Purpose: Articular resurfacing by treatment of chondral defects may include chondral abrasion, autologous chondrocyte Implantation (ACI), matrix-induced chondrocyte transplantation (MACT) or osteochondral autologous transplantation (OATS). This technical note describes the method of autologous matrix-induced chondrogenesis (AMIC), a one-step procedure combining subchondral microfracture with the fixation of a collagen I/III membrane with fibrin glue or sutures. Methods: This is a technical note on the AMIC procedure and its further development. Results and conclusion: This method is applied primarily in chondral or osteochondral lesions of the knee. Indications and contraindications are provided; the technique is described. The further development of AMIC is described with an increased focus on the subchondral zone and the complex of cartilage and bone, the osteochondral unit, which receives increased attention in cartilage research. Level of evidence: I

Behrens, Peter

Benthien, Jan

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KNEEThe treatment of chondral and osteochondral defects of the kneewith autologous matrix-induced chondrogenesis (AMIC):method description and recent developmentsJan Philipp Benthien • Peter BehrensReceived: 18 July 2010 / Accepted: 6 December 2010 / Published online: 14 January 2011 Springer-Verlag 2011AbstractPurpose Articular resurfacing by treatment of chondraldefects may include chondral abrasion, autologous chon-drocyte Implantation (ACI), matrix-induced chondrocytetransplantation (MACT) or osteochondral autologoustransplantation (OATS). This technical note describes themethod of autologous matrix-induced chondrogenesis(AMIC), a one-step procedure combining subchondralmicrofracture with the fixation of a collagen I/III mem-brane with fibrin glue or sutures.Methods This is a technical note on the AMIC procedureand its further development.Results and conclusion This method is applied primarilyin chondral or osteochondral lesions of the knee. Indica-tions and contraindications are provided; the technique isdescribed. The further development of AMIC is describedwith an increased focus on the subchondral zone and thecomplex of cartilage and bone, the osteochondral unit,which receives increased attention in cartilage research.Level of evidence IV.Keywords Chondral defects  Osteochondral defects AMIC  MicrofracturingIntroductionChondral or osteochondral defects are of particular interestfor the orthopaedic surgeon as these normally do notheal spontaneously. During the past 20 years regenerativetechniques applying collagen membranes on treated carti-lage defects were developed. It was demonstrated that thesecollagen II membranes facilitate differentiation of MSCsinto chondrocytes whilst providing a scaffold for thechondrocytes to form cartilage [14, 21]. Fixation of thescaffold with commercially available fibrin glue seems tobe advantageous as fibrin glue seems to act as an additionalscaffold for chondrocytes and that its contents in TGF b areconsiderable, possibly helping in differentiation of mes-enchymal stem cells [14].The cartilage resurfacing procedures most frequentlyapplied are as follows: abrasion arthroplasty anddebridement [7, 12], the autologous chondrocyte implan-tation (ACI) as introduced by Brittberg [8, 9, 16, 18], themethod of microfracturing as developed by Steadmann[22, 23] and the osteochondral autologous transplantationsystem (OATS) [6].The ACI involves a two-step proce-dure transplanting chondrocytes previously taken from adonor site into a cartilage defect [8, 9]. In microfractur-ing, the calcified subchondral bone/cartilage border isperforated, consecutively fibrous cartilage is developedfrom mesenchymal stem cells [22, 23]. OATS meanstaking autologous osteochondral grafts from a non-weightbearing joint site and transplanting them to the defect[2, 6, 11].The matrix associated chondrocyte transplantation(MACT) is a further development in cartilage resurfacingwhich allows previously harvested chondrocytes to differ-entiate into chondrocytes with the aid of a collagen scaffold[1, 3].J. P. Benthien (&)Department of Orthopaedic Surgery, University of Basel,Spitalstr. 