1. journal club (22-10-09) topic : autologuschondrocyte implantation

3. DR. P .GUPTA (M.S.) SPEAKER : PRIYANK GUPTA

4. THE ROLE OF AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI) IN THE TREATMENT OF ARTICULAR CARTILAGE DEFECTS IN THE KNEE JOINT J. A. L. Hart; and J. Paddle PURPOSE: 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%.

6. 4 eligible patientswere not assessed.

8. Contraindications to ACI in 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-UP Journal of Bone and Joint Surgery - British Volume, Vol 90-B, Issue SUPP_II, 252 Purpose 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.

12. Three patients presenteda partial avulsion of the graft treated by arthroscopy and oneunderwent arthrolysis at six months.

13. FUNCTION improved in allpatients except three and pain improved in all.

14. THE ICRS SCOREimproved from 43 points (range 19–70) to 77 points (range39–84).

15. Sixteen control MRIs were available and showedthat

16. the graft was hypertrophic in eleven cases,

17. on level infour, and insufficient in one.

18. Marginal integration was goodin 11 cases and partial in five.

19. Subchondral integration wascomplete in ten cases and mediocre in six.

20. THE ARTHROSCOPICSCORE was nearly normal (score 8–11) in eight cases andabnormal in five (score 4–7).

21. THE HISTOLOGICAL CLASS accordingto Knutsen (hyaline richness) was:

22. one in group 1 (>60%),

23. three in group 2 (> 40%),

24. four in group 3 (<40%) and

25. onein group 4 (bony or fibrous tissue).

26. Function score (r=0.78and MRI 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.

28. Gives elasticity

29. Provides resistance to tensile,compressive and shear forces

31. Chondral Injuries: Commonly these injuries heal by scar tissue formation :

34. Genetic pre-disposition / earlyarthritis

37. Arthroscopic lavage

38. Subchondral drilling

40. SO IT LED US TO SEARCH OF MORE PROMISING OPTION : AUTOLOGUS CHONDROCYTE IMPLANTATION

43. Demanding Physical activities

44. Willing & capable of rehabilitation program

46. Ligamentousstabilty

48. patients sensitive to materials of bovine origins

49. allergic to the antibiotic gentamicin

50. in children

52. Can produce hyaline-like cartilage.

53. Can fill defects regardless of size with functional repair tissue.

54. Moderate to large defects that have failed previous intervention.

55. Repair tissue which matures , rather than deteriorates over time.

56. Expected outcome

58. More invasive

59. Expense

61. Porcine type I/III

62. Inert Seal

63. Resorbs in 3-4 months ACI MACI Techniques :

64. ACI/MACI Generic Method Cells grown on monolayer with patients serum Harvest 200-300mg full thickness cartilage from trochlea (non load bearing) No. cells x 20-30 Under inert collagen membrane (ACI) On inert collagen membrane (MACI)

65. ACI Method

67. “Biopsy” of healthy tissue about the size of a pencil eraser i.e. about 200 -300 mg.

68. From outer edge of sup. Med. or lat. Femoral condyle or inner edge of lat. Femoral condyle at the intercondylar notch.

70. 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.

71. Every step of the manufacturing process is monitored to ensure high quality and safety. CARTICEL Manufacturing and Delivery

74. Periosteal Patch surgeon takes a 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. Aci steps :summarised

78. MACI Method Cultured chondrocytes seeded in bilayeredtypeI/III collagen membrane Implanted using fibrin glue Matrix remodelled in months, replaced by extracellular matrix regenerate

80. The two most common complications include :

81. loosening of the transplant tissue,

82. formation of fibrous tissue at the repair site and adhesions with return of pain and locking.

83. Neither of these complications usually leaves the patient in a worse condition than his/her pre-transplantation state.

84. Other adverse events include :

85. post-op haematoma (big blood clot)

88. Alignment

89. Bone quality

90. MRI

91. Healing cartilage

92. Graft failure

93. Arthroscopy + probe

94. Graft integrity

95. Pressure

97. FOLLOW UP: MRI

98. Final appearance of the periosteum sutured over femoral condyle defect. The cartilage cells have been injected under the flap and the final suture placed to close the &quot;cover&quot; and provide a watertight seal. FOLLOW UP: ARTHROSCOPIC Arthroscopic appearance of the same area 12 months after Carticel™ implantation. The defect is no longer visible and there is now hyaline cartilage (biopsy proven) filling the original defect site.

99. Rehabilitation guidelines Immobilization: first 12-24 hours (CPM): after 12-24 hours, for about 4 weeks Complete joint loading: from about 5th week trochlea/patella from about 8th week condyle Back to sports: Low impact -> within 6 months Repeated impact -> from 8th month High impact -> from 10-12th month

100. ACI Rehabilitation Weight bearing 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. Range of motion 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

101. ACI Rehabilitation Indoor exercise 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. You may start performing stationary bike activity without resistance and increase the resistance gradually. Outdoor exercise 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. Rehabilitation Goals at 12 weeks after ACI Full ROM (Range of Motion) Minimal edema level Minimal occasional pain Pain free tolerance to transitional phase exercise with adequate stability and motor control

103. Permanent reconstructed cartilage tissue

104. Most valuable treatment

105. With Fourth Generation ACI:Use of cell – gel mixture (collagen, hyaluronic acid and fibrin) has fast gelling properties (1 – 5 min) upon transplantation

106. No membrane or periosteal patch

107. Minimal surgical exposure and reduced surgery time.

108. Corrects evenly irregular defect shapes

109. Applicable to larger defects

112. No hyaline cartilage is formed, but rather fibrocartilage

113. Has a limited lifespan of approximately one year

116. Not adequate biomechanically

118. Fresh grafts are not commonly used, as they inevitably carry a risk of disease transmission

120. Patients with clinical improvement 85%

121. Good or Excellent results 42%

124. Patients with full thickness symptomatic defects do poorly if left untreated

126. Repair tissue may remodel and improve in quality with time

128. • Non woven felt, 2 mm thick, fiber diameter 10 microns. • Chondrocytes are isolated, and passaged in culture on plastic dishes up to 3 weeks. • Cells are seeded for 2 weeks on HYAFF scaffold at a density of 1 x 106 / cm2, resulting in a total of 4 x 106/ cm2 seeded cells per graft. 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. THANK YOU