Skip to main content
Erschienen in: Knee Surgery, Sports Traumatology, Arthroscopy 10/2011

01.10.2011 | Shoulder

Expression of matrix metalloproteinases 1, 3, and 9 in differing extents of tendon retraction in the torn rotator cuff

verfasst von: Stefan Lakemeier, Juliane Braun, Turgay Efe, Christian Foelsch, Eleni Archontidou-Aprin, Susanne Fuchs-Winkelmann, Juergen R. J. Paletta, Markus D. Schofer

Erschienen in: Knee Surgery, Sports Traumatology, Arthroscopy | Ausgabe 10/2011

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Differing extents of tendon retraction are found in full-thickness rotator cuff tears. The pathophysiologic context of tendon degeneration and the extent of tendon retraction are unclear. Tendon integrity depends on the extracellular matrix, which is regulated by matrix metalloproteinases (MMP). It is unknown which enzymes play a role in tendon degeneration. The hypotheses are that (1) the expression of MMPs 1, 3, and 9 is altered in the torn rotator cuff when compared with healthy tendon samples; and (2) that there is a relationship between MMP expression and the extent of tendon retraction in the torn cuff.

Methods

Rotator cuff tendon samples of 33 patients with full-thickness rotator cuff tears (Bateman grade III) were harvested during reconstructive surgery. Samples were dehydrated and paraffin-embedded. Immunohistologic determination of MMP 1, 3, and 9 expression was performed by staining sample slices with MMP antibody. The extent of tendon retraction was determined intraoperatively according to Patte’s classification and patients were assigned to 4 groups (control group, and by tendon retraction grade Patte I-III). The control group consisted of six healthy tendon samples.

Results

Expression of MMPs 1 and 9 was significantly higher in torn cuff samples than in healthy tendons whereas MMP 3 expression was significantly decreased (P < 0.05). MMP 9 expression significantly increased with rising extent of tendon retraction in the torn cuff (P < 0.05). No significant association was found between expression of MMPs 1 and 3 and the rising extent of tendon retraction by Patte’s classification.