21, 4031 Basel, Switzerlande-mail: jbenthien@uhbs.chP. BehrensDepartment of Orthopaedic Surgery, University of Luebeck,Luebeck, Germany123Knee Surg Sports Traumatol Arthrosc (2011) 19:1316–1319DOI 10.1007/s00167-010-1356-1The autologous matrix-induced chondrogenesis (AMIC)as first introduced by Behrens et al. [4, 13] further developsthe matrix/scaffold technique in combination with micro-fracturing. It is a less-expensive one-step procedure whichcombines microfracturing of the cartilage/bone-laminaafter debridement of the cartilage lesion with fixation of acommercially available porcine collagen I/III matrix. Thismatrix covers the blood clot and its mesenchymal stemcells (MSCs) whilst permitting the MSCs to develop intochondrocytes [4, 13, 14, 19].The objective of this technical note is to demonstrate theAMIC technique in its original form and its furtherdevelopment and to compare its results with the literature.Technical noteIndications for AMIC are symptomatic full thickness(ICRS grade 4) lesions and osteochondral lesions such as inosteochondrosis dissecans. The lesion should not exceed1.5 cm2, and the location should normally be in the weightbearing region, bearing the highest risk for degenerativejoint disease. Contraindications are kissing or multiplelesions, inflammatory diseases such as rheumatoid arthritis,tumour, an uncorrected ligamentous balancing or lesions ofthe cruciate and collateral ligaments, extension deficit ofmore than 10, flexion deficits of more than 100, mala-lignment and associated fractures. If an osteochondraldefect is present, the author’s preferred method is theclosure of the osseous defect with an autologous bonetransplant from the tibial head which may be harvestedduring the same procedure. The cancellous bone isimpacted into the defect, and the membrane is attached onthe defect with either fibrin glue or sutures.The procedure starts with an arthroscopy of the affectedjoint to verify the size and location of the defect and alsothe amount of accompanying disorder. After determiningthe size and location and after a diagnostic arthroscopyruling out accompanying lesions or ligamentous problems,an AMIC procedure may be initiated. A minimally invasivearthrotomy is performed and the defect is visualizedopenly. The defective cartilage tissue and subchondralbone is removed with a curette (Fig. 1a).If an osteochondral lesion is present, cancellous bonemay be harvested from the tibial head using the sameincision. An aluminium template may be used to determinethe size of the lesion and the appropriate membrane(Fig. 1b).Membrane and template should be slightly undersized toavoid dislocation after movement. Microfracturing used tobe performed in the original method described by Behrenset al. [4, 13] with the corresponding microfracturing awls.We have further developed the perforation of thesubchondral zone according to the latest literature studieswhich seem to demonstrate that the subchondral stroma isbetter reached by drilling [10, 16]. A 1.1 mm K-wire isnow drilled either by hand or by machine with constantcooling being applied so the subchondral bone is reached(Figs. 2, 3a).A partially autologous fibrin glue may be manufacturedby centrifuging a blood sample from the patient and mixingthe yielded thrombin with allogenic fibrinogen from com-mercially available fibrin glue. Commercially availableallogenic fibrin glue or suturing for fixation may also beapplied (Fig. 3b).Suturing, however, may lead to cartilage damage [3].Knecht et al. [17] have confirmed that glueing with fibrinFig. 1 Curettage of the defect and measuring of an aluminiumtemplateFig. 2 Microfracturing should be performed with a 1.1 mm K-wirewhich is the author’s preferred method of treatment. Cooling withsterile NaCl solution is advisable. Drilling seems to reach thesubchondral bone better than microfracturing aloneKnee Surg Sports Traumatol Arthrosc (2011) 19:1316–1319 1317123glue leads to sufficient stability of a collagen membrane. Itis important that the collagen membrane is placed slightlybelow the cartilage level because displacement aftermoving the joint is almost certain if the membrane staysabove the cartilage rim. (Fig. 3c).The joint should be gently moved intra-operatively.Inspection of the site is advisable and should confirm thatthe membrane remains in place.The postoperative management is as follows: maximumweight bearing 15–20 kg for 6 weeks, common thromboseprophylaxis with a low molecular heparin, and continuousjoint movement. Removal of a possible drain 24 h aftersurgery is recommended. Care should be exercised that thesuction is removed as this could lead to membranedislocation.Maximum flexion of the knee should not exceed 30 for2 weeks following the operation. Flexion is raised to 60and 90 for another 2 weeks, respectively. The patient isseen in the outpatient clinic 6 weeks after the appointment.DiscussionThe most important feature of the present technical note isthe introduction of a combined microfracturing and colla-gen method for cartilage surgery which is further developedaccording