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AUTOLOGUS CHONDROCYTE IMPLANTATION PRIYANK
The document summarizes a journal club discussion on autologous chondrocyte implantation (ACI) for treating articular cartilage defects in the knee. It provides details on the ACI procedure, which involves harvesting cartilage cells from a patient's knee, growing them in culture, and implanting them back into the defect using a periosteal patch or collagen membrane. The document compares ACI to other cartilage repair techniques like microfracture and drilling, finding ACI can regenerate hyaline-like cartilage while other techniques only produce fibrocartilage with limited lifespan. Rehabilitation guidelines and long-term assessment of ACI grafts via MRI, biopsy and arthroscopy are also summarized.
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Introduction to journal club presentation on Autologous Chondrocyte Implantation (ACI) and speakers.
This section discusses ACI's effectiveness in treating knee joint cartilage defects, including statistics on lesion types and surgical outcomes.
Description of a multicentric trial involving 28 patients and evaluations of clinical outcomes and MRI results after ACI.
Details about articular cartilage structure, function, common chondral injuries, and their prevalence among patient populations.
The symptomatic nature of full-thickness articular defects and the limitations of traditional treatment options leading to ACI.
Background and key historical advancements leading to ACI, including early applications of cell engineering in orthopedics.
Criteria for identifying suitable patients for ACI, detailing age, disability, joint condition, and other required factors.
Strengths, limitations, and methodologies associated with different ACI techniques including MACI and standard ACI practices.
Detailed explanation of the CARTICEL procedure, including patient preparation, cartilage biopsy, and implantation phases.
Guidelines for rehabilitation post-ACI surgery, emphasizing weight-bearing activities and gradual recovery milestones.
Comparison of ACI with other cartilage treatment methods, evaluating advantages and disadvantages of each methodology.
Results from ACI procedures showcasing clinical improvement rates and considerations for further research on ACI vs. MACI.
Recent advancements in cartilage repair technologies, including biomaterials and their potential for enhancing ACI outcomes.
Closing remarks and acknowledgment following the comprehensive discussion on Autologous Chondrocyte Implantation.
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AUTOLOGUS CHONDROCYTE IMPLANTATION PRIYANK
- 1. journal club (22-10-09)topic: autologuschondrocyte implantation
- 2. topic : autologuschondrocyteimplantationMODERATOR :DR M.BANSAL (M.S. ,D.N.B.)
- 3. DR. P .GUPTA(M.S.) SPEAKER : PRIYANK GUPTA
- 4. THE ROLE OFAUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TREATMENT OF ARTICULAR CARTILAGE DEFECTS IN THE KNEE JOINT J. A. L. Hart; and J. PaddlePURPOSE: To define the role of ACI in treatment of cartilagedefects in the knee joint.METHOD: 106 articular cartilage defects in 79 knees of 77 patientswere treated by ACI as described by Brittberg et al, 1994. -43.5%of the lesions involved the patella, -35.2% the femoral condyles,-16.7% the trochlea, and -4.6% the tibial condyles. -20% of kneeshad more than one defect. Associated biomechanical procedureswere carried out in 88.7%.
- 5. RESULTS:ASSESSEDARTHROSCOPICALLY 9 MONTHSAFTER IMPLANTATION70 lesions in 58 knees and 56 patients
- 6. 4 eligible patientswerenot assessed.
- 7. The average ICRSrepair score (maximum 12)was as follows:-Tibialcondyle 11.5 (4 defects); -Patella 11.3(32 defects); -Femoral condyle 11.0(23 defects) -Trochlea10.7 (11 defects). Synovitis was markedly reduced in all kneeswith well healed defects.
- 8. Contraindications to ACIin this serieswere:-Non-contained defects-Bi-polar lesions,-Patients greaterthan 45 years,-Uncorrected biomechanics,-Regional pain syndrometype 1,-Limited joint movement,-Defective subchondral boneplate.CONCLUSION:ACI EFFECTIVELY REPAIRS ARTICULAR CARTILAGE DEFECTSIN THE KNEE JOINT, PROVIDED THAT THE CONTRAINDICATIONS ARE RECOGNISED.Unlike other series, the results for the patella, patellofemoraljoint have matched those for the femoral condyle. This is attributedto the simultaneous biomechanical correction of the patellofemoraljoint. Stabilisation of the articular surface results in resolutionof synovitis.
