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Animal model for chronic massive rotator cuff tear: behavioural and histologic analysis

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Knee Surgery, Sports Traumatology, Arthroscopy Aims and scope

Abstract

Purpose

Massive rotator cuff tears (MRCT) are usually chronic lesions that present associated degenerative changes of the myotendinous unit that have been implicated in limitations for surgical repair. In order to develop effective therapies, it is important to establish animal models that mimic the hallmarks of the injury itself. Therefore, in the present work, we aimed to (1) optimize a rodent animal model of MRCT that closely reproduces the fatty infiltration of the cuff muscles seen in humans and (2) describe the effects of unilateral or bilateral lesion in terms of histology and behaviour.

Methods

Massive tear was defined as two rotator cuff tendons—supraspinatus and infraspinatus—section. Twenty-one Wistar rats were randomly assigned to four groups: bilateral lesion (five animals), right-sided unilateral lesion (five animals), left-sided unilateral lesion (five animals) and control (six animals). Behaviour was analyzed with open field and staircase test, 16 weeks after lesion. After that, animals were killed, and the supraspinatus and infraspinatus muscles were processed.

Results

Histologic analysis revealed adipocytes, fatty infiltration and atrophy in the injured side with a greater consistency of these degenerative changes in the bilateral lesion group. Behaviour analysis revealed a significant functional impairment of the fine motor control of the forepaw analyzed in staircase test where the number of eaten pellets was significantly higher in sham animals (sham = 7 ± 5.0; left unilateral = 2.6 ± 3.0; right unilateral = 0 ± 0; and bilateral = 0 ± 0, p < 0.05). A trend to reach a lower level of steps, in more injured animals, was also observed (sham animals = 3 ± 1.6 > left unilateral = 2 ± 2.1 > right unilateral = 0.8 ± 1.3 > bilateral = 0.8 ± 1.1).

Conclusions

The present study has been able to establish an animal model that disclosed the hallmarks of MRCT. This can now be used as a valuable, cost-effective, pre-clinical instrument to assist in the development of advanced tissue engineered strategies. Moreover, this animal model overcomes some of the limitations of those that have been reported so far and thus represents a more reliable source for the assessment of future therapeutic strategies with potential clinical relevance.

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References

  1. Albritton MJ, Graham RD, Richards RS 2nd, Basamania CJ (2003) An anatomic study of the effects on the suprascapular nerve due to retraction of the supraspinatus muscle after a rotator cuff tear. J Shoulder Elbow Surg 12(5):497–500

    Article  PubMed  Google Scholar 

  2. Asami A, Sonohata M, Morisawa K (2000) Bilateral suprascapular nerve entrapment syndrome associated with rotator cuff tear. J Shoulder Elbow Surg 9(1):70–72

    Article  CAS  PubMed  Google Scholar 

  3. Barton ER, Gimbel JA, Williams GR, Soslowsky LJ (2005) Rat supraspinatus muscle atrophy after tendon detachment. J Orthop Res 23(2):259–265

    Article  PubMed  Google Scholar 

  4. Benson RT, McDonnell SM, Knowles HJ, Rees JL, Carr AJ, Hulley PA (2010) Tendinopathy and tears of the rotator cuff are associated with hypoxia and apoptosis. J Bone Joint Surg Br 92(3):448–453

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Boykin RE, Friedman DJ, Higgins LD, Warner JJ (2010) Suprascapular neuropathy. J Bone Joint Surg Am 92(13):2348–2364

    Article  PubMed  Google Scholar 

  6. Burkhart SS (1991) Arthroscopic treatment of massive rotator cuff tears. Clinical results and biomechanical rationale. Clin Orthop Relat Res 267:45–56

    PubMed  Google Scholar 

  7. Carpenter JE, Hankenson KD (2004) Animal models of tendon and ligament injuries for tissue engineering applications. Biomaterials 25(9):1715–1722

    Article  CAS  PubMed  Google Scholar 

  8. Chang CH, Chen CH, Su CY, Liu HT, Yu CM (2009) Rotator cuff repair with periosteum for enhancing tendon-bone healing: a biomechanical and histological study in rabbits. Knee Surg Sports Traumatol Arthrosc 17(12):1447–1453

    Article  PubMed  Google Scholar 

  9. Cofield RH, Parvizi J, Hoffmeyer PJ, Lanzer WL, Ilstrup DM, Rowland CM (2001) Surgical repair of chronic rotator cuff tears. A prospective long-term study. J Bone Joint Surg Am 83-A(1):71–77

