ABSTRACT
Tendinopathies and osteoarthritis developed after cartilage damage are chronic health problems that decrease the patient’s quality of life. Osteoporosis is another important health problem leading to fractures. In the treatment of osteoporotic fractures, satisfactory results cannot be achieved. In recent years, studies intended to understand the mechanisms underlying the fracture healing, and also, to provide the regeneration of cartilage and tendon have increased. Animal models are used to improve understanding of complex processes and related mechanisms in fracture healing. In cartilage and tendon pathologies, it is inevitable to use animal models in order to investigate new surgical methods and to develop and test surgical implants and materials. While tissue engineering models aim to produce new cells that will provide regeneration, orthopedic surgery models focus on implant and biomechanical research. In planning pre-clinical orthopedic studies, appropriate methods should be chosen in order to evaluate the results correctly. Histological methods are important in evaluating the microstructural properties of tissues. In addition, quantitative assessments obtained by imaging modalities provide valuable information for adaptation of the results to the clinic.
References
1Harvey EJ, Giannoudis PV, Martineau PA, et al. Preclinical animal models in trauma research. J Orthop Trauma 2011;25:488-493.
2Hast MW, Zuskov A, Soslowsky LJ. The role of animal models in tendon research. Bone Joint Res 2014;3:193-202.
3Bonnarens F, Einhorn TA. Production of a standard closed fracture in laboratory animal bone. J Orthop Res 1984;2:97-101.
4Tägil M, McDonald MM, Morse A, et al. Intermittent PTH(1-34) does not increase union rates in open rat femoral fractures and exhibits attenuated anabolic effects compared to closed fractures. Bone 2010;46:852-859.
5Kokubu T, Hak DJ, Hazelwood SJ, Reddi AH. Development of an atrophic nonunion model and comparison to a closed healing fracture in rat femur. J Orthop Res 2003;21:503-510.
6Marturanoa JE, Clevelanda BC, Byrne MA, O’Connell SL, Wixted JJ, Billiar KL. An improved murine femur fracture device for bone healing studies. J Biomech 2008;41:1222-1228.
7Schindeler A, Morse A, Harry L, et al. Models of tibial fracture healing in normal and Nf1-deficient mice. J Orthop Res 2008;26:1053-1060.
8Röntgen V, Blakytny R, Matthys R, et al. Fracture healing in mice under controlled rigid and flexible conditions using an adjustable external fixator. J Orthop Res 2010;28:1456-1462.
9Harvey EJ, Giannoudis PV, Martineau PA, et al. Preclinical animal models in trauma research. J Orthop Trauma 2011;25:488-493.
10Roohani-Esfahani SI, Dunstan CR, Davies B, Pearce S, Williams R, Zreiqat H. Repairing a critical-sized bone defect with highly porous modified and unmodified baghdadite scaffolds. Acta Biomater 2012;8:4162-4172.
11Gosain AK, Song L, Yu P, et al. Osteogenesis in cranial defects: Reassessment of the concept of critical size and the expression of TGF-beta isoforms. Plast Reconstr Surg 2000;106:360-371.
12Martini L, Fini M, Giavaresi G, Giardino R. Sheep model in orthopedic research: a literature review. Comp Med 2001;51:292-299.
13Pearce AI, Richards RG, Milz S, Schneider E, Pearce SG. Animal models for implant biomaterial research in bone: a review. Eur Cell Mater 2007;13:1-10.
14Schindeler A, Mills RC, Bobyn JD, Little DG. Preclinical models for orthopedic research and bone tissue engineering. J Orthop Res 2018;36:832-840.
15Tawonsawatruk T, Hamilton DF, Simpson AH. Validation of the use of radiographic fracture-healing scores in a small animal model. J Orthop Res 2014;32:1117-1119.
16Morgan EF, Mason ZD, Chien KB, et al. Microcomputed tomography assessment of fracture healing: relationships among callus structure, composition, and mechanical function. Bone 2009;44:335-344.
17Bouxsein ML, Boyd SK, Christiansen BA, Guldberg RE, Jepsen KJ, Müller R. Guidelines for assessment of bone microstructure in rodents using micro-computed tomography. J Bone Miner Res. 2010;25:1468-1486.
18Strømsøe K. Fracture fixation problems in osteoporosis. Injury 2004;35:107-113.
19Egermann M, Goldhahn J, Schneider E. Animal models for fracture treatment in osteoporosis. Osteoporos Int. 2005;16:S129-138.
20Thompson DD, Simmons HA, Pirie CM, Ke HZ. FDA Guidelines and animal models for osteoporosis. Bone 1995;17:125S-133S.
21Wronski TJ, Dann LM, Scott KS, Cintrón M. Long-term effects of ovariectomy and aging on the rat skeleton. Calcif Tissue Int 1989;45:360-366.
