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. 前交叉韌帶重建肌腱移植物內預置高強度縫線預防蠕變的實驗研究. 中國修復重建外科雜志, 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.	鄒國耀, 宋恩鴻, 李張. 股骨隧道角度對兔前交叉韌帶重建術后骨隧道影響的初步探討. 中國修復重建外科雜志, 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.	程聰, 任士友, 陳鵬, 等. 內側半月板損傷對前交叉韌帶重建后失效的診斷意義. 中國修復重建外科雜志, 2016, 30(5): 558-561.
15.	張輝, 楊遠, 陳斐, 等. MRI檢查在前交叉韌帶損傷診斷中的應用. 國際骨科學雜志, 2020, 41(5): 280-284.
16.	馬勇, 張家豪, 蔣艷芳, 等. 股骨骨道位置對前交叉韌帶術后半年腘繩肌腱移植物信噪比的影響. 中國運動醫學雜志, 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.	劉佳, 高娟, 李嫚, 等. Ligs關節韌帶數字體查儀與KT-1000測量前交叉韌帶損傷后膝關節前向不穩定的對比研究. 中國運動醫學雜志, 2023, 42(1): 14-18.
19.	王云鷺, 李錫勇, 劉倫, 等. 前交叉韌帶重建術后移植物愈合的研究進展. 實用骨科雜志, 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. 前交叉韌帶重建肌腱移植物內預置高強度縫線預防蠕變的實驗研究. 中國修復重建外科雜志, 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. 鄒國耀, 宋恩鴻, 李張. 股骨隧道角度對兔前交叉韌帶重建術后骨隧道影響的初步探討. 中國修復重建外科雜志, 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. 程聰, 任士友, 陳鵬, 等. 內側半月板損傷對前交叉韌帶重建后失效的診斷意義. 中國修復重建外科雜志, 2016, 30(5): 558-561.
15. 張輝, 楊遠, 陳斐, 等. MRI檢查在前交叉韌帶損傷診斷中的應用. 國際骨科學雜志, 2020, 41(5): 280-284.
16. 馬勇, 張家豪, 蔣艷芳, 等. 股骨骨道位置對前交叉韌帶術后半年腘繩肌腱移植物信噪比的影響. 中國運動醫學雜志, 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. 劉佳, 高娟, 李嫚, 等. Ligs關節韌帶數字體查儀與KT-1000測量前交叉韌帶損傷后膝關節前向不穩定的對比研究. 中國運動醫學雜志, 2023, 42(1): 14-18.
19. 王云鷺, 李錫勇, 劉倫, 等. 前交叉韌帶重建術后移植物愈合的研究進展. 實用骨科雜志, 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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