DR. P .GUPTA (M.S.)</li></ul> SPEAKER :<br /> PRIYANK GUPTA<br />
THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TREATMENT OF ARTICULAR CARTILAGE DEFECTS IN THE KNEE JOINT <br />J. A. L. Hart; and J. Paddle<br />PURPOSE: To define the role of ACI in treatment of cartilagedefects in the knee joint.<br />METHOD: 106 articular cartilage defects in 79 knees of 77 patientswere treated by ACI as described by Brittberg et al, 1994. <br />-43.5%of the lesions involved the patella, <br />-35.2% the femoral condyles,<br />-16.7% the trochlea, and <br />-4.6% the tibial condyles. <br />-20% of kneeshad more than one defect. <br />Associated biomechanical procedureswere carried out in 88.7%.<br />
RESULTS:ASSESSEDARTHROSCOPICALLY 9 MONTHS AFTER IMPLANTATION<br /><ul><li>70 lesions in 58 knees and 56 patients
The average ICRS repair score (maximum 12)was as follows:</li></ul>-Tibialcondyle 11.5 (4 defects); <br />-Patella 11.3(32 defects); <br />-Femoral condyle 11.0(23 defects) <br />-Trochlea10.7 (11 defects). <br /><ul><li>Synovitis was markedly reduced in all kneeswith well healed defects.
Contraindications to ACI in this serieswere:</li></ul>-Non-contained defects-Bi-polar lesions,-Patients greaterthan 45 years,-Uncorrected biomechanics,-Regional pain syndrometype 1,-Limited joint movement,-Defective subchondral boneplate.<br />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.<br />
AUTOLOGOUS CHONDROCYTE GRAFTS: MULTICENTRIC TRIAL WITH 28 KNEE IMPLANTATIONS WITH MORE THAN TWO YEARS FOLLOW-UP<br />Journal of Bone and Joint Surgery - British Volume, Vol 90-B, Issue SUPP_II, 252<br />Purpose of the study: Spontaneous repair of lost deep chondraltissue is minimal in the knee joint. <br />A clinical trial of chondrocyteautografts as described by Brittberg and Peterson was undertakenby the Nantes University Hospital and the French Society ofArthroscopy in 1999.<br />
Material and methods: Twenty-eight patients,<br /> mean age 28 years,underwent surgery in eight centers.<br /> Etiologies were:<br />osteochondritis(n=14), <br />isolated posttraumatic chondorpathy (n=7), <br />chondropathyand full-thickness ACL tear (n=7). <br />All lesions involved thecondyles and were deep (ICRS grds 3 and 4).<br /> Mean surface areainvolved after debridement was 490 mm2 (range 150–1000mm2).<br /> Patients were followed three years after the autologousgrafting to assess functional outcome. <br />An MRI was obtained at2–3 years. <br />Thirteen control arthroscopy procedures wereperformed including<br /> eight with biopsy specimens for histologyand immunohisto-chemistry studies.<br />
RESULTS: Twenty-six patients were reviewed at > 2 yrs<br /><ul><li> There were no general complications,
Three patients presenteda partial avulsion of the graft treated by arthroscopy and oneunderwent arthrolysis at six months.
FUNCTION improved in allpatients except three and pain improved in all.
THE ICRS SCOREimproved from 43 points (range 19–70) to 77 points (range39–84).