    CAS  PubMed  Google Scholar 

  10. Coleman SH, Fealy S, Ehteshami JR, MacGillivray JD, Altchek DW, Warren RF, Turner AS (2003) Chronic rotator cuff injury and repair model in sheep. J Bone Joint Surg Am 85-A(12):2391–2402

    PubMed  Google Scholar 

  11. Constant CR, Murley AH (1987) A clinical method of functional assessment of the shoulder. Clin Orthop Relat Res 214:160–164

    PubMed  Google Scholar 

  12. Costouros JG, Porramatikul M, Lie DT, Warner JJ (2007) Reversal of suprascapular neuropathy following arthroscopic repair of massive supraspinatus and infraspinatus rotator cuff tears. Arthroscopy 23(11):1152–1161

    Article  PubMed  Google Scholar 

  13. DeOrio JK, Cofield RH (1984) Results of a second attempt at surgical repair of a failed initial rotator-cuff repair. J Bone Joint Surg Am 66(4):563–567

    CAS  PubMed  Google Scholar 

  14. Dourte LM, Perry SM, Getz CL, Soslowsky LJ (2010) Tendon properties remain altered in a chronic rat rotator cuff model. Clin Orthop Relat Res 468(6):1485–1492

    Article  PubMed Central  PubMed  Google Scholar 

  15. Ellera Gomes JL, da Silva RC, Silla LM, Abreu MR, Pellanda R (2012) Conventional rotator cuff repair complemented by the aid of mononuclear autologous stem cells. Knee Surg Sports Traumatol Arthrosc 20(2):373–377

    Article  PubMed Central  PubMed  Google Scholar 

  16. Fuchs B, Weishaupt D, Zanetti M, Hodler J, Gerber C (1999) Fatty degeneration of the muscles of the rotator cuff: assessment by computed tomography versus magnetic resonance imaging. J Shoulder Elbow Surg 8(6):599–605

    Article  CAS  PubMed  Google Scholar 

  17. Gerber C, Fuchs B, Hodler J (2000) The results of repair of massive tears of the rotator cuff. J Bone Joint Surg Am 82(4):505–515

    CAS  PubMed  Google Scholar 

  18. Gerber CMD, Nuss KM, Farshad M (2011) Anabolic steroids reduce muscle damage caused by rotator cuff tendon release in an experimental study in rabbits. J Bone Joint Surg Am 93(23):2189–2195

    Article  CAS  PubMed  Google Scholar 

  19. Gerber C, Meyer DC, Schneeberger AG, Hoppeler H, von Rechenberg B (2004) Effect of tendon release and delayed repair on the structure of the muscles of the rotator cuff: an experimental study in sheep. J Bone Joint Surg Am 86(9):1973–1982

    PubMed  Google Scholar 

  20. Gerber C, Wirth SH, Farshad M (2011) Treatment options for massive rotator cuff tears. J Shoulder Elbow Surg 20(2 Suppl):S20–S29

    Article  PubMed  Google Scholar 

  21. Gimbel JA, Van Kleunen JP, Mehta S, Perry SM, Williams GR, Soslowsky LJ (2004) Supraspinatus tendon organizational and mechanical properties in a chronic rotator cuff tear animal model. J Biomech 37(5):739–749

    Article  PubMed  Google Scholar 

  22. Gladstone JN, Bishop JY, Lo IK, Flatow EL (2007) 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 35(5):719–728

    Article  PubMed  Google Scholar 

  23. Goutallier D, Postel JM, Bernageau J, Lavau L, Voisin MC (1994) Fatty muscle degeneration in cuff ruptures. Pre- and postoperative evaluation by CT scan. Clin Orthop Relat Res 304:78–83

    PubMed  Google Scholar 

  24. Goutallier D, Postel JM, Gleyze P, Leguilloux P, Van Driessche S (2003) Influence of cuff muscle fatty degeneration on anatomic and functional outcomes after simple suture of full-thickness tears. J Shoulder Elbow Surg 12(6):550–554

    Article  PubMed  Google Scholar 

  25. Goutallier D, Postel JM, Lavau L, Bernageau J (1998) Influence of muscular degeneration of the supra- and infra-spinatus on the prognosis of surgical repair of the rotator cuff. Acta Orthop Belg 64(Suppl 2):42–45