22Miller SC, Wronski TJ. Long-term osteopenic changes in cancellous bone structure in ovariectomized rats. Anat Rec 1993;236:433-441.
23Brockstedt H, Kassem M, Eriksen EF, Mosekilde L, Melsen F. Age and sex-related changes in iliac cortical bone mass and remodeling. Bone 1993;14:681-691.
24Namkung-Matthai H, Appleyard R, Jansen J, et al. Osteoporosis influences the early period of fracture healing in a rat osteoporotic model. Bone 2001;28:80-86.
25Lill CA, Hesseln J, Schlegel U, Eckhardt C, Goldhahn J, Schneider E. Biomechanical evaluation of healing in a non-critical defect in a large animal model of osteoporosis. J Orthop Res 2003;21:836-842.
26Ahern BJ, Parvizi J, Boston R, Schaer TP. Preclinical animal models in single site cartilage defect testing: a systematic review. Osteoarthritis Cartilage 2009;17:705-713.
27Hunziker EB, Quinn TM, Häuselmann HJ. Quantitative structural organization of normal adult human articular cartilage. Osteoarthritis Cartilage 2002;10:564-572.
28Hoemann C, Kandel R, Roberts S, et al. International cartilage repair society (ICRS) recommended guidelines for histological endpoints for cartilage repair studies in animal models and clinical trials. Cartilage 2011;2:153-172.
29Nordling C, Karlsson-Parra A, Jansson L, Holmdahl R, Klareskog L. Characterization of spontaneously occurring arthritis in male DBA/1 mice. Arthritis Rheum 1992;35:717-722.
30Chu CR, Szczodry M, Bruno S. Animal models for cartilage regeneration and repair. Tissue Eng Part B Rev 2010;16:105-115.
31Ramallal M, Maneiro E, López E, et al. Xeno-implantation of pig chondrocytes into rabbit to treat localized articular cartilage defects: an animal model. Wound Repair Regen 2004;12:337-345.
32Hoemann CD, Sun J, Légaré A, McKee MD, Buschmann MD. Tissue engineering of cartilage using an injectable and adhesive chitosan-based cell-delivery vehicle. Osteoarthritis Cartilage 2005;13:318-329.
33Hurtig MB, Buschmann MD, Fortier LA, et al. Preclinical studies for cartilage repair: recommendations from the international cartilage repair society. Cartilage 2011;2:137-152.
34Lu Y, Hayashi K, Hecht P, Fanton GS, Thabit G. The effect of monopolar radiofrequency energy on partial-thickness defects of articular cartilage. Arthroscopy 2000;16:527-536.
35Kandel RA, Grynpas M, Pilliar R, Lee J. Repair of osteochondral defects with biphasic cartilage-calcium polyphosphate constructs in a Sheep model. Biomaterials 2006;27:4120-4231.
36Orth P, Goebel L, Wolfram U, et al. Effect of subchondral drilling on the microarchitecture of subchondral bone: analysis in a large animal model at 6 months. Am J Sports Med 2012;40:828-836.
37Brehm W, Aklin B, Yamashita T, et al. Repair of superficial osteochondral defects with an autologous scaffold-free cartilage construct in a caprine model: implantation method and short-term results. Osteoarthritis Cartilage 2006;14:1214-1226.
38Brittberg M, Sjögren-Jansson E, Lindahl A, Peterson L. Influence of fibrin sealant (Tisseel) on osteochondral defect repair in the rabbit knee. Biomaterials 1997;18:235-242.
39Chiang H, Kuo TF, Tsai CC, et al. Repair of porcine articular cartilage defect with autologous chondrocyte transplantation. J Orthop Res 2005;23:584-593.
40Hembry RM, Dyce J, Driesang I, et al. Immunolocalization of matrix metalloproteinases in partial-thickness defects in pig articular cartilage. A preliminary report. J Bone Joint Surg Am 2001;83-A:826-838.
41Vasara AI, Hyttinen MM, Pulliainen O, et al. Immature porcine knee cartilage lesions show good healing with or without autologous chondrocyte transplantation. Osteoarthritis Cartilage 2006;14:1066-1074.
42Hurtig MB, Fretz PB, Doige CE, Schnurr DL. Effects of lesion size and location on equine articular cartilage repair. Can J Vet Res 1988;52:137-146.
43Frisbie DD, Trotter GW, Powers BE, et al. Arthroscopic subchondral bone plate microfracture technique augments healing of large chondral defects in the radial carpal bone and medial femoral condyle of horses. Vet Surg 1999;28:242-255.
44Barnewitz D, Endres M, Krüger I, et al. Treatment of articular cartilage defects in horses with polymer-based cartilage tissue engineering grafts. Biomaterials 2006;27:2882-2889.
45Hast MW, Zuskov A, Soslowsky LJ. The role of animal models in tendon research. Bone Joint Res 2014;3:193-202.
