Autologous matrix-induced chondrogenesis

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The Autologous Matrix Induced chondrogenesis (AMIC) (syn. Autogenous Matrix Induced chondrogenesis) is a biological surgical procedure for the treatment and repair of damaged articular cartilage . This is a modification of microfracturing , a technique for treating small cartilage defects in which a two-layer collagen I / III membrane is also applied. The acronym AMIC is a brand name used by Ed. Geistlich Söhne AG owns the rights.

AMIC brings about pain relief and restoration of joint function and is ultimately intended to enable a complete recovery of mobility , so that a return to the usual lifestyle and level of activity is possible. It slows down the wear and tear of the articular cartilage with the aim of being able to do without a partial or complete replacement of the knee joint ( knee prosthesis ) or to be able to delay it.

background

The AMIC process was first proposed by Behrens in 2003. It aims to expand surgical microfracturing to include larger cartilage defects over 2.5 cm².

AMIC is based on microfracturing; here the self-healing potential of the body is harnessed. In this case, contact the blood and bone marrow of tiny holes in the subchondral (cartilage-bearing) bone plate and fill the damaged cartilage area with a blood clot , the "super clot" so referred to. This blood clot contains all of the building blocks (e.g., progenitor cells , mesenchymal stem cells (MSC), cytokines, and growth factors ) that are needed to form new cartilage repair tissue in response to the injury. By applying a collagen membrane to the developing superthrombus, it is fixed and stabilized overall. It also improves the filling of the primary defect, which is an important parameter for a good result. In addition, the application of a collagen scaffold creates a protected environment in which cells can establish themselves, multiply and form repair tissue. The collagen membrane originally propagated for AMIC (sold under the brand name 'Chondro-Gide') is made up of two layers known as "bilayer structures", a dense, compact layer and a porous layer. Its clinical efficacy in autologous chondrocyte implantation , another method for repairing cartilage lesions, has been extensively studied.

The AMIC operation method is currently the treatment of cartilage damage in the knee , the ankle on the anklebone ( talus ) and in the hip applied.

Procedure

The surgery required for Autologous Matrix Induced Chondrogenesis (AMIC) is performed in a single pass. After an arthroscopic investigation of the cartilage damage and the decision for the AMIC procedure, a mini-arthrotomy is performed. First, the damaged cartilage is exposed and cleaned, carefully removing all unstable, degenerated cartilage parts, including the calcified cartilage layer. Then an impression of the lesion is made with a sterile, malleable material (e.g. aluminum foil) and transferred to the collagen membrane, which is then cut to the correct shape.

With a special awl, the surgeon then drills tiny holes / fractures in the subchondral bone plate ("microfracturing"). This allows blood and bone marrow to leak out and form a blood clot that contains the building blocks necessary for cartilage formation.

The collagen membrane, cut to size, is applied to the microfracture area either with fibrin glue (of autologous origin or as a commercial product) or with a suture. The stable positioning of the membrane is verified by flexing the joint and the wound is then closed.

A critical phase and basically an indispensable requirement for the success of the AMIC procedure is the subsequent rehabilitation program , which must be strictly adhered to. There are guidelines and recommendations for this, but these must be adapted to the needs of the respective patient.

Clinical results

A number of general factors are known to affect the clinical outcome after cartilage repair, regardless of the method used. This includes the sex and age of the person affected, the size and exact location of the articular cartilage defect, the surgical technique used and the protocol for postoperative rehabilitation. The latter has proven to be particularly important for microfracturing and thus also for AMIC.

Surgical microfracture was developed by Steadman in the late 1980s and early 1990s . It is a well-documented cartilage repair technique and an initial treatment option for small cartilage lesions. AMIC was developed with the aim of remedying certain disadvantages of surgical microfracture, e.g. B. the variable volume of newly formed cartilage tissue and the functional deterioration over time. In addition, the intention was to develop a simple technique by which the developing, sensitive blood clot could be fixed in larger defects and possibly to improve the chondrogenesis (cartilage formation) of the mesenchymal stem cells.

The first in-vitro work in which the ability of a collagen membrane to attach cartilage-forming cells (e.g. MSC) from bone marrow was described was published in 2006 by Kramer et al. published. After the subchondral bone had been perforated (microfracturing), the collagen membrane was applied to the superthrombus that was forming. MSC were then taken from a tiny excess of bone marrow-permeated membrane. It could be shown that these had successfully differentiated into adipogenic, osteogenic (fat and bone forming) and - most importantly - chondrogenic lines. Chondrogenesis is the process of cartilage formation from condensing mesenchymal tissue that differentiates into chondrocytes and then begins to secrete the molecules that make up the extracellular matrix (i.e., cartilage repair tissue).