Conclusion

Elevated expression of MMPs 1 and 9 as well as decreased MMP 3 expression can be detected in torn rotator cuff tendon tissue. There is a significant association between the extent of tendon retraction and MMP 9 expression. The results of this study give evidence that early surgical treatment of small and partial-thickness rotator cuff tears is required.
Literatur
1.
Zurück zum Zitat Alfredson H (2005) The chronic painful Achilles and patellar tendon: research on basic biology and treatment. Scand J Med Sci Sports 15:252–259PubMedCrossRef Alfredson H (2005) The chronic painful Achilles and patellar tendon: research on basic biology and treatment. Scand J Med Sci Sports 15:252–259PubMedCrossRef
2.
Zurück zum Zitat Andarawis-Puri N, Ricchetti ET, Soslowsky LJ (2009) Rotator cuff tendon strain correlates with tear propagation. J Biomech 42:158–163PubMedCrossRef Andarawis-Puri N, Ricchetti ET, Soslowsky LJ (2009) Rotator cuff tendon strain correlates with tear propagation. J Biomech 42:158–163PubMedCrossRef
3.
Zurück zum Zitat Asundi KR, Rempel DM (2008) Cyclic loading inhibits expression of MMP-3 but not MMP-1 in an in vitro rabbit flexor tendon model. Clin Biomech (Bristol, Avon) 23:117–121CrossRef Asundi KR, Rempel DM (2008) Cyclic loading inhibits expression of MMP-3 but not MMP-1 in an in vitro rabbit flexor tendon model. Clin Biomech (Bristol, Avon) 23:117–121CrossRef
4.
Zurück zum Zitat Bateman JE (1963) The diagnosis and treatment of ruptures of the rotator cuff. Surg Clin North Am 43:1523–1530PubMed Bateman JE (1963) The diagnosis and treatment of ruptures of the rotator cuff. Surg Clin North Am 43:1523–1530PubMed
5.
Zurück zum Zitat Bedi A, Fox AJ, Kovacevic D, Deng XH, Warren RF, Rodeo SA (2010) Doxycycline-mediated inhibition of matrix metalloproteinases improves healing after rotator cuff repair. Am J Sports Med 38:308–317PubMedCrossRef Bedi A, Fox AJ, Kovacevic D, Deng XH, Warren RF, Rodeo SA (2010) Doxycycline-mediated inhibition of matrix metalloproteinases improves healing after rotator cuff repair. Am J Sports Med 38:308–317PubMedCrossRef
6.
Zurück zum Zitat Budoff JE, Rodin D, Ochiai D, Nirschl RP (2005) Arthroscopic rotator cuff debridement without decompression for the treatment of tendinosis. Arthroscopy 21:1081–1089PubMedCrossRef Budoff JE, Rodin D, Ochiai D, Nirschl RP (2005) Arthroscopic rotator cuff debridement without decompression for the treatment of tendinosis. Arthroscopy 21:1081–1089PubMedCrossRef
7.
Zurück zum Zitat Chong AK, Ang AD, Goh JC, Hui JH, Lim AY, Lee EH, Lim BH (2007) Bone marrow-derived mesenchymal stem cells influence early tendon-healing in a rabbit achilles tendon model. J Bone Joint Surg Am 89:74–81PubMedCrossRef Chong AK, Ang AD, Goh JC, Hui JH, Lim AY, Lee EH, Lim BH (2007) Bone marrow-derived mesenchymal stem cells influence early tendon-healing in a rabbit achilles tendon model. J Bone Joint Surg Am 89:74–81PubMedCrossRef
8.
Zurück zum Zitat Dudhia J, Scott CM, Draper ER, Heinegard D, Pitsillides AA, Smith RK (2007) Aging enhances a mechanically-induced reduction in tendon strength by an active process involving matrix metalloproteinase activity. Aging Cell 6:547–556PubMedCrossRef Dudhia J, Scott CM, Draper ER, Heinegard D, Pitsillides AA, Smith RK (2007) Aging enhances a mechanically-induced reduction in tendon strength by an active process involving matrix metalloproteinase activity. Aging Cell 6:547–556PubMedCrossRef
9.
Zurück zum Zitat Fu SC, Chan BP, Wang W, Pau HM, Chan KM, Rolf CG (2002) Increased expression of matrix metalloproteinase 1 (MMP1) in 11 patients with patellar tendinosis. Acta Orthop Scand 73:658–662PubMedCrossRef Fu SC, Chan BP, Wang W, Pau HM, Chan KM, Rolf CG (2002) Increased expression of matrix metalloproteinase 1 (MMP1) in 11 patients with patellar tendinosis. Acta Orthop Scand 73:658–662PubMedCrossRef