    PubMed  Google Scholar 

  26. Goutallier D, Postel JM, Lavau L, Bernageau J (1999) Impact of fatty degeneration of the supraspinatus and infraspinatus muscles on the prognosis of surgical repair of the rotator cuff. Rev Chir Orthop Reparatrice Appar Mot 85(7):668–676

    CAS  PubMed  Google Scholar 

  27. Gulotta LV, Kovacevic D, Packer JD, Deng XH, Rodeo SA (2011) Bone marrow-derived mesenchymal stem cells transduced with scleraxis improve rotator cuff healing in a rat model. Am J Sports Med 39(6):1282–1289

    Article  PubMed  Google Scholar 

  28. Kim HM, Galatz LM, Lim C, Havlioglu N, Thomopoulos S (2012) The effect of tear size and nerve injury on rotator cuff muscle fatty degeneration in a rodent animal model. J Shoulder Elbow Surg 21(7):847–858

    Article  PubMed Central  PubMed  Google Scholar 

  29. Lee HJ, Kim YS, Ok JH, Song HJ (2013) Apoptosis occurs throughout the diseased rotator cuff. Am J Sports Med 41(10):2249–2255

    Article  PubMed  Google Scholar 

  30. Liem D, Lichtenberg S, Magosch P, Habermeyer P (2007) Magnetic resonance imaging of arthroscopic supraspinatus tendon repair. J Bone Joint Surg Am 89(8):1770–1776

    Article  PubMed  Google Scholar 

  31. Liu X, Laron D, Natsuhara K, Manzano G, Kim HT, Feeley BT (2012) A mouse model of massive rotator cuff tears. J Bone Joint Surg Am 94(7):e41

    Article  PubMed  Google Scholar 

  32. Liu X, Manzano G, Kim HT, Feeley BT (2011) A rat model of massive rotator cuff tears. J Orthop Res 29(4):588–595

    Article  PubMed  Google Scholar 

  33. Mallon WJ, Wilson RJ, Basamania CJ (2006) The association of suprascapular neuropathy with massive rotator cuff tears: a preliminary report. J Shoulder Elbow Surg 15(4):395–398

    Article  PubMed  Google Scholar 

  34. Mannava S, Plate JF, Tuohy CJ, Seyler TM, Whitlock PW, Curl WW, Smith TL, Saul KR (2013) The science of rotator cuff tears: translating animal models to clinical recommendations using simulation analysis. Knee Surg Sports Traumatol Arthrosc 21(7):1610–1619

    Article  PubMed  Google Scholar 

  35. Mellado JM, Calmet J, Olona M, Esteve C, Camins A, Perez Del Palomar L, Gine J, Sauri A (2005) Surgically repaired massive rotator cuff tears: MRI of tendon integrity, muscle fatty degeneration, and muscle atrophy correlated with intraoperative and clinical findings. AJR Am J Roentgenol 184(5):1456–1463

    Article  CAS  PubMed  Google Scholar 

  36. Meyer DC, Lajtai G, von Rechenberg B, Pfirrmann CW, Gerber C (2006) Tendon retracts more than muscle in experimental chronic tears of the rotator cuff. J Bone Joint Surg Br 88(11):1533–1538

    Article  CAS  PubMed  Google Scholar 

  37. Montoya CP, Campbell-Hope LJ, Pemberton KD, Dunnett SB (1991) The “staircase test”: a measure of independent forelimb reaching and grasping abilities in rats. J Neurosci Methods 36(2–3):219–228

    Article  CAS  PubMed  Google Scholar 

  38. Murrell GA, Lilly EG, Davies H, Best TM, Goldner RD, Seaber AV (1992) The Achilles functional index. J Orthop Res 10(3):398–404

    Article  CAS  PubMed  Google Scholar 

  39. Perry SM, Getz CL, Soslowsky LJ (2009) Alterations in function after rotator cuff tears in an animal model. J Shoulder Elbow Surg 18(2):296–304

    Article  PubMed Central  PubMed  Google Scholar 

  40. Prut L, Belzung C (2003) The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review. Eur J Pharmacol 463(1–3):3–33

    Article  CAS  PubMed  Google Scholar 

  41. Rubino LJ, Stills HF Jr, Sprott DC, Crosby LA (2007) Fatty infiltration of the torn rotator cuff worsens over time in a rabbit model. Arthroscopy 23(7):717–722

