Aesthetic Plastic Surgery

, Volume 33, Issue 4, pp 555–562 | Cite as

Effect of Tissue Inhibitors of Metalloproteinases and Matrix Metalloproteinases on Capsular Formation Around Smooth and Textured Silicone Gel Implants

  • Dietmar Ulrich
  • Franziska Ulrich
  • Norbert Pallua
  • Marita Eisenmann-Klein
Original Article

Abstract

Background

Capsular contracture is one of the most distressing complications after cosmetic breast augmentation. Evidence suggests that matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) may play a key role in the onset or progression of several fibrotic disorders. In this study we used quantitative reverse-transcription PCR methodology to profile the expression of TIMP-1, TIMP-2, MMP-2, and MMP-9 in the tissue of patients with capsular contracture after breast augmentation with smooth and textured silicone breast implants.

Methods

The study included 20 female patients (average age = 37 ± 15 years) with capsular contracture after bilateral subglandular cosmetic breast augmentation with smooth silicone implants. Ten patients developed grade II capsule contracture, 8 grade III contracture, and 1 grade IV contracture. Twenty other female patients (average age = 41 ± 9 years) with capsular contracture after breast augmentation with textured silicone implants were also included (Baker grade II = 10 patients, grade III = 8, grade IV = 2). Expression of mRNA in capsular tissue was calculated using a relative quantification method (Pfaffl). Statistical analysis was performed using the Mann-Whitney test. The level of significance was considered to be p < 0.05.

Results

The expression of MMP-2 was significantly increased in tissue of patients with textured implants and capsular contracture grades II and III/IV in comparison to grade I (p < 0.05). In comparison to grade I, the capsular tissue from patients with Baker II and III/IV fibrosis showed a significant increase for TIMP-1 and TIMP-2 (p < 0.05) in both smooth and textured silicone implants. The expression was significantly higher in tissue from patients with severe contracture (Baker III/IV) and smooth silicone implants compared with that in tissue from patients with textured implants (p < 0.05).

Conclusion

The decrease in MMP-to-TIMP expression can cause increased synthesis and deposition of collagen surrounding alloplastic breast implants, leading to a profibrotic state. The higher expression of TIMPs in capsular tissue of patients with smooth silicone gel implants might be a reason for the observed higher rates of capsular contracture. In the future, a nonoperative treatment that decreases TIMPs but increases the activity of MMPs may be an appropriate therapy for patients with capsular contracture.

Keywords

Breast augmentation Smooth silicone implants Textured silicone implants Capsular contracture Matrix metalloproteinases Tissue inhibitors of metalloproteinases 

Notes

Disclosure

The authors hereby certify that, to the best of their knowledge, no financial support or benefits have been received by any of them, by any member of their immediate families, or by any individual or entity with whom or with which they have a significant relationship from any commercial source that is related directly or indirectly to the scientific work that is reported on in the article.