10.
Zurück zum Zitat Fuchs S, Skwara A, Bloch M, Dankbar B (2004) Differential induction and regulation of matrix metalloproteinases in osteoarthritic tissue and fluid synovial fibroblasts. Osteoarthr Cartil 12:409–418PubMedCrossRef Fuchs S, Skwara A, Bloch M, Dankbar B (2004) Differential induction and regulation of matrix metalloproteinases in osteoarthritic tissue and fluid synovial fibroblasts. Osteoarthr Cartil 12:409–418PubMedCrossRef
11.
Zurück zum Zitat Gohlke F (1993) Ultrasonographic appearance of the rotator cuff in elderly subjects. Orthopade 22:288–293PubMed Gohlke F (1993) Ultrasonographic appearance of the rotator cuff in elderly subjects. Orthopade 22:288–293PubMed
12.
Zurück zum Zitat Gulotta LV, Kovacevic D, Montgomery S, Ehteshami JR, Packer JD, Rodeo SA (2010) Stem cells genetically modified with the developmental gene MT1-MMP improve regeneration of the supraspinatus tendon-to-bone insertion site. Am J Sports Med 38:1429–1437PubMedCrossRef Gulotta LV, Kovacevic D, Montgomery S, Ehteshami JR, Packer JD, Rodeo SA (2010) Stem cells genetically modified with the developmental gene MT1-MMP improve regeneration of the supraspinatus tendon-to-bone insertion site. Am J Sports Med 38:1429–1437PubMedCrossRef
13.
Zurück zum Zitat Gwilym SE, Watkins B, Cooper CD, Harvie P, Auplish S, Pollard TC, Rees JL, Carr AJ (2009) Genetic influences in the progression of tears of the rotator cuff. J Bone Joint Surg Br 91:915–917PubMedCrossRef Gwilym SE, Watkins B, Cooper CD, Harvie P, Auplish S, Pollard TC, Rees JL, Carr AJ (2009) Genetic influences in the progression of tears of the rotator cuff. J Bone Joint Surg Br 91:915–917PubMedCrossRef
14.
Zurück zum Zitat Ireland D, Harrall R, Curry V, Holloway G, Hackney R, Hazleman B, Riley G (2001) Multiple changes in gene expression in chronic human Achilles tendinopathy. Matrix Biol 20:159–169PubMedCrossRef Ireland D, Harrall R, Curry V, Holloway G, Hackney R, Hazleman B, Riley G (2001) Multiple changes in gene expression in chronic human Achilles tendinopathy. Matrix Biol 20:159–169PubMedCrossRef
15.
Zurück zum Zitat Irie T, Takahata M, Majima T, Abe Y, Komatsu M, Iwasaki N, Minami A (2010) Effect of selective estrogen receptor modulator/raloxifene analogue on proliferation and collagen metabolism of tendon fibroblast. Connect Tissue Res 51:179–187PubMedCrossRef Irie T, Takahata M, Majima T, Abe Y, Komatsu M, Iwasaki N, Minami A (2010) Effect of selective estrogen receptor modulator/raloxifene analogue on proliferation and collagen metabolism of tendon fibroblast. Connect Tissue Res 51:179–187PubMedCrossRef
16.
Zurück zum Zitat Jones GC, Corps AN, Pennington CJ, Clark IM, Edwards DR, Bradley MM, Hazleman BL, Riley GP (2006) Expression profiling of metalloproteinases and tissue inhibitors of metalloproteinases in normal and degenerate human achilles tendon. Arthritis Rheum 54:832–842PubMedCrossRef Jones GC, Corps AN, Pennington CJ, Clark IM, Edwards DR, Bradley MM, Hazleman BL, Riley GP (2006) Expression profiling of metalloproteinases and tissue inhibitors of metalloproteinases in normal and degenerate human achilles tendon. Arthritis Rheum 54:832–842PubMedCrossRef
17.
Zurück zum Zitat Karaoglu S, Celik C, Korkusuz P (2009) The effects of bone marrow or periosteum on tendon-to-bone tunnel healing in a rabbit model. Knee Surg Sports Traumatol Arthrosc 17:170–178PubMedCrossRef Karaoglu S, Celik C, Korkusuz P (2009) The effects of bone marrow or periosteum on tendon-to-bone tunnel healing in a rabbit model. Knee Surg Sports Traumatol Arthrosc 17:170–178PubMedCrossRef
18.