- 9. AUTOLOGOUS CHONDROCYTE GRAFTS:MULTICENTRIC TRIAL WITH 28 KNEE IMPLANTATIONS WITH MORE THAN TWO YEARS FOLLOW-UPJournal of Bone and Joint Surgery - British Volume, Vol 90-B, Issue SUPP_II, 252Purpose of the study: Spontaneous repair of lost deep chondraltissue is minimal in the knee joint. A clinical trial of chondrocyteautografts as described by Brittberg and Peterson was undertakenby the Nantes University Hospital and the French Society ofArthroscopy in 1999.
- 10. Material and methods:Twenty-eight patients, mean age 28 years,underwent surgery in eight centers. Etiologies were:osteochondritis(n=14), isolated posttraumatic chondorpathy (n=7), chondropathyand full-thickness ACL tear (n=7). All lesions involved thecondyles and were deep (ICRS grds 3 and 4). Mean surface areainvolved after debridement was 490 mm2 (range 150–1000mm2). Patients were followed three years after the autologousgrafting to assess functional outcome. An MRI was obtained at2–3 years. Thirteen control arthroscopy procedures wereperformed including eight with biopsy specimens for histologyand immunohisto-chemistry studies.
- 11. RESULTS: Twenty-six patientswere reviewed at > 2 yrs There were no general complications,
- 12. Three patientspresenteda partial avulsion of the graft treated by arthroscopy and oneunderwent arthrolysis at six months.
- 13. FUNCTION improvedin allpatients except three and pain improved in all.
- 14. THE ICRS SCOREimprovedfrom 43 points (range 19–70) to 77 points (range39–84).
- 15. Sixteen control MRIswere available and showedthat
- 16. the graftwas hypertrophic in eleven cases,
- 17. on level infour,and insufficient in one.
- 18. Marginal integration wasgoodin 11 cases and partial in five.
- 19. Subchondral integrationwascomplete in ten cases and mediocre in six.
- 20. THE ARTHROSCOPICSCORE wasnearly normal (score 8–11) in eight cases andabnormal in five (score 4–7).
- 21. THE HISTOLOGICAL CLASSaccordingto Knutsen (hyaline richness) was:
- 22. one in group1 (>60%),
- 23. three in group2 (> 40%),
- 24.
- 25. onein group4 (bony or fibrous tissue).
- 26. Function score (r=0.78andMRI score (r=0.76) were correlated with arthroscopic sores.There was no correlation with the histological results.DISCUSSION:CLINICAL OUTCOME WAS IMPROVED IN MORE THAN 80% OFCASES, SIMILAR TO RESULTS REPORTED FOR HISTOLOGICAL SERIES.The arthroscopic and histological results were equivalent tothose reported by Knutsen but inferior to those reported byBentley or Peterson.
- 27. Articular CartilageChondrocytes (cartilagecells) embedded in aHighly specialised E.C.M.
- 28.
- 29. Provides resistance totensile,compressive and shear forces
- 30. Acts as asmooth , efficient surface for motion. Hyaline Cartilage StructureThe “stuff” of cartilage:Functions of the Articular Cartilage :– Distribute load– Absorb shock
- 31. Chondral Injuries:Commonly these injuries heal by scar tissue formation :
- 32. Prevalence and Incidence993consecutive arthroscopies – 66% articular cartilage pathology, 11% full thickness, localised lesions suitable for repair proceduresAroen A, Loken S, Heir S, et al. Am J Sports Med 2004; 32: 211-1531000 arthroscopic procedures – 63% articular cartilage lesionsCurl WW, Krome J, Gordon ES, et al. Arthroscopy 1997; 13: 456-601000 consecutive arthroscopies – 19% localised chondral/osteochondral lesionsHjelle K et al. Arthroscopy 2002; 18: 730-4
- 33. Cartilage Injury Occursin Many FormsTraumasports or work relatedChronic instabilitylong term effects: ACL and othermeniscal deficiencyMal-aligned joint - deformityvarus / ValgusOsteochondritisDissecans [OCD]
- 34. Genetic pre-disposition /earlyarthritis
- 35. Articular Cartilage Defects:a treatment challenge• Most full-thickness defects are symptomatic– Pain, swelling, locking, catching, grinding• Left untreated,may progress to significant articular defectsMay lead to debilitatingosteoarthritis.
