J Korean Orthop Assoc.  2017 Aug;52(4):344-349. 10.4055/jkoa.2017.52.4.344.

Animal Models of Orthopedic Research: A Spinal Fusion Model

• Lee JH
• Nam Y
• Lee JH

• KMID: 2387793
• DOI: http://doi.org/10.4055/jkoa.2017.52.4.344

Abstract

The incidence of spinal fusion surgery has increased due to an increase in the incidence of degenerative spinal disease or trauma. Moreover, the development of various kinds of implants and bone graft substitutes has also increased. The animal models of spinal fusion are useful methods in evaluating the effectiveness of the newly developed spinal implants or bone graft substitutes. The most widely used animal models of spinal fusion are posterolateral fusion model, posterior fusion model, and anterior interbody fusion model. Mice, rats, rabbits, dogs, pigs, goats, sheep, and primates are frequently used in animal models of spinal fusion. Small animals are implanted with a bone graft substitute without internal fixation; however middle- or large-sized animals are implanted with a bone graft substitute using pedicle screws or cages. Small animals are easy to handle due to their size, but have different anatomical or biomechanical reactions with the human body. Middle- or large-sized animals have characteristics like the human body, but they are difficult to handle or there is an ethical problem. The fusion status is evaluated by manual palpation, mechanical testing using Instron, and radiologic techniques such as computed tomography, micro-computed tomography or undecalcified histology. The fusion rate and duration required for successful fusion differ according to the species and anatomical site. We have identified and reviewed several typical animal models of spinal fusion.

Keyword

spinal fusion; animal model; review; posterior fusion; anterior fusion

MeSH Terms

Animals*
Dogs
Goats
Human Body
Incidence
Mice
Models, Animal*
Orthopedics*
Palpation
Pedicle Screws
Primates
Rabbits
Rats
Sheep
Spinal Diseases
Spinal Fusion*
Swine
Transplants

Reference

1. Albee FH. An experimental study of bone growth and the spinal bone transplant. JAMA. 1913; 60:1044–9.

2. Khan SN, Lane JM. Spinal fusion surgery: animal models for tissue-engineered bone constructs. Biomaterials. 2004; 25:1475–85.

3. Drespe IH, Polzhofer GK, Turner AS, Grauer JN. Animal models for spinal fusion. Spine J. 2005; 5:209S–16S.

4. Lee JH, Lee CK, Chang BS. . In vivo study of novel biodegradable and osteoconductive CaO-SiO2-B2O3 glass-ceramics. J Biomed Mater Res A. 2006; 77:362–9.

5. Lee JH, Yu CH, Yang JJ. . Comparative study of fusion rate induced by different dosages of Escherichia coli-derived recombinant human bone morphogenetic protein-2 using hydroxyapatite carrier. Spine J. 2012; 12:239–48.

6. Hwang CJ, Lee JH, Baek HR, Chang BS, Lee CK. Evaluation of the efficacy of Escherichia coli-derived recombinant human bone morphogenetic protein-2 in a mini-pig spinal anterior interbody fusion model. Bone Joint J. 2013; 95:217–23.

7. Rao RD, Bagaria VB, Cooley BC. Posterolateral intertransverse lumbar fusion in a mouse model: surgical anatomy and operative technique. Spine J. 2007; 7:61–7.

8. Alli PM, Pinn ML, Jaffee EM, McFadden JM, Kuhajda FP. Fatty acid synthase inhibitors are chemopreventive for mammary cancer in neu-N transgenic mice. Oncogene. 2005; 24:39–46.

9. Alexanian AR, Kurpad SN. Quiescent neural cells regain multipotent stem cell characteristics influenced by adult neural stem cells in co-culture. Exp Neurol. 2005; 191:193–7.

10. Sandhu HS, Khan SN. Animal models for preclinical assessment of bone morphogenetic proteins in the spine. Spine (Phila Pa 1976). 2002; 27:S32–8.

11. Wang JC, Kanim LE, Yoo S, Campbell PA, Berk AJ, Lieberman JR. Effect of regional gene therapy with bone morphogenetic protein-2-producing bone marrow cells on spinal fusion in rats. J Bone Joint Surg Am. 2003; 85:905–11.

12. Grauer JN, Bomback DA, Lugo R, Troiano NW, Patel TC, Friedlaender GE. Posterolateral lumbar fusions in athymic rats: characterization of a model. Spine J. 2004; 4:281–6.

13. Salamon ML, Althausen PL, Gupta MC, Laubach J. The effects of BMP-7 in a rat posterolateral intertransverse process fusion model. J Spinal Disord Tech. 2003; 16:90–5.

14. Cui Q, Ming Xiao Z, Balian G, Wang GJ. Comparison of lumbar spine fusion using mixed and cloned marrow cells. Spine (Phila Pa 1976). 2001; 26:2305–10.

15. Kim HS, Viggeswarapu M, Boden SD. . Overcoming the immune response to permit ex vivo gene therapy for spine fusion with human type 5 adenoviral delivery of the LIM mineralization protein-1 cDNA. Spine (Phila Pa 1976). 2003; 28:219–26.