Sixteen control MRIs were available and showedthat
Function score (r=0.78and MRI score (r=0.76) were correlated with arthroscopic sores.There was no correlation with the histological results.</li></ul>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.<br />
Provides resistance to tensile,compressive and shear forces
Acts as a smooth , efficient surface for motion. </li></li></ul><li>Hyaline Cartilage StructureThe “stuff” of cartilage:<br /><ul><li>Functions of the Articular Cartilage :</li></ul>– Distribute load<br />– Absorb shock<br />
Chondral Injuries:<br />Commonly these injuries heal by scar tissue formation :<br />
Prevalence and Incidence<br /><ul><li>993 consecutive arthroscopies – 66% articular cartilage pathology, 11% full thickness, localised lesions suitable for repair procedures</li></ul>Aroen A, Loken S, Heir S, et al. Am J Sports Med 2004; 32: 211-15<br /><ul><li>31000 arthroscopic procedures – 63% articular cartilage lesions</li></ul>Curl WW, Krome J, Gordon ES, et al. Arthroscopy 1997; 13: 456-60<br /><ul><li>1000 consecutive arthroscopies – 19% localised chondral/osteochondral lesions</li></ul>Hjelle K et al. Arthroscopy 2002; 18: 730-4<br />
Cartilage Injury Occurs in Many Forms<br /><ul><li>Trauma</li></ul>sports or work related<br /><ul><li>Chronic instability</li></ul>long term effects: ACL and other<br />meniscal deficiency<br /><ul><li>Mal-aligned joint - deformity</li></ul>varus / Valgus<br /><ul><li>OsteochondritisDissecans [OCD]
MicrofractureMARROW STIMULATION </li></ul> TECHNIQUES<br /><ul><li>Abrasion arthroplasty</li></ul> -to induce the growth of fibrocartilage into the chondral defect. <br />(This fibrocartilage does not withstand shock or shearing force as well as the original hyaline cartilage, and may deteriorate over time.)<br />
SO IT LED US TO SEARCH OF MORE PROMISING OPTION :<br />AUTOLOGUS <br /> CHONDROCYTE <br /> IMPLANTATION<br />
AutologousChondrocyte Implantation (ACI) :BACKGROUND<br /><ul><li>JBJS [Am], 1987 Peterson et al, Gothenburg,– first application of cell engineering in orthopaedics
Treatment with CARTICEL <br />Uses 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. <br />Step 1: Biopsy<br />Knee Cartilage Arthroscopy and Biopsy<br /><ul><li>During an arthroscopic procedure, surgeon assesses the extent of cartilage damage & pt. as a candidate for CARTICEL implantation
“Biopsy” of healthy tissue about the size of a pencil eraser i.e. about 200 -300 mg.
From outer edge of sup. Med. or lat. Femoral condyle or inner edge of lat. Femoral condyle at the intercondylar notch.
This sample is sent to product labs.</li></li></ul><li><ul><li>Biopsy can be stored for up to two years, so you can schedule your surgery at your convenience.
When you are 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.
Every step of the manufacturing process is monitored to ensure high quality and safety. </li></ul>CARTICEL Manufacturing and Delivery<br />
Step 2: Implantation<br />Cartilage Injury Cleaned<br /><ul><li>During this second stage arthrotomy done to expose knee and any dead or damaged tissue from the injury removed with curette, leaving only healthy tissue.
Biomachenicalallignment procedures if required should be done in conjunction with implantation.</li></li></ul><li>CARTICEL Implantation<br />
Periosteal Patch<br />surgeon takes a small piece of tissue from your shin bone and sews it securely over the injury.<br />CARTICEL Implantation<br /> 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. <br />Repairing the injury helps to reduce pain and improve movement and function.<br />
Final appearance of the<br />periosteum sutured over<br />femoral condyle defect. The<br />cartilage cells have been<br />injected under the flap and the<br />final suture placed to close the<br />"cover" and provide a watertight<br />seal.<br />FOLLOW UP: ARTHROSCOPIC<br />Arthroscopic appearance of the<br />same area 12 months after<br />Carticel™ implantation. The<br />defect is no longer visible and<br />there is now hyaline cartilage<br />(biopsy proven) filling the<br />original defect site.<br />
Rehabilitation guidelines<br />Immobilization: first 12-24 hours<br />(CPM): after 12-24 hours, for about 4 weeks<br />Complete joint loading: <br />from about 5th week trochlea/patella<br />from about 8th week condyle<br />Back to sports: Low impact -> within 6 months<br />Repeated impact -> from 8th month<br />High impact -> from 10-12th month<br />