- 36. AND, WHAT ISIN OUR BASKET ????Arthroscopic Debridement :
- 37.
- 38.
- 39. MicrofractureMARROW STIMULATION TECHNIQUESAbrasion arthroplasty -to induce the growth of fibrocartilage into the chondral defect. (This fibrocartilage does not withstand shock or shearing force as well as the original hyaline cartilage, and may deteriorate over time.)
- 40. SO IT LEDUS TO SEARCH OF MORE PROMISING OPTION :AUTOLOGUS CHONDROCYTE IMPLANTATION
- 41. AutologousChondrocyte Implantation (ACI):BACKGROUNDJBJS [Am], 1987 Peterson et al, Gothenburg,– first application of cell engineering in orthopaedics
- 42. NEJM, 1994 Brittbergetal, Sweden,– successfuly regenerated hyaline-like cartilage in isolated chondral defects.Identifying a Carticel® PatientPatient Factors:Younger patients – < age 45 - 50 (avg. ~ 35 y.o.)Significant impairment:-Compromised daily livingactivities. -Refractory to treatmentObesity
- 43.
- 44. Willing & capableof rehabilitation program
- 45. Identifying a Carticel®Patient…….Joint Factors:Symptomatic cartilage defects -Moderate to large (> 2cm2 d.= 1.6) -On the distal femur (mfc / lfc /trochlea)-Average defect size > 4 cm2 -Either chondral or osteochondralRelatively healthy joint – -No arthritisCo-morbidities(meniscal tear, instability or malalignment) must be corrected prior or concurrent to implantation.Pre-requisite for surgery :Appropriate biomachenical alignment
- 46.
- 47. Range of motionNotrecommended for patients who have :an unstable knee
- 48. patients sensitive tomaterials of bovine origins
- 49. allergic to theantibiotic gentamicin
- 50.
- 51. yet in anyjoint other than the knee.AutologousChondrocyteImplantation (ACI)Strengths:
- 52. Can produce hyaline-likecartilage.
- 53. Can fill defectsregardless of size with functional repair tissue.
- 54. Moderate to largedefects that have failed previous intervention.
- 55. Repair tissue whichmatures , rather than deteriorates over time.
- 56.
- 57. Return to previouslevel of functioning“Biological Joint replacement”Limitations
- 58.
- 59.
- 60. Longer recovery ACI– Periosteum (cells under periosteum)ACI – Chondrogide (cells under membrane)MACI – Matrix Induced ACI (cells on membrane)Chondrogide Membrane
- 61.
- 62.
- 63. Resorbs in 3-4months ACIMACITechniques :
- 64. ACI/MACI Generic MethodCellsgrown on monolayer with patients serumHarvest 200-300mg full thickness cartilage from trochlea (non load bearing)No. cells x 20-30Under inert collagen membrane (ACI)On inert collagen membrane (MACI)
- 65.
- 66. Treatment with CARTICELUses your own cartilage cells (chondrocytes) to repair the articular cartilage damage in your knee. When implanted into a cartilage injury, your own cells can form new cartilage; this new cartilage is very similar to your original cartilage. The CARTICEL implantation procedure is called AutologousChondrocyte Implantation or ACI. It is a two-step process. Step 1: BiopsyKnee Cartilage Arthroscopy and BiopsyDuring an arthroscopic procedure, surgeon assesses the extent of cartilage damage & pt. as a candidate for CARTICEL implantation
- 67. “Biopsy” ofhealthy tissue about the size of a pencil eraser i.e. about 200 -300 mg.