Zurück zum Zitat Kjaer M (2004) Role of extracellular matrix in adaptation of tendon and skeletal muscle to mechanical loading. Physiol Rev 84:649–698PubMedCrossRef Kjaer M (2004) Role of extracellular matrix in adaptation of tendon and skeletal muscle to mechanical loading. Physiol Rev 84:649–698PubMedCrossRef
19.
Zurück zum Zitat Lehmann LJ, Schollmeyer A, Stoeve J, Scharf HP (2009) Biochemical analysis of the synovial fluid of the shoulder joint in patients with and without rotator cuff tears. Z Orthop Unfall 148:90–94PubMedCrossRef Lehmann LJ, Schollmeyer A, Stoeve J, Scharf HP (2009) Biochemical analysis of the synovial fluid of the shoulder joint in patients with and without rotator cuff tears. Z Orthop Unfall 148:90–94PubMedCrossRef
21.
Zurück zum Zitat Lewis JS (2009) Rotator cuff tendinopathy/subacromial impingement syndrome: is it time for a new method of assessment? Br J Sports Med 43:259–264PubMedCrossRef Lewis JS (2009) Rotator cuff tendinopathy/subacromial impingement syndrome: is it time for a new method of assessment? Br J Sports Med 43:259–264PubMedCrossRef
22.
Zurück zum Zitat Lewis JS, Sandford FM (2009) Rotator cuff tendinopathy: is there a role for polyunsaturated fatty acids and antioxidants? J Hand Ther 22:49–55 quiz 56PubMedCrossRef Lewis JS, Sandford FM (2009) Rotator cuff tendinopathy: is there a role for polyunsaturated fatty acids and antioxidants? J Hand Ther 22:49–55 quiz 56PubMedCrossRef
23.
Zurück zum Zitat Liu X, Han Q, Sun R, Li Z (2008) Dexamethasone regulation of matrix metalloproteinase expression in experimental pneumococcal meningitis. Brain Res 1207:237–243PubMedCrossRef Liu X, Han Q, Sun R, Li Z (2008) Dexamethasone regulation of matrix metalloproteinase expression in experimental pneumococcal meningitis. Brain Res 1207:237–243PubMedCrossRef
24.
Zurück zum Zitat Lo IK, Marchuk LL, Hollinshead R, Hart DA, Frank CB (2004) Matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase mRNA levels are specifically altered in torn rotator cuff tendons. Am J Sports Med 32:1223–1229PubMedCrossRef Lo IK, Marchuk LL, Hollinshead R, Hart DA, Frank CB (2004) Matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase mRNA levels are specifically altered in torn rotator cuff tendons. Am J Sports Med 32:1223–1229PubMedCrossRef
25.
Zurück zum Zitat Lohr JF, Uhthoff HK (1990) The microvascular pattern of the supraspinatus tendon. Clin Orthop Relat Res 254:35–38PubMed Lohr JF, Uhthoff HK (1990) The microvascular pattern of the supraspinatus tendon. Clin Orthop Relat Res 254:35–38PubMed
26.
Zurück zum Zitat Matsui Y, Maeda M, Nakagami W, Iwata H (1998) The involvement of matrix metalloproteinases and inflammation in lumbar disc herniation. Spine (Phila Pa 1976) 23:863–868 discussion 868-869CrossRef Matsui Y, Maeda M, Nakagami W, Iwata H (1998) The involvement of matrix metalloproteinases and inflammation in lumbar disc herniation. Spine (Phila Pa 1976) 23:863–868 discussion 868-869CrossRef
27.
Zurück zum Zitat Neer CS II (1972) Anterior acromioplasty for the chronic impingement syndrome in the shoulder: a preliminary report. J Bone Joint Surg Am 54:41–50PubMed Neer CS II (1972) Anterior acromioplasty for the chronic impingement syndrome in the shoulder: a preliminary report. J Bone Joint Surg Am 54:41–50PubMed
28.
Zurück zum Zitat Nho SJ, Yadav H, Shindle MK, Macgillivray JD (2008) Rotator cuff degeneration: etiology and pathogenesis. Am J Sports Med 36:987–993PubMedCrossRef Nho SJ, Yadav H, Shindle MK, Macgillivray JD (2008) Rotator cuff degeneration: etiology and pathogenesis. Am J Sports Med 36:987–993PubMedCrossRef
29.