References

  1. 1.
    Bostwick J (2000) Tissue expansion reconstruction. In: Bostwick J (ed) Plastic and reconstructive breast surgery, vol 2. Quality Medical Publishing, St. Louis, pp 811–866Google Scholar
  2. 2.
    Brody GS (1997) On the safety of breast implants. Plast Reconstr Surg 100:1314–1321PubMedCrossRefGoogle Scholar
  3. 3.
    Burkhardt BR (1988) Capsular contracture: hard breasts, soft data. Clin Plast Surg 15:521–532PubMedGoogle Scholar
  4. 4.
    Sevin A, Sevin K, Senen D et al (2006) Augmentation mammaplasty: retrospective analysis of 210 cases. Aesthetic Plast Surg 30:651–654PubMedCrossRefGoogle Scholar
  5. 5.
    Spear Sl, Murphy DK, Slicton A et al (2007) Inamed silicone breast implant core study results at 6 years. Plast Reconstr Surg 120:8S–16SPubMedCrossRefGoogle Scholar
  6. 6.
    Ersek R (1991) Rate and incidence of capsular contracture: a comparison of smooth and textured silicone double lumen breast prosthesis. Plast Reconstr Surg 87:879–884PubMedCrossRefGoogle Scholar
  7. 7.
    Freedman AM, Jackson IT (1989) Infections in breast implants. Infect Dis Clin North Am 3:275–287PubMedGoogle Scholar
  8. 8.
    Pittet B, Montandon D, Pittet D (2005) Infection in breast implants. Lancet Infect Dis 5:94–106PubMedGoogle Scholar
  9. 9.
    Schreml S, Heine N, Eisenmann-Klein M, Prantl L (2007) Bacterial colonization is of major relevance for high-grade capsular contracture after augmentation mammaplasty. Ann Plast Surg 59:126–130PubMedCrossRefGoogle Scholar
  10. 10.
    Vistnes LM, Ksander GA, Kosek J (1978) Study of encapsulation of silicone rubber implant in animals: a foreign-body reaction. Plast Reconstr Surg 62:580–588PubMedGoogle Scholar
  11. 11.
    Baker JL Jr, Chandler ML, LeVier RR (1981) Occurrence and activity of myofibroblasts in human capsular tissue surrounding mammary implants. Plast Reconstr Surg 68:905–912PubMedCrossRefGoogle Scholar
  12. 12.
    Lossing C, Hansson HA (1993) Peptide growth factors and myofibroblasts in capsules around human breast implants. Plast Reconstr Surg 91:1277PubMedCrossRefGoogle Scholar
  13. 13.
    Embrey M, Adams EE, Cunningham B, Peters W, Young VL, Carlo GL (1999) A review of the literature on the aetiology of capsular contracture and a pilot study to determine the outcome of capsular contracture interventions. Aesthetic Plast Surg 23:197–206PubMedCrossRefGoogle Scholar
  14. 14.
    Gabriel SE, Woods JE, O’Fallon WM et al (1997) Complications leading to surgery after breast implantation. N Engl J Med 336:677–682PubMedCrossRefGoogle Scholar
  15. 15.
    Gampper TJ, Khoury H, Gottlieb W, Morgan RF (2007) Silicone gel implants in breast augmentation and reconstruction. Ann Plast Surg 59:581–590PubMedCrossRefGoogle Scholar
  16. 16.
    Vasquez B, Given KS, Houston C (1987) Breast augmentation: a review of subglandular and submuscular implantation. Aesthetic Plast Surg 11:101–105CrossRefGoogle Scholar
  17. 17.
    Mott JD, Werb Z (2004) Regulation of matrix biology by matrix metalloproteinases. Curr Opin Cell Biol 16:558–564PubMedCrossRefGoogle Scholar
  18. 18.
    Visse R, Nagase H (2003) Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res 92:827–839PubMedCrossRefGoogle Scholar
  19. 19.
    Nagase H, Woessner JF (1999) Matrix metalloproteinases. J Biol Chem 274:21491–21494PubMedCrossRefGoogle Scholar
  20. 20.
    Brinckerhoff CE, Matrisian LM (2002) Matrix metalloproteinases: a tail of a frog that became a prince. Nat Rev Mol Cell Biol 3:207–214PubMedCrossRefGoogle Scholar
  21. 21.
    Nagase H, Visse R, Murphy G (2006) Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res 69:562–573PubMedCrossRefGoogle Scholar
  22. 22.
    Massova I, Kotra LP, Fridman R, Mobashery S (1998) Matrix metalloproteinases: structures, evolution, and diversification. FASEB J 12:1075–1095PubMedGoogle Scholar
  23. 23.
    Patterson ML, Atkinson SJ, Knäuper V, Murphy G (2003) Specific collagenolysis by gelatinase A, MMP-2, is determined by the hemopexin domain and not the fibronectin-like domain. FEBS Lett 503:158–162CrossRefGoogle Scholar
  24. 24.
    Brew K, Dinakarpandian D, Nagase H (2002) Tissue inhibitors of metalloproteinases: evolution, structure and function. Biochim Biophys Acta 1477:267–283Google Scholar
  25. 25.
    Ravanti L, Kahari VM (2001) Matrix metalloproteinases in wound repair. Int J Mol Med 6:391–407Google Scholar
  26. 26.
    Reynolds JJ (1996) Collagenases and tissue inhibitors of metalloproteinases: a functional balance in tissue degradation. Oral Dis 2:70–76PubMedGoogle Scholar
  27. 27.
    Forbes JM, Thallas V, Thomas MC et al (2003) The breakdown of preexisting advanced glycation end products is associated with reduced renal fibrosis in experimental diabetes. FASEB J 17:1762–1764PubMedGoogle Scholar
  28. 28.
    Lichtinghagen R, Michels D, Haberkorn CI et al (2001) Matrix metalloproteinase MMP-2, MMP-7, and tissue inhibitor of metalloproteinase are closely related to fibroproliferative process in the liver during chronic hepatitis C. J Hepatol 34:239–247PubMedCrossRefGoogle Scholar
  29. 29.
    Ramadori G, Knittel T, Saile B (1998) Fibrosis and altered matrix synthesis. Digestion 59:372–375PubMedCrossRefGoogle Scholar
  30. 30.