In another in vitro study, Dickhut et al. asked whether a combination of collagen membrane (Chondro-Gide) and fibrin glue would support in vitro chondrogenesis of MSC and allow a local release of the bioactive transforming growth factor β1 (TGF-β1) . The researchers were able to show that the combination enabled high biofunctionality with improved chondrogenesis and local long-term supply with TGF-β1. TGF-β1 is a protein secreted by the body that is involved in numerous cell functions, such as: B. in the regulation of cell growth as well as in the proliferation and differentiation as well as the "programmed" death of cells ( apoptosis ). In addition, Dickhut et al. show that the dimensional stability of the repair tissue that formed was improved compared to constructs free of collagen membrane.

The application of a collagen scaffold to microfractured cartilage lesions has also been described in a study published by Gille et al. conducted study on sheep. It was possible to show that the thickness of the repair tissue when using a scaffold, in particular a collagen I / III membrane, was greater compared to microfracturing alone. The authors concluded from this that the formation of repair tissue was stimulated. The same author also reported the first clinical results with the AMIC technique in 2010. A total of 27 patients who underwent AMIC surgery between 2003 and 2005 were included in this prospective study . The follow-up period was 24 to 62 months, with a mean of 37 months. The mean age of the patients was 39 years (age range: 16 to 50 years). The mean defect size was 4.2 cm² (size range: 1.3–8.8 cm²). Three patients had to leave the study. 20 of the 23 patients questioned answered that they were very satisfied with the results of the operation and said that overall knee function had improved. The result scores used (Lysholm, ICRS, Meyer, Tegner, Cincinnati) showed a significant increase over 24 months, with a slight decrease from the third year after the operation. Patients with lesions larger than 8 cm² had significantly reduced scores. Gille et al. concluded that the treatment of chondral knee lesions with the AMIC technique is effective and safe with the appropriate case selection.

Another clinical description of the AMIC technique and its early results can be found in the work of Benthien, de Girolamo, Wiewiorski, and Valderrabano.

With one exception, the clinical results are limited to case series and other non-comparative studies. The by Anders et al. Randomized controlled trial (RCT) published in 2013 aims to assess the efficacy and safety of AMIC versus microfracture. In the result scores used (modified ICRS, modified Cincinnati, VAS pain), no significant differences between the two treatment methods can be identified. The radiological evaluation shows slightly poorer results for AMIC, especially with regard to the surface of the regenerated tissue and the degree of integration. Due to the low number of cases, weaknesses in study planning and implementation as well as short observation periods, the study is limited in its informative value.

The 5-year follow-up of the same study was published by Volz in 2018 and shows significantly better results in terms of knee function for the two AMIC groups compared to the microfracture group. With regard to the pain scores, AMIC - albeit not statistically significant - achieved better results. The long-term studies by Schiavone-Panni (7 years follow-up) and de Girolamo (9 years follow-up) confirm that the AMIC technique can achieve a permanent improvement in knee function and a reduction in knee pain in focal cartilage / bone lesions . The AG Tissue Regeneration - a working group of the German Society for Orthopedics and Traumatology recommends the AMIC procedure in the knee for cartilage lesions around 2.5 cm² in the ankle for cartilage / bone lesions from 1.5 cm² and in the hip for cartilage lesions smaller than 1.5 cm² 2 cm².

Further developments

As a promising further development to the two-dimensional membranes, a new type of chitosan- based gel-like biomatrix (BST-CarGel) received approval as a medical product in accordance with Directive 93/42 / EEC in April 2012 .

The biomatrix is ​​first mixed with autologous blood and then applied to the cleaned, microfractured cartilage defect. It stabilizes and protects the blood clot, is biodegradable and supports the natural wound healing process. It can be introduced arthroscopically.

In an international, randomized clinical study, Stanish et al. the effectiveness and safety of the biomatrix compared to microfracturing. The results of the phase III clinical study were presented at the 10th World Congress of the International Cartilage Repair Society (ICRS) from May 12th to 15th, 2012 in Montreal , Québec , Canada . The study shows that both the filling ridge and the quality of the new tissue were statistically significantly better after treatment with the gel-like biomatrix than after microfracture, with a comparable safety profile.

