Matrix-Induced Autologous Chondrocyte Implantation

1 MACIM atrix- induced Autologous Chondrocyte ImplantationDAMAGE to the hyaline articular cartilage in the knee may lead to the accelerated onset of osteoarthritis. Lesions ofthe articular cartilage affect millions of people worldwide, but treatment is hampered by the fact that in adult lifehyaline articular cartilage is limited in its ability to regenerate. This article briefly outlines the structure and functionof hyaline articular cartilage, previous surgical treatment for articular cartilage defects and an innovative newtreatment known as Matrix-Induced Autologous Chondrocyte Implantation (MACI).As MACI is not appropriate for allcandidates with cartilage damage, this information sheet also includes guidelines on patient selection and highlightsthe necessity for appropriate pre and post surgery Information SheetStage 1: BiopsyWhat is Hyaline ArticularCartilage and what function doesit serve?

2 Hyaline articular cartilage covers the ends ofthe bones in movable joints. Healthy hyalinearticular cartilage has a pale and glisteningappearance, and a firm and smooth texture. Itserves as a load-bearing elastic material that isresponsible for the frictionless movement ofthe surfaces of joints. It is capable ofwithstanding loads up to seven times theweight of the happens if the HyalineArticular Cartilage layer isdamaged?Despite its durability, hyaline cartilage does nothave a blood supply and consequently has alimited capacity for regeneration. Oncedamaged the human body forms fibrocartilageto take its place but this surrogate tissue is verysoft and does not possess the appropriatestructural properties needed to dissipate theforces stimulated by the body during day to daylife. patients with significant cartilage defectsfrequently have persistent joint pain, swelling,and "catching" in the knee.

3 Full thicknesscartilage defects will never heal of their ownaccord and ultimately lead to have cartilage defects beentreated prior to the developmentof MACI?Previously, a wide variety of surgical proceduressuch as knee debridement and abrasionarthroplasty, designed to promote fibrousrepair of cartilage defects have been tried andfound wanting. In young patients cartilagedefects cannot be treated by joint replacementbecause of the risks of early loosening andpremature wearing of the is MACI & how does it work?MACI is an innovative new method ofautologous Chondrocyte Implantation (ACI)for treating defects in the articular cartilageand for filling them with regenerative tissue. Itoffers an effective treatment by isolating andgrowing the patient s own cartilage buildingblocks, known as chondrocytes, and re-implanting these cells into the damaged areawithin the knee joint via surgery using aspecialised collagen does MACI involve?

4 The procedure is performed in two as a day patient, a sample of cartilagecells is removed arthroscopically from thenon-weight bearing part of the knee. Thechondrocyte cells are then isolated and grownin a special laboratory using highly developedtissue engineering procedures that takeapproximately four weeks. The second stageinvolves implanting the Chondrocyte cells thathave been seeded onto the collagenmembrane into the defect in the knee viaspecialised knee surgery. A post-operativehospital stay of approximately 2 - 4 days willgenerally be required following surgery. Afterwhich the patient is discharged wearing aprotective knee brace and using two can I best prepare forsurgery and my postoperativerecovery?The rehabilitation process for MACI shouldbegin prior to surgery, as patients need to bephysically and mentally prepared for theiroperative procedure and the lengthyrehabilitation process.

5 Patient education isessential, as the integrity of the chondrocyterepair must be does recovery from MACI involve?Following surgery it is necessary to undergo arehabilitation program so as to stimulate theimplanted chondrocytes to adapt to theirnatural function. patients are required toprotect the repair from weight bearing stressesand are restricted to toe-touch ambulationwith two crutches for the first sixpostoperative weeks. Immediately aftersurgery the amount of knee bend (flexion) isrestricted and a brace must be worn to ensurethe protection of the cartilage repair. As arough guide, patients should achieve between60-90 knee flexion by three-weeks, 90-120 knee flexion by six weeks and have returned toa normal range (approx 130-160 ) by 12 weekspost surgery. At the 12-week time-pointcompressive and decompressive forces,provided by full weight bearing, furtherstimulate the chondrocytes to synthesise thecorrect matrix molecules.

