 2018, 15(3): 2239-2246.
14. 程聪, 任士友, 陈鹏, 等. 内侧半月板损伤对前交叉韧带重建后失效的诊断意义. 中国修复重建外科杂志, 2016, 30(5): 558-561.
15. 张辉, 杨远, 陈斐, 等. MRI检查在前交叉韧带损伤诊断中的应用. 国际骨科学杂志, 2020, 41(5): 280-284.
16. 马勇, 张家豪, 蒋艳芳, 等. 股骨骨道位置对前交叉韧带术后半年腘绳肌腱移植物信噪比的影响. 中国运动医学杂志, 2019, 38(6): 469-473.
17. Franck F, Saithna A, Vieira TD, et al. Return to sport composite test after anterior cruciate ligament reconstruction (K-STARTS): Factors affecting return to sport test score in a retrospective analysis of 676 patients. Sports Health, 2021, 13(4): 364-372.
18. 刘佳, 高娟, 李嫚, 等. Ligs关节韧带数字体查仪与KT-1000测量前交叉韧带损伤后膝关节前向不稳定的对比研究. 中国运动医学杂志, 2023, 42(1): 14-18.
19. 王云鹭, 李锡勇, 刘伦, 等. 前交叉韧带重建术后移植物愈合的研究进展. 实用骨科杂志, 2023, 29(1): 47-51.

Chinese Journal of Reparative and Reconstructive Surgery

Establishment of anterior cruciate ligament reconstruction model in cynomolgus monkey with autogenous hamstring tendon transplantation

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