- 68. From outer edgeof sup. Med. or lat. Femoral condyle or inner edge of lat. Femoral condyle at the intercondylar notch.
- 69. This sample issent to product labs.Biopsy can be stored for up to two years, so you can schedule your surgery at your convenience.
- 70. When youare ready, your cells are cultured ; over three to five weeks they increase to approx. 12 million cells in a vial containing 0.3 – 0.4 cc of medium.
- 71. Every step ofthe manufacturing process is monitored to ensure high quality and safety. CARTICEL Manufacturing and Delivery
- 72. Step 2: ImplantationCartilageInjury CleanedDuring this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette, leaving only healthy tissue.
- 73. Biomachenicalallignment procedures ifrequired should be done in conjunction with implantation.CARTICEL Implantation
- 74. Periosteal Patchsurgeon takesa small piece of tissue from your shin bone and sews it securely over the injury.CARTICEL Implantation surgeon injects CARTICEL under the patch.When CARTICEL is surgically implanted into a cartilage injury, it can grow and form new hyaline-like cartilage, with properties similar to those of the original cartilage. Repairing the injury helps to reduce pain and improve movement and function.
- 77.
- 78. MACI MethodCultured chondrocytesseeded in bilayeredtypeI/III collagen membraneImplanted using fibrin glueMatrix remodelled in months, replaced by extracellular matrix regenerate
- 79. ComplicationsThe overall failurerate is at present quoted as being 10%.
- 80. The two mostcommon complications include :
- 81. loosening of thetransplant tissue,
- 82. formation of fibroustissue at the repair site and adhesions with return of pain and locking.
- 83. Neither of thesecomplications usually leaves the patient in a worse condition than his/her pre-transplantation state.
- 84. Other adverse eventsinclude :
- 85. post-op haematoma (bigblood clot)
- 86. hypertrophic synovitis (angryknee) and superficial wound infection.ASSESMENT OF TECHNIQUE :Improvements in ClinicalOutcome:: FOLLOW UP results
- 87.
- 88.
- 89.
- 90.
- 91.
- 92.
- 93.
- 94.
- 95.
- 96.
- 97.
- 98. Final appearance oftheperiosteum sutured overfemoral condyle defect. Thecartilage cells have beeninjected under the flap and thefinal suture placed to close the"cover" and provide a watertightseal.FOLLOW UP: ARTHROSCOPICArthroscopic appearance of thesame area 12 months afterCarticel™ implantation. Thedefect is no longer visible andthere is now hyaline cartilage(biopsy proven) filling theoriginal defect site.
- 99. Rehabilitation guidelinesImmobilization: first12-24 hours(CPM): after 12-24 hours, for about 4 weeksComplete joint loading: from about 5th week trochlea/patellafrom about 8th week condyleBack to sports: Low impact -> within 6 monthsRepeated impact -> from 8th monthHigh impact -> from 10-12th month
- 100. ACI RehabilitationWeight bearingItis recommended to keep you in non-weight bearing until the second week after surgery (ACI). You can increase the weight bearing gradually and you may be able to sustain your full weight bearing after 6 to 12 weeks from surgery.Range of motionRecovery on your ROM (Range of Motion) is gradually increased with a continuous passive motion (CPM) machine and may be completed to 140 degrees of ROM at 6 weeks to 12 weeks after surgery
- 101. ACI RehabilitationIndoor exerciseYoucan strenghthen your muscles surrounding the knee joint with a four point exercise, as well as isometric, hamstring and squatting exercises, from 4 weeks to 6 weeks after surgery.You may start performing stationary bike activity without resistance and increase the resistance gradually.Outdoor exerciseAt 13 weeks after surgery you can start walking lightly and at 10 months after surgery you can perform jogging and then you may enjoy intensity exercise like playing tennis or volleyball from 18 months after surgery. Rehabilitation Goals at 12 weeks after ACIFull ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control
- 102. COMPARISON WITH OTHERMETHODS OF TREATMENTS :AutologousChondrocyte Implantation Aims to increase the best condition for cartilage defect.Advantages:Hyaline cartilage is formed
- 103.