Zurück zum Zitat Pasternak B, Aspenberg P (2009) Metalloproteinases and their inhibitors-diagnostic and therapeutic opportunities in orthopedics. Acta Orthop 80:693–703PubMedCrossRef Pasternak B, Aspenberg P (2009) Metalloproteinases and their inhibitors-diagnostic and therapeutic opportunities in orthopedics. Acta Orthop 80:693–703PubMedCrossRef
30.
Zurück zum Zitat Patte D (1990) Classification of rotator cuff lesions. Clin Orthop Relat Res 254:81–86PubMed Patte D (1990) Classification of rotator cuff lesions. Clin Orthop Relat Res 254:81–86PubMed
31.
Zurück zum Zitat Pauly S, Klatte F, Strobel C, Schmidmaier G, Greiner S, Scheibel M, Wildemann B (2010) Characterization of tendon cell cultures of the human rotator cuff. Eur Cell Mater 20:84–97PubMed Pauly S, Klatte F, Strobel C, Schmidmaier G, Greiner S, Scheibel M, Wildemann B (2010) Characterization of tendon cell cultures of the human rotator cuff. Eur Cell Mater 20:84–97PubMed
32.
Zurück zum Zitat Perry SM, Getz CL, Soslowsky LJ (2009) After rotator cuff tears, the remaining (intact) tendons are mechanically altered. J Shoulder Elbow Surg 18:52–57PubMedCrossRef Perry SM, Getz CL, Soslowsky LJ (2009) After rotator cuff tears, the remaining (intact) tendons are mechanically altered. J Shoulder Elbow Surg 18:52–57PubMedCrossRef
33.
Zurück zum Zitat Raleigh SM, van der Merwe L, Ribbans WJ, Smith RK, Schwellnus MP, Collins M (2009) Variants within the MMP3 gene are associated with Achilles tendinopathy: possible interaction with the COL5A1 gene. Br J Sports Med 43:514–520PubMedCrossRef Raleigh SM, van der Merwe L, Ribbans WJ, Smith RK, Schwellnus MP, Collins M (2009) Variants within the MMP3 gene are associated with Achilles tendinopathy: possible interaction with the COL5A1 gene. Br J Sports Med 43:514–520PubMedCrossRef
34.
Zurück zum Zitat Riley G (2004) The pathogenesis of tendinopathy. A molecular perspective. Rheumatology (Oxford) 43:131–142CrossRef Riley G (2004) The pathogenesis of tendinopathy. A molecular perspective. Rheumatology (Oxford) 43:131–142CrossRef
35.
Zurück zum Zitat Riley G (2008) Tendinopathy–from basic science to treatment. Nat Clin Pract Rheumatol 4:82–89PubMedCrossRef Riley G (2008) Tendinopathy–from basic science to treatment. Nat Clin Pract Rheumatol 4:82–89PubMedCrossRef
36.
Zurück zum Zitat Riley GP (2005) Gene expression and matrix turnover in overused and damaged tendons. Scand J Med Sci Sports 15:241–251PubMedCrossRef Riley GP (2005) Gene expression and matrix turnover in overused and damaged tendons. Scand J Med Sci Sports 15:241–251PubMedCrossRef
37.
Zurück zum Zitat Schofer MD, Quante M, Peterlein CD, Timmesfeld N, Phan K, Fuchs-Winkelmann S (2009) Operative and follow-up treatment of rotator cuff tears–the current situation. Z Orthop Unfall 147:321–326PubMedCrossRef Schofer MD, Quante M, Peterlein CD, Timmesfeld N, Phan K, Fuchs-Winkelmann S (2009) Operative and follow-up treatment of rotator cuff tears–the current situation. Z Orthop Unfall 147:321–326PubMedCrossRef
38.
Zurück zum Zitat Tajana MS, Murena L, Valli F, Passi A, Grassi FA (2009) Correlations between biochemical markers in the synovial fluid and severity of rotator cuff disease. Chir Organi Mov 93(Suppl 1):S41–S48PubMed Tajana MS, Murena L, Valli F, Passi A, Grassi FA (2009) Correlations between biochemical markers in the synovial fluid and severity of rotator cuff disease. Chir Organi Mov 93(Suppl 1):S41–S48PubMed
39.
Zurück zum Zitat Tondreau T, Meuleman N, Stamatopoulos B, De Bruyn C, Delforge A, Dejeneffe M, Martiat P, Bron D, Lagneaux L (2009) In vitro study of matrix metalloproteinase/tissue inhibitor of metalloproteinase production by mesenchymal stromal cells in response to inflammatory cytokines: the role of their migration in injured tissues. Cytotherapy 11:559–569PubMedCrossRef Tondreau T, Meuleman N, Stamatopoulos B, De Bruyn C, Delforge A, Dejeneffe M, Martiat P, Bron D, Lagneaux L (2009) In vitro study of matrix metalloproteinase/tissue inhibitor of metalloproteinase production by mesenchymal stromal cells in response to inflammatory cytokines: the role of their migration in injured tissues. Cytotherapy 11:559–569PubMedCrossRef