    Unemori EN, Pickford LB, Salles AL et al (1996) Relaxin induces an extracellular matrix-degrading phenotype in human lung fibroblasts in vitro and inhibits lung fibrosis in a murine model in vivo. J Clin Invest 98:2739–2745PubMedCrossRefGoogle Scholar
  31. 31.
    Ulrich D, Hrynyschyn K, Pallua N (2003) Matrix metalloproteinases and tissue inhibitors of metalloproteinase in sera and tissue of patients with Dupuytren’s disease. Plast Reconstr Surg 112:1279–1286PubMedCrossRefGoogle Scholar
  32. 32.
    Ulrich D, Noah EM, von Heimburg D, Pallua N (2003) TIMP-1, MMP-2, MMP-9, and PIIINP as serum markers for skin fibrosis in patients following severe burn trauma. Plast Reconstr Surg 111:1423–1431PubMedCrossRefGoogle Scholar
  33. 33.
    Handel N, Jensen JA, Black Q et al (1995) The fate of breast implants: a critical analysis of complications and outcomes. Plast Reconstr Surg 96:1521–1533PubMedCrossRefGoogle Scholar
  34. 34.
    Collis N, Coleman D, Foo IT, Sharpe DT (2000) Ten-year review of a prospective randomized controlled trial of textured versus smooth subglandular silicone gel breast implants. Plast Reconstr Surg 106:786–791PubMedCrossRefGoogle Scholar
  35. 35.
    Hakelius L, Ohlsen L (1997) Tendency to capsular contracture around smooth and textured gel-filled silicone mammary implants: a 5-year follow-up. Plast Reconstr Surg 100:1566–1569PubMedCrossRefGoogle Scholar
  36. 36.
    Malata CM, Feldberg L, Coleman DJ, Foo IT, Sharpe DT (1997) Textured or smooth implants for breast augmentation? Three year follow-up of a prospective randomized controlled trial. Br J Plast Surg 50:99–105PubMedCrossRefGoogle Scholar
  37. 37.
    Wong S, Tan S (2006) Capsular contracture in subglandular breast augmentation with textured versus smooth breast implants: a systemic review. Plast Reconstr Surg 118:1224–1236PubMedCrossRefGoogle Scholar
  38. 38.
    Mao Sl, Gao WC (2008) Capsular contracture in breast augmentation with textured versus smooth mammary implants: a systematic review. Zhonghua Zheng Xing Wai Ke Za Zhi 24:71–74Google Scholar
  39. 39.
    Mahler D, Hauben DJ (1982) Retromammary versus retropectoral breast augmentation: a comparative study. Ann Plast Surg 8:370–374PubMedCrossRefGoogle Scholar
  40. 40.
    Maxwell GP, Lugston PA (1997) Management of complications following augmentation mammaplasty. In: Georgeade GS, Riefkohl R, Levin LS (eds) Georgeade plastic, maxillofacial and reconstructive surgery, 3rd edn. Williams & Wilkins, BaltimoreGoogle Scholar
  41. 41.
    Puckett CL, Croll GH, Reichel CA, Concannon MJ (1987) A critical look at capsule contracture in subglandular versus subpectoral mammary augmentation. Aesthetic Plast Surg 11:23–28PubMedCrossRefGoogle Scholar
  42. 42.
    Vu TH, Werb Z (2000) Matrix metalloproteinases: effectors of development and normal physiology. Genes Dev 14:2123–2133PubMedCrossRefGoogle Scholar
  43. 43.
    Smeets R, Ulrich D, Unglaub F, Wöltje M, Pallua N (2008) Effect of regenerated cellulose/collagen matrix on proteases in wound exudate of patients with chronic venous ulceration. Int Wound J 5:195–203PubMedCrossRefGoogle Scholar
  44. 44.
    Wolfram D, Oberreiter B, Mayerl C et al (2008) Altered systemic serologic parameters in patients with silicone mammary implants. Immunol Lett 118:96–100PubMedCrossRefGoogle Scholar
  45. 45.
    Ulrich D, Lichtenegger F, Eblenkamp M, Repper D, Pallua N (2004) Matrix metalloproteinases, tissue inhibitors of metalloproteinases, aminoterminal propeptide of procollagen type III, and hyaluronan in sera and tissue of patients with capsular contracture after augmentation with TRILUCENT breast implants. Plast Reconstr Surg 114:229–236PubMedCrossRefGoogle Scholar
  46. 46.
    Imai K, Hiramatsu A, Fukushima D, Pierschabacher D, Okada Y (1997) Degradation of decorin by matrix metalloproteinases: identification of the cleavage sites, kinetic analyses and transforming growth factor-β1 release. Biochem J 322:809–814PubMedGoogle Scholar
  47. 47.
    Asplund O, Gylbert L, Jurell G, Ward C (1996) Textured or smooth implants for submuscular breast augmmentation: a controlled study. Plast Reconstr Surg 97:1200–1205PubMedCrossRefGoogle Scholar
  48. 48.
    Camirand A, Doucet J (2000) Breast augmentation: teaching our patients how compression can help prevent capsular contracture. Aesthetic Plast Surg 24:221–226PubMedCrossRefGoogle Scholar
  49. 49.
    Tarlton JF, Meagher P, Brown RA et al (1998) Mechanical stress in vitro induces increased expression of MMPs 2 and 9 in excised Dupuytren’s disease tissue. J Hand Surg [Br] 23:297–302Google Scholar
  50. 50.
    Unemori EN, Beck LS, Lee WP et al (1993) Human relaxin decreases collagen accumulation in vivo in two rodent models of fibrosis. J Invest Dermatol 101:280–285PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC and International Society of Aesthetic Plastic Surgery 2009

Authors and Affiliations

  • Dietmar Ulrich
    • 1
  • Franziska Ulrich
    • 2
  • Norbert Pallua
    • 1
  • Marita Eisenmann-Klein
    • 2
  1. 1.Department of Plastic Surgery, Hand Surgery, Burn UnitUniversity Hospital, Aachen University of TechnologyAachenGermany
  2. 2.Departments of Plastic, Reconstructive, Aesthetic, and Hand SurgeryCaritas Hospital St. JosefRegensburgGermany

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