See also

literature

Reference books

Review article (Reviews)

Web links

Individual evidence

  1. ^ German Patent and Trademark Office (DPMA), register number 30255356 . November 11, 2002. Retrieved January 25, 2013.
  2. ↑ World Intellectual Property Organization (WIPO), register number 840373 . August 18, 2004. Retrieved January 25, 2013.
  3. ↑ P. Behrens: Matrix-coupled microfracturing . In: Arthroscopy . 18, No. 3, 2005, pp. 193-197. doi : 10.1007 / s00142-005-0316-0 .
  4. ↑ AH Gomoll, C Probst, J Farr, BJ Cole, T Minas: Use of a type I / III bilayer collagen membrane decreases reoperation rates for symptomatic hypertrophy after autologous chondrocyte implantation . In: Am J Sports Med . 37 Suppl 1, November 2009, ISSN  0363-5465 , pp. 20S-23S. doi : 10.1177 / 0363546509348477 . PMID 19841142 .
  5. ↑ M Steinwachs, PC Kreuz: Autologous chondrocyte implantation in chondral defects of the knee with a type I / III collagen membrane: A prospective study with a 3-year follow-up . In: Arthroscopy . 23, No. 4, April 2007, ISSN  1526-3231 , pp. 381-387. doi : 10.1016 / j.arthro.2006.12.003 . PMID 17418330 .
  6. ↑ CR Gooding, W Bartlett, G Bentley, JA Skinner, R Carrington, A Flanagan: A prospective, randomized study comparing two techniques of autologous chondrocyte implantation for osteochondral defects in the knee: Periosteum covered versus type I / III collagen covered . In: Knee . 13, No. 3, June 2006, ISSN  0968-0160 , pp. 203-210. doi : 10.1016 / j.knee.2006.02.011 . PMID 16644224 .
  7. ↑ JW Alford, BJ Cole: Cartilage restoration, part 2: techniques, outcomes, and future directions . In: Am J Sports Med . 33, No. 3, March 2005, ISSN  0363-5465 , pp. 443-460. PMID 15716263 .
  8. ↑ MR Steinwachs, T Guggi, PC Kreuz: Marrow stimulation techniques . In: Injury . 39 Suppl 1, April 2008, ISSN  0020-1383 , pp. S26-31. doi : 10.1016 / j.injury.2008.01.042 . PMID 18313469 .
  9. ↑ JM Hurst, JR Steadman, L O'Brien, WG Rodkey, KK Briggs: Rehabilitation following microfracture for chondral injury in the knee . In: Clin Sports Med . 29, No. 2, April 2010, ISSN  1556-228X , pp. 257-265, viii. doi : 10.1016 / j.csm.2009.12.009 . PMID 20226318 .
  10. ↑ JR Steadman, WG Rodkey, SB Singleton, KK Briggs: Microfracture technique for full-thickness chondral defects: Technique and clinical results . In: Oper Tech Orthop . 7, No. 4, October 1997, pp. 300-304. doi : 10.1016 / S1048-6666 (97) 80033-X .
  11. ↑ JR Steadman, WG Rodkey, JJ Rodrigo: Microfracture: surgical technique and rehabilitation to treat chondral defects . In: Clin Orthop Relat Res . No. 391 Suppl, October 2001, ISSN  0009-921X , p. S362-9. PMID 11603719 .
  12. ↑ JR Steadman, KK Briggs JJ Rodrigo, MS Kocher, TJ Gill, WG Rodkey: Outcomes of microfracture for traumatic chondral defects of the knee: average 11-year follow-up . In: Arthroscopy . 19, No. 5, ISSN  1526-3231 , pp. 477-484. doi : 10.1053 / jars.2003.50112 . PMID 12724676 .
  13. ↑ K Mithoefer, T McAdams, RJ Williams, PC Kreuz, BR Mandelbaum: Clinical efficacy of the microfracture technique for articular cartilage repair in the knee: an evidence-based systematic analysis . In: Am J Sports Med . 37, No. 10, October 2009, ISSN  1552-3365 , pp. 2053-2063. doi : 10.1177 / 0363546508328414 . PMID 19251676 .
  14. ^ J Kramer, F Böhrnsen, U Lindner, P Behrens, P Schlenke, J Rohwedel: In vivo matrix-guided human mesenchymal stem cells . In: Cell Mol Life Sci . 63, No. 5, March 2006, ISSN  1420-682X , pp. 616-626. doi : 10.1007 / s00018-005-5527-z . PMID 16482398 .
  15. ^ A Dickhut, V Dexheimer, K Martin, R Lauinger, C Heisel, W Richter: Chondrogenesis of human mesenchymal stem cells by local TGF-beta delivery in a biphasic resorbable carrier . In: Tissue Eng Part A . 16, No. 2, February 2010, ISSN  1937-335X , pp. 453-464. doi : 10.1089 / ten.TEA.2009.0168 . PMID 19705961 .
  16. ↑ J Gille, J Kunow, L Boisch, P Behrens, I Bos, C Hoffmann, W Köller, M Russlies, B Short: Cell-Laden and Cell-Free Matrix-Induced Chondrogenesis versus Microfracture for the Treatment of Articular Cartilage Defects: A. Histological and Biomechanical Study in Sheep . In: Cartilage . 1, No. 1, January 2010, pp. 29-42. doi : 10.1177 / 1947603509358721 .