16. Boden SD, Schimandle JH, Hutton WC. An experimental lumbar intertransverse process spinal fusion model. Radiographic, histologic, and biomechanical healing characteristics. Spine (Phila Pa 1976). 1995; 20:412–20.

17. Morone MA, Boden SD. Experimental posterolateral lumbar spinal fusion with a demineralized bone matrix gel. Spine (Phila Pa 1976). 1998; 23:159–67.

18. Lindholm TS, Ragni P, Lindholm TC. Response of bone marrow stroma cells to demineralized cortical bone matrix in experimental spinal fusion in rabbits. Clin Orthop Relat Res. 1988; 230:296–302.

19. Schimandle JH, Boden SD, Hutton WC. Experimental spinal fusion with recombinant human bone morphogenetic protein-2. Spine (Phila Pa 1976). 1995; 20:1326–37.

20. Riew KD, Long J, Rhee J. . Time-dependent inhibitory effects of indomethacin on spinal fusion. J Bone Joint Surg Am. 2003; 85:632–4.

21. Grauer JN, Patel TC, Erulkar JS, Troiano NW, Panjabi MM, Friedlaender GE. 2000 young investigator research award winner. Evaluation of OP-1 as a graft substitute for intertransverse process lumbar fusion. Spine (Phila Pa 1976). 2001; 26:127–33.

22. Karaismailoğlu TN, Tomak Y, Andaç A, Ergün E. Comparison of autograft, coralline graft, and xenograft in promoting posterior spinal fusion. Acta Orthop Traumatol Turc. 2002; 36:147–54.

23. Fuller DA, Stevenson S, Emery SE. The effects of internal fixation on calcium carbonate. Ceramic anterior spinal fusion in dogs. Spine (Phila Pa 1976). 1996; 21:2131–6.

24. Cook SD, Dalton JE, Prewett AB, Whitecloud TS 3rd. In vivo evaluation of demineralized bone matrix as a bone graft substitute for posterior spinal fusion. Spine (Phila Pa 1976). 1995; 20:877–86.

25. Kioschos HC, Asher MA, Lark RG, Harner EJ. Overpowering the crankshaft mechanism. The effect of posterior spinal fusion with and without stiff transpedicular fixation on anterior spinal column growth in immature canines. Spine (Phila Pa 1976). 1996; 21:1168–73.

26. Muschler GF, Negami S, Hyodo A, Gaisser D, Easley K, Kambic H. Evaluation of collagen ceramic composite graft materials in a spinal fusion model. Clin Orthop Relat Res. 1996; 328:250–60.

27. Cahill DW, Martin GJ Jr, Hajjar MV, Sonstein W, Graham LB, Engelman RW. Suitability of bioresorbable cages for anterior cervical fusion. J Neurosurg. 2003; 98:S195–201.

28. Toth JM, An HS, Lim TH. . Evaluation of porous biphasic calcium phosphate ceramics for anterior cervical interbody fusion in a caprine model. Spine (Phila Pa 1976). 1995; 20:2203–10.

29. Zdeblick TA, Cooke ME, Wilson D, Kunz DN, McCabe R. Anterior cervical discectomy, fusion, and plating. A comparative animal study. Spine (Phila Pa 1976). 1993; 18:1974–83.

30. Kandziora F, Pflugmacher R, Schäfer J, et al. Biomechanical comparison of cervical spine interbody fusion cages. Spine (Phila Pa 1976). 2001; 26:1850–7.

31. Spivak JM, Chen D, Kummer FJ. The effect of locking fixation screws on the stability of anterior cervical plating. Spine (Phila Pa 1976). 1999; 24:334–8.

32. Sandhu HS, Toth JM, Diwan AD. . Histologic evaluation of the efficacy of rhBMP-2 compared with autograft bone in sheep spinal anterior interbody fusion. Spine (Phila Pa 1976). 2002; 27:567–75.

33. Kong CB, Lee JH, Baek HR, Lee CK, Chang BS. Posterolateral lumbar fusion using Escherichia coli-derived rhBMP-2/ hydroxyapatite in the mini pig. Spine J. 2014; 14:2959–67.

34. Hecht BP, Fischgrund JS, Herkowitz HN, Penman L, Toth JM, Shirkhoda A. The use of recombinant human bone morphogenetic protein 2 (rhBMP-2) to promote spinal fusion in a nonhuman primate anterior interbody fusion model. Spine (Phila Pa 1976). 1999; 24:629–36.

35. Akamaru T, Suh D, Boden SD, Kim HS, Minamide A. Louis-Ugbo J. Simple carrier matrix modifications can enhance delivery of recombinant human bone morphogenetic protein-2 for posterolateral spine fusion. Spine (Phila Pa 1976). 2003; 28:429–34.

36. Suh DY, Boden SD, Louis-Ugbo J. . Delivery of recombinant human bone morphogenetic protein-2 using a compression-resistant matrix in posterolateral spine fusion in the rabbit and in the non-human primate. Spine (Phila Pa 1976). 2002; 27:353–60.