40.
Zurück zum Zitat Tsai WC, Hsu CC, Chang HN, Lin YC, Lin MS, Pang JH (2010) Ibuprofen upregulates expressions of matrix metalloproteinase-1, -8, -9, and -13 without affecting expressions of types I and III collagen in tendon cells. J Orthop Res 28:487–491PubMed Tsai WC, Hsu CC, Chang HN, Lin YC, Lin MS, Pang JH (2010) Ibuprofen upregulates expressions of matrix metalloproteinase-1, -8, -9, and -13 without affecting expressions of types I and III collagen in tendon cells. J Orthop Res 28:487–491PubMed
41.
Zurück zum Zitat Voloshin I, Gelinas J, Maloney MD, O’Keefe RJ, Bigliani LU, Blaine TA (2005) Proinflammatory cytokines and metalloproteases are expressed in the subacromial bursa in patients with rotator cuff disease. Arthroscopy 21:1076PubMed Voloshin I, Gelinas J, Maloney MD, O’Keefe RJ, Bigliani LU, Blaine TA (2005) Proinflammatory cytokines and metalloproteases are expressed in the subacromial bursa in patients with rotator cuff disease. Arthroscopy 21:1076PubMed
42.
Zurück zum Zitat Yamaguchi K, Ditsios K, Middleton WD, Hildebolt CF, Galatz LM, Teefey SA (2006) The demographic and morphological features of rotator cuff disease. A comparison of asymptomatic and symptomatic shoulders. J Bone Joint Surg Am 88:1699–1704PubMedCrossRef Yamaguchi K, Ditsios K, Middleton WD, Hildebolt CF, Galatz LM, Teefey SA (2006) The demographic and morphological features of rotator cuff disease. A comparison of asymptomatic and symptomatic shoulders. J Bone Joint Surg Am 88:1699–1704PubMedCrossRef
43.
Zurück zum Zitat Yoshihara Y, Hamada K, Nakajima T, Fujikawa K, Fukuda H (2001) Biochemical markers in the synovial fluid of glenohumeral joints from patients with rotator cuff tear. J Orthop Res 19:573–579PubMedCrossRef Yoshihara Y, Hamada K, Nakajima T, Fujikawa K, Fukuda H (2001) Biochemical markers in the synovial fluid of glenohumeral joints from patients with rotator cuff tear. J Orthop Res 19:573–579PubMedCrossRef
Metadaten
Titel
Expression of matrix metalloproteinases 1, 3, and 9 in differing extents of tendon retraction in the torn rotator cuff
verfasst von
Stefan Lakemeier
Juliane Braun
Turgay Efe
Christian Foelsch
Eleni Archontidou-Aprin
Susanne Fuchs-Winkelmann
Juergen R. J. Paletta
Markus D. Schofer
Publikationsdatum
01.10.2011
Verlag
Springer-Verlag
Erschienen in
Knee Surgery, Sports Traumatology, Arthroscopy / Ausgabe 10/2011
Print ISSN: 0942-2056
Elektronische ISSN: 1433-7347
DOI
https://doi.org/10.1007/s00167-010-1367-y

Weitere Artikel der Ausgabe 10/2011

Knee Surgery, Sports Traumatology, Arthroscopy 10/2011 Zur Ausgabe

Arthropedia

Grundlagenwissen der Arthroskopie und Gelenkchirurgie. Erweitert durch Fallbeispiele, Videos und Abbildungen. 
» Jetzt entdecken

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Arthroskopie kann Knieprothese nicht hinauszögern

25.04.2024 Gonarthrose Nachrichten

Ein arthroskopischer Eingriff bei Kniearthrose macht im Hinblick darauf, ob und wann ein Gelenkersatz fällig wird, offenbar keinen Unterschied.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Ärztliche Empathie hilft gegen Rückenschmerzen

23.04.2024 Leitsymptom Rückenschmerzen Nachrichten

Personen mit chronischen Rückenschmerzen, die von einfühlsamen Ärzten und Ärztinnen betreut werden, berichten über weniger Beschwerden und eine bessere Lebensqualität.

Update Orthopädie und Unfallchirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.