    Article  PubMed  Google Scholar 

  42. Safran O, Derwin KA, Powell K, Iannotti JP (2005) Changes in rotator cuff muscle volume, fat content, and passive mechanics after chronic detachment in a canine model. J Bone Joint Surg Am 87(12):2662–2670

    Article  PubMed  Google Scholar 

  43. Soslowsky LJ, Carpenter JE, DeBano CM, Banerji I, Moalli MR (1996) Development and use of an animal model for investigations on rotator cuff disease. J Shoulder Elbow Surg 5(5):383–392

    Article  CAS  PubMed  Google Scholar 

  44. Sousa N, Almeida OF, Wotjak CT (2006) A hitchhiker’s guide to behavioral analysis in laboratory rodents. Genes Brain Behav 5(Suppl 2):5–24

    Article  PubMed  Google Scholar 

  45. Tauro JC (2006) Stiffness and rotator cuff tears: incidence, arthroscopic findings, and treatment results. Arthroscopy 22(6):581–586

    Article  PubMed  Google Scholar 

  46. Thomazeau H, Rolland Y, Lucas C, Duval JM, Langlais F (1996) Atrophy of the supraspinatus belly. Assessment by MRI in 55 patients with rotator cuff pathology. Acta Orthop Scand 67(3):264–268

    Article  CAS  PubMed  Google Scholar 

  47. Van Zutphen LFM, Baumans V, Beynen A (2001) Principles of laboratory animal science. Elsevier, Amsterdam

    Google Scholar 

  48. Warner JP, Krushell RJ, Masquelet A, Gerber C (1992) Anatomy and relationships of the suprascapular nerve: anatomical constraints to mobilization of the supraspinatus and infraspinatus muscles in the management of massive rotator-cuff tears. J Bone Joint Surg Am 74(1):36–45

    CAS  PubMed  Google Scholar 

  49. Zingg PO, Jost B, Sukthankar A, Buhler M, Pfirrmann CW, Gerber C (2007) Clinical and structural outcomes of nonoperative management of massive rotator cuff tears. J Bone Joint Surg Am 89(9):1928–1934

    Article  CAS  PubMed  Google Scholar 

  50. Zumstein MA, Jost B, Hempel J, Hodler J, Gerber C (2008) The clinical and structural long-term results of open repair of massive tears of the rotator cuff. J Bone Joint Surg Am 90(11):2423–2431

    Article  PubMed  Google Scholar 

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Acknowledgments

Portuguese Foundation for Science and Technology (FCT) (FCT Development Grant to A.J. Salgado). This work was also co-funded by Programa Operacional Regional do Norte (ON.2—O Novo Norte), ao abrigo do Quadro de Referência Estratégico Nacional (QREN), através do Fundo Europeu de Desenvolvimento Regional (FEDER).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal

    N. Sevivas, S. C. Serra, F. G. Teixeira, M. M. Carvalho, N. Silva, J. Espregueira-Mendes, N. Sousa & A. J. Salgado

  2. ICVS/3B’s - PT Government Associate Laboratory, Braga, Guimarães, Portugal

    N. Sevivas, S. C. Serra, F. G. Teixeira, M. M. Carvalho, N. Silva, J. Espregueira-Mendes, N. Sousa & A. J. Salgado

  3. Orthopaedics Department, Hospital de Braga, Braga, Portugal

    N. Sevivas

  4. Clínica Espregueira-Mendes, FIFA Medical Centre of Excellence, Estádio do Dragão, Porto, Portugal

    N. Sevivas & J. Espregueira-Mendes

  5. Pathology Department, Centro Hospitalar São João, Porto, Portugal

    R. Portugal

  6. 3B’s Research Group, Biomaterials, Biodegradables and Biomimetics, Department of Polymer, Engineering, University of Minho, AvePark, Zona Industrial da Gandra, S. Cláudio do Barco 4806-909 Caldas das Taipas, Guimarães, Portugal

    J. Espregueira-Mendes

  7. Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, University of Minho, AvePark, Zona Industrial da Gandra, S. Cláudio do Barco 4806-909 Caldas das Taipas, Guimarães, Portugal

    J. Espregueira-Mendes

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  1. N. Sevivas
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  2. S. C. Serra
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  3. R. Portugal
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Sevivas, N., Serra, S.C., Portugal, R. et al. Animal model for chronic massive rotator cuff tear: behavioural and histologic analysis. Knee Surg Sports Traumatol Arthrosc 23, 608–618 (2015). https://doi.org/10.1007/s00167-014-3441-3

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