ACI Rehabilitation<br />Weight bearing<br />It is 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.<br />Range of motion<br />Recovery 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<br />
ACI Rehabilitation<br />Indoor exercise<br />You can 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.<br />You may start performing stationary bike activity without resistance and increase the resistance gradually.<br />Outdoor exercise<br />At 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. <br />Rehabilitation Goals at 12 weeks after ACI<br />Full ROM (Range of Motion) <br />Minimal edema level <br />Minimal occasional pain <br />Pain free tolerance to transitional phase exercise with adequate stability and motor control<br /> <br />
COMPARISON WITH OTHER METHODS OF TREATMENTS :<br />AutologousChondrocyte Implantation <br />Aims to increase the best condition for cartilage defect.<br />Advantages:<br /><ul><li>Hyaline cartilage is formed
Applicable to larger defects</li></ul> <br />
COMPARISON WITH OTHER METHODS OF TREATMENTS……….<br />Abrasion arthroplasty<br />Aims to decrease the inflammation of the joint.<br />Disadvantages:<br /><ul><li>Removes many cartilage fragments from the joint
Symptoms reoccur within one year</li></ul>Drilling and MicrofractureAims to generate a healing response.<br />Disadvantages:<br /><ul><li>The healing response in inadequate
No hyaline cartilage is formed, but rather fibrocartilage
Has a limited lifespan of approximately one year
Rapid deterioration after such procedures can be expected</li></li></ul><li>COMPARISON WITH OTHER METHODS OF TREATMENTS……….<br />Perichondral ResurfacingDisadvantages:<br /><ul><li>Isolated cartilage defects are often too large to be covered byhperichondrum
Long term follow-up of such procedures indicate that the implants undergo endochondral ossification</li></ul>Synthetic Materials (i.e. Carbon Fiber Mesh)<br />Disadvantages:<br /><ul><li> It often results in fibrous tissue formation
Often the cause for synovitis in the joints</li></ul>Osteocartiloginous GraftsAims to reconstruct joints.<br />Disadvantages:<br /><ul><li>Unless fresh cartilage is transplanted, the cartilage is dead
Fresh grafts are not commonly used, as they inevitably carry a risk of disease transmission
Cyropreserved grafts can survive for many years, but ultimately deteriorate</li></li></ul><li><ul><li>Results 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:
Good or Excellent results at 2 years</li></ul>persisting at 5 years post-op 97%<br /><ul><li>Thus, a total of 85% of patients showed some or complete improvement with the</li></ul>implantation technique. The Carticel procedure demonstrated good durability at 5-10 years out.<br />CONCLUSIONS<br />
Conclusions :ACI Vs MACI<br /><ul><li>No current evidence to justify aggressive treatment of asymptomatic lesions with ACI/MACI
Patients with full thickness symptomatic defects do poorly if left untreated
ACI and MACI lead to significant improvement in objective and patient reported clinical outcome scores for up to ten years</li></ul> (even among those with previous failed marrow stimulation techniques)<br /><ul><li>MACI has a superior rate of clinical improvement in comparison to ACI
Repair tissue may remodel and improve in quality with time
ACI and MACI comparable at 6 years</li></li></ul><li>Recent advances:HYAFF 3D matrix<br />HYAFF biomaterials<br />contain high quantities of<br />derivatized HA<br />HA-rich,<br />chondrocyte compatible<br />embryonic-like mileu<br />conductive to regenerative<br />healing patterns<br />
• Non woven felt, 2 mm thick, fiber diameter 10 microns.<br />• Chondrocytes are isolated, and passaged in culture on plastic<br />dishes up to 3 weeks.<br />• Cells are seeded for 2 weeks on HYAFF scaffold at a density of<br />1 x 106 / cm2, resulting in a total of 4 x 106/ cm2 seeded cells per<br />graft.<br />HYAFF-based Scaffold<br />
CHONDRON™<br />Uses a cell – gel mixture (includes collagen, hyaluronic acid and fibrin) that has fast gelling properties (1 – 5 min) upon transplantation.<br />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. <br />(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.)<br />