- 104.
- 105. With Fourth Generation ACI:Useof cell – gel mixture (collagen, hyaluronic acid and fibrin) has fast gelling properties (1 – 5 min) upon transplantation
- 106. No membrane orperiosteal patch
- 107. Minimal surgical exposureand reduced surgery time.
- 108. Corrects evenly irregulardefect shapes
- 109. Applicable to largerdefects
- 110. COMPARISON WITH OTHERMETHODS OF TREATMENTS……….Abrasion arthroplastyAims to decrease the inflammation of the joint.Disadvantages:Removes many cartilage fragments from the joint
- 111. Symptoms reoccur within one yearDrilling and MicrofractureAims to generate a healing response.Disadvantages:The healing response in inadequate
- 112. No hyaline cartilageis formed, but rather fibrocartilage
- 113. Has a limitedlifespan of approximately one year
- 114. Rapid deterioration aftersuch procedures can be expectedCOMPARISON WITH OTHER METHODS OF TREATMENTS……….Perichondral ResurfacingDisadvantages:Isolated cartilage defects are often too large to be covered byhperichondrum
- 115. Long term follow-upof such procedures indicate that the implants undergo endochondral ossificationSynthetic Materials (i.e. Carbon Fiber Mesh)Disadvantages: It often results in fibrous tissue formation
- 116.
- 117. Often the causefor synovitis in the jointsOsteocartiloginous GraftsAims to reconstruct joints.Disadvantages:Unless fresh cartilage is transplanted, the cartilage is dead
- 118. Fresh grafts arenot commonly used, as they inevitably carry a risk of disease transmission
- 119. Cyropreserved grafts cansurvive for many years, but ultimately deteriorateResults of the Carticel™ procedure have been encouraging although it is not always successful. An analysis was done of the U.S. and Swedish registry of 153 consecutive patients undergoing this procedure with follow-up from 1 week to 94 months. The following results were obtained:
- 120.
- 121.
- 122.
- 123. Conclusions :ACI VsMACINo current evidence to justify aggressive treatment of asymptomatic lesions with ACI/MACI
- 124. Patients with fullthickness symptomatic defects do poorly if left untreated
- 125. ACI and MACIlead to significant improvement in objective and patient reported clinical outcome scores for up to ten years (even among those with previous failed marrow stimulation techniques)MACI has a superior rate of clinical improvement in comparison to ACI
- 126. Repair tissue mayremodel and improve in quality with time
- 127. ACI and MACIcomparable at 6 yearsRecent advances:HYAFF 3D matrixHYAFF biomaterialscontain high quantities ofderivatized HAHA-rich,chondrocyte compatibleembryonic-like mileuconductive to regenerativehealing patterns
- 128. • Non wovenfelt, 2 mm thick, fiber diameter 10 microns.• Chondrocytes are isolated, and passaged in culture on plasticdishes up to 3 weeks.• Cells are seeded for 2 weeks on HYAFF scaffold at a density of1 x 106 / cm2, resulting in a total of 4 x 106/ cm2 seeded cells pergraft.HYAFF-based Scaffold
- 129. CHONDRON™Uses a cell– gel mixture (includes collagen, hyaluronic acid and fibrin) that has fast gelling properties (1 – 5 min) upon transplantation.This cell and gel mixture enable even cell distribution three-dimensionally, moldable to fit irregular defect shape and applicable to a larger defect.Thus there is minimal surgical exposure and reduced surgery time. (three-dimensional reconstruction of a chondron from the growth plate of the murine long bone. the model was generated from multiple sections imaged in an electron microscope. plasma membranes are coloured green and internal organelles are visible within the top cell.)
- 130. RECOVERY TO HEALTHY ACTIVE LIFE
- 131.