46Soslowsky LJ, Carpenter JE, DeBano CM, Banerji I, Moalli MR. Development and use of an animal model for investigations on rotator cuff disease. J Shoulder Elbow Surg 1996;5:383-392.
47Liu X, Laron D, Natsuhara K, Manzano G, Kim HT, Feeley BT. A mouse model of massive rotator cuff tears. J Bone Joint Surg Am 2012;94:e41.
48Kim HM, Galatz LM, Lim C, Havlioglu N, Thomopoulos S. The effect of tear size and nerve injury on rotator cuff muscle fatty degeneration in a rodent animal model. J Shoulder Elbow Surg 2012;21:847-858.
49Quigley RJ, Gupta A, Oh JH, et al. Biomechanical comparison of single-row, double-row, and transosseous-equivalent repair techniques after healing in an animal rotator cuff tear model. J Orthop Res 2013;31:1254-1260.
50Maguire M, Goldberg J, Bokor D, et al. Biomechanical evaluation of four different transosseous-equivalent/suture bridge rotator cuff repairs. Knee Surg Sports Traumatol Arthrosc 2011;19:1582-1587.
51Onay U, Akpınar S, Akgün RC, Balçık C, Tuncay IC. Comparison of repair techniques in small and medium-sized rotator cuff tears in cadaveric sheep shoulders. Acta Orthop Traumatol Turc 2013;47:179-183.
52Hapa O, Cakıcı H, Kükner A, Aygün H, Sarkalkan N, Baysal G. Effect of platelet-rich plasma on tendon-to-bone healing after rotator cuff repair in rats: an in vivo experimental study. Acta Orthop Traumatol Turc 2012;46:301-307.
53Kida Y, Morihara T, Matsuda K, et al. Bone marrow-derived cells from the footprint infiltrate into the repaired rotator cuff. J Shoulder Elbow Surg 2013;22:197-205.
54Kim YS, Lee HJ, Ok JH, Park JS, Kim DW. Survivorship of implanted bone marrow-derived mesenchymal stem cells in acute rotator cuff tear. J Shoulder Elbow Surg 2013;22:1037-1045.
55Levy DM, Saifi C, Perri JL, Zhang R, Gardner TR, Ahmad CS. Rotator cuff repair augmentation with local autogenous bone marrow via humeral cannulation in a rat model. J Shoulder Elbow Surg 2013;22:1256-64.
56Gladstone JN, Bishop JY, Lo IK, Flatow EL. Fatty infiltration and atrophy of the rotator cuff do not improve after rotator cuff repair and correlate with poor functional outcome. Am J Sports Med 2007;35:719-728.
57Doro LC, Ladd B, Hughes RE, Chenevert TL. Validation of an adapted MRI pulse sequence for quantification of fatty infiltration in muscle. Magn Reson Imaging 2009;27:823-827.
58Coleman SH, Fealy S, Ehteshami JR, et al. Chronic rotator cuff injury and repair model in sheep. J Bone Joint Surg Am 2003;85-A:2391-2402.
59Frey E, Regenfelder F, Sussmann P, et al. Adipogenic and myogenic gene expression in rotator cuff muscle of the sheep after tendon tear. J Orthop Res 2009;27:504-509.
60Gerber C, Meyer DC, Frey E, et al. Neer Award 2007: Reversion of structural muscle changes caused by chronic rotator cuff tears using continuous musculotendinous traction. An experimental study in sheep. J Shoulder Elbow Surg 2009;18:163-171.
61Goutallier D, Postel JM, Bernageau J, Lavau L, Voisin MC. Fatty muscle degeneration in cuff ruptures. Pre- and postoperative evaluation by CT scan. Clin Orthop Relat Res 1994;304:78-83.
62Samagh SP, Kramer EJ, Melkus G, et al. MRI quantification of fatty infiltration and muscle atrophy in a mouse model of rotator cuff tears. J Orthop Res 2013;31:421-426.
63Bell R, Li J, Gorski DJ, et al. Controlled treadmill exercise eliminates chondroid deposits and restores tensile properties in a new murine tendinopathy model. J Biomech 2013;46:498-505.
64Andersson G, Backman LJ, Scott A, Lorentzon R, Forsgren S, Danielson P. Substance P accelerates hypercellularity and angiogenesis in tendon tissue and enhances paratendinitis in response to Achilles tendon overuse in a tendinopathy model. Br J Sports Med 2011;45:1017-1022.
65Gehmert S, Jung EM, Kügler T, et al. Sonoelastography can be used to monitor the restoration of Achilles tendon elasticity after injury. Ultraschall Med 2012;33:581-586.
66Chang KV, Wu CH, Ding YH, et al. Application of contrast-enhanced sonography with time-intensity curve analysis to explore hypervascularity in Achilles tendinopathy by using a rabbit model. J Ultrasound Med 2012;31:737-746.