  17. ↑ J Gille, E Schuseil, J Wimmer, J Gellissen, AP Schulz, P Behrens: Mid-term results of Autologous Matrix-Induced Chondrogenesis for treatment of focal cartilage defects in the knee . In: Knee Surgery, Sports Traumatology, Arthroscopy . 18, No. 11, November 2010, ISSN  1433-7347 , pp. 1456-1464. doi : 10.1007 / s00167-010-1042-3 . PMID 20127072 .
  18. ↑ L de Girolamo, G Bertolini, M Cervellin, G Sozzi, P Volpi: Treatment of chondral defects of the knee with one step matrix-assisted technique enhanced by autologous concentrated bone marrow: in vitro characterization of mesenchymal stem cells from iliac crest and subchondral bone . In: Injury . 41, No. 11, October 2010, ISSN  1879-0267 , pp. 1172-1177. doi : 10.1016 / j.injury.2010.09.027 . PMID 20934693 .
  19. ↑ JP Benthien, P Behrens: Autologous matrix-induced chondrogenesis (AMIC). A one-step procedure for retropatellar articular resurfacing . In: Acta Orthop Belg . 76, No. 1, April 2010, ISSN  0001-6462 , pp. 260-263. PMID 20503954 .
  20. ↑ JP Benthien, P Behrens: Autologous Matrix-Induced Chondrogenesis (AMIC): Combining Microfracturing and a Collagen I / III Matrix for Articular Cartilage Resurfacing . In: Cartilage . 1, No. 1, January 2010, pp. 65-68. doi : 10.1177 / 1947603509360044 .
  21. ^ M Wiewiorski, A Leumann, O Buettner, G Pagenstert, M Horisberger, V Valderrabano: Autologous matrix-induced chondrogenesis aided reconstruction of a large focal osteochondral lesion of the talus . In: Arch Orthop Trauma Surg. . January 2010, ISSN  1434-3916 . doi : 10.1007 / s00402-010-1048-9 . PMID 20091174 .
  22. ^ V Valderrabano, M Miska, A Leumann, M Wiewiorski: Reconstruction of osteochondral lesions of the talus with autologous spongiosa grafts and autologous matrix-induced chondrogenesis . In: Am J Sports Med. . 41, No. 3, March 2013, pp. 519-527. doi : 10.1177 / 0363546513476671 . PMID 23393079 .
  23. ↑ S Anders, M Volz, H Frick, J Gellissen: A Randomized, Controlled Trial Comparing Autologous Matrix-Induced Chondrogenesis (AMIC®) to Microfracture: Analysis of 1- and 2-Year Follow-Up Data of 2 Centers . In: Open Orthop J. . May 7, 2013, ISSN  1874-3250 , pp. 133-143. doi : 10.2174 / 1874325001307010133 . PMID 23730377 .
  24. ↑ VOLZ, M., et al .: A randomized controlled trial demonstrating sustained benefit of Autologous Matrix Induced Chondrogenesis over microfracture at five years. Ed .: Int Orthop. No. 41 (4) , April 2017, p. 797-804 .
  25. ↑ SCHIAVONE-PANNI, A., et al .: Good clinical results with autologous matrix-induced chondrogenesis (AMIC) technique in large knee chondral defects . Ed .: Knee Surg Sports Traumatol Arthrosc. No. 26 (4) , April 2018, p. 1130-1136 .
  26. ↑ DE GIROLAMO, L., et al .: Autologous Matrix-Induced Chondrogenesis (AMIC) and AMIC Enhanced by Autologous Concentrated Bone Marrow Aspirate (BMAC) Allow for Stable Clinical and Functional Improvements at up to 9 Years Follow-Up: Results from a Randomized Controlled Study . Ed .: J. Clin. Med. No. 8 , 2019, pp. 392 .
  27. ↑ NIEMEYER, P., et al .: Significance of Matrix-augmented Bone Marrow Stimulation for Treatment of Cartilage Defects of the Knee. A consensus Statement of the DGOU Working Group on Tissue Regeneration . Ed .: Z Orthop Unfall. 2018.
  28. ↑ AURICH, M .: Treatment of osteochondral lesions in areas the Ankle: A Guideline from the Group "Clinical Tissue Regeneration" of the German Society of Orthopedics and Traumatology (DGOU) . Ed .: Z Orthop Unfall. 2016.
  29. ↑ FICKERT, S .: Biologic Reconstruction of Full Sized Cartilage Defects of the Hip: A Guideline from the DGOU Group “Clinical Tissue Regeneration” and the Hip Committee of the AGA . Ed .: Z. Orthop Unfall. 2017.
  30. ↑ Follow-Up Study Comparing BST-CarGel and Microfracture in Repair of Articular Cartilage Lesions in the Knee . Identifier: NCT01246895 ClinicalTrials.gov, study description (English)