6 However, return towork and sport and recreational activitiesshould be carefully controlled and graduallyprogressed. Although the cartilage defect maywell have been filled with hyaline-like cartilagewithin the first few months, it is not advisableto undertake stressful extension or weightbearing activities, such as squats or runningbefore twelve months. Maturation andhardening of the new-formed cartilage will notbe complete until 11-24 months have was this techniquedeveloped and how successful hasit been? Autologous Chondrocyte Implantation (ACI),in combination with periosteal grafts, havebeen employed to treat cartilage defectssince 1987 with successful results. Since thenover five thousand people worldwide havebeen treated using this technique. Thepatented Matrix-Induced ACI technique (by Stage 3: MACI - fully healedPatient Information SheetStage 2: Implantation - membrane in positionGenzyme) is a modification of the periostealACI technique and addressed the problems ofusing a periosteum patch by replacing it withan inert porcine collagen membrane.

7 The typeI/III collagen employed is biocompatible andhas been used in plastic surgery for manythousands of this technique, the cells are actually seededdirectly onto the collagen type I/IIIbiomembrane to form a biocomposite. Cellsadhering to the inert membrane aremechanically stable at the time ofimplantation so there is no longer the risk ofleakage. The MACI technique is moreconvenient as the pre-cut patch is now gluedin position with fibrin glue that only takes oneminute to set, compared to the hour requiredto suture a patch of collagen or MACI technique can also be performedvia mini arthrotomy due to the fact thatsutures are no longer needed. This has theadded benefit of reducing soft tissue damageto the affected this treatment suitable for me?The guidelines for selection of patients suitablefor this procedure are as follows: Cause of defect if this has been causedby trauma or osteochondritis dessicansthe patient is suitable.

8 If it is associatedwith rheumatoid or inflammatoryarthritis, cartilage regeneration in this wayis not suitable. The age limits are 15 to 55 years of age. If the knee is unstable or malaligned in anyway then ACI is only indicated once theinstability or malalignment has beenaddressed. However these problems may beaddressed at the time of cartilageimplantation. ACI should not be used in the presence ofthe following situations: obesity greater thanone and a half times the ideal body weightfor height, excessive bow leg or knock kneedeformities. The patient must be able and willing tocooperate with a clearly defined andcontrolled rehabilitation I have severe osteoarthritis and have been scheduled for aknee replacement, is MACI suitable for me?No. It is likely that if you scheduled for a kneereplacement that the arthritis in your kneehas gone too far to be addressed by this procedure is performedsuccessfully, will it prevent kneereplacement?

9 In all likelihood this procedure may reduceyour chance of knee replacement but as this isa relatively new technique, we require morelong-term information to answer this this technique suitable fortreating rheumatoid arthritis?No. Progressive inflammatory or rheumatoidarthritis would simply continue to erode thearea of enhanced isn t MACI recommended forpeople over the age of 55?The Chondrocyte cells of older patients do notgrow as those from young patients . In additionthe articular cartilage within the knees ofpatients over 55 years is usually too damagedfor the procedure to be beneficial. Howeverplease consult your surgeon for definitiveanswer to this this technique suitable toreplace torn cartilage?There are two types of cartilage in the knee,firstly the joint lining and secondly the menisci,which act as shock absorbers between the twojoint surfaces. It is the joint lining that issuitable for ACI.

10 The so called "torn cartilage"or meniscus is not suitable for this kind oftechnique although work is currently beingconducted on transplant menisci and thistechnology may be available in years to MACI suitable to treat cartilagedefects in other joints in the body?Whilst currently MACI is restricted totreatments of defects within the knee, ankleand shoulder joint, the use of MACI for localcartilage defects in other joints is currentlyunder could I commence drivingfollowing MACI?Approval needs to be obtained from theoperating surgeon; however, it has been ourexperience that patients usually are givenclearance to recommence driving approximately4 to 6 weeks following could I return to workfollowing MACI?Upon clearance from the operating surgeon,but also depends on the demands of the example, it has been our experience thatpatients can return to desk jobs after 3 is the length of hospital stayfollowing MACI?