to the latest findings in cartilage physiology.Chondral or osteochondral injuries affect a broad spec-trum of patients with knee pain. They may be eitherposttraumatic or with an unknown cause such as osteo-chondrosis dissecans. Young active adults may beinvolved. These defects may eventually lead to progressivejoint destruction by osteoarthritis, thus gaining significantinterest by the orthopaedic surgeon to develop propertreatment. However, as many studies treat this subject, noprocedure may be recommended as the treatment of choiceat this time [5].Gille et al. [13] reported good mid-term results of AMICreporting that 87% of the treated patients were highlysatisfied with the result. This compares well with the resultsafter microfracturing alone [20, 22, 23].Drilling does not seem to have such a deleterious effecton the subchondral bone matrix as was once expected butinstead leads to better access to the bone-marrow stroma inthe rabbit model [10]. A study of de Girolamo et al. [15]suggests a difference in mesenchymal stem cells (MSCs)harvested after microfracturing and primarily from the iliaccrest. It is suggested that the MSCs from the microfracturedareas demonstrate a different and comparatively irregularpattern than those harvested from the iliac crest.Following these new findings in cartilage surgeryresearch, the authors have, therefore, modified the originalAMIC method and switched from conventional micro-fracturing awls to drilling with K wires. It seems to becomeincreasingly important to include the osteochondral unitinto cartilage surgery rather than focus on the cartilagealone as this is likely a complex system including inter-action between bone and cartilage [16].The AMIC procedure was developed as a one-stepprocedure that may be cost-effective and qualify forreimbursement by the health insurances. It has the advan-tage of a one-step procedure that combines microfracturingwith chondrocyte differentiation from MSCs on a collagenmatrix. The initially formed blood clot as produced bymicrofracturing is protected by the collagen membrane.However, since this is a new method, it has yet to show itsadvantages over microfracturing or simple de´bridementalone. A disadvantage which may be minimized by mini-mally invasive methods is the open procedure. Prospectiverandomized studies should be implemented investigatingthis method, especially in comparison with microfracturingalone.The AMIC procedure may be a cost-effective option forthe surgeon treating cartilage defects. It is easy to apply,and it supplies the cartilage surgeon with a procedure tooffer a patient with a symptomatic cartilage defect.ConclusionCombining micro-fracturing with a collagen I/III scaffoldmay be a cost-effective option for articular resurfacing byFig. 3 a–c After microfracturing of the defect, fibrin glue is applied and the collagen II membrane attached. From Gille et al.: Mid-term resultsof autologous matrix-induced chondrogenesis for treatment of focal cartilage effects in the knee, Knee Surg Sports Traumatol Arthrosc 20101318 Knee Surg Sports Traumatol Arthrosc (2011) 19:1316–1319123treating chondral or osteochondral defects. More prospec-tive randomized Level of Evidence 1 and 2 studies shouldcompare the results of the AMIC procedure as compared tomicro-fracturing alone and MACI, both related to AMICbut more cost intensive. Drilling the subchondral zone andreaching the bone-marrow stroma may be more effectivethan microfracturing with an awl alone.References1. Bartlett W, Skinner JA, Gooding CR, Carrington RWJ, FlanaganAM, Briggs TWR, Bentley G (2005) Autologous chondrocyteimplantation versus matrix-induced autologous chondrocyteimplantation for osteochondral defects of the knee. A prospectiverandomized study. J Bone Joint Surg Br 87:640–6452. Behrens P, Bosch U, Bruns J et al (2004) Indications andimplementation of recommendation of the working group ‘‘Tis-sue regeneration and Tissue Substitution’’ for autologous chon-drocyte transplantation. Z Orthop Ihre Grenzgeb 142:529–5393. Behrens P, Bitter T, Kurz B et al (2006) Matrix associatedautologous chondrocyte transplantation: a 5 year follow up. 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The treatment of chondral and osteochondral defects of the knee with autologous matrix-induced chondrogenesis (AMIC): method description and recent developments

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The treatment of chondral and osteochondral defects of the knee with autologous matrix-induced chondrogenesis (AMIC): method description and recent developments

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