Autologous Chondrocyte Transplantation

Dr. Babloo

Chondral Injuries

Commonly these injuries heal by scar tissue formation :

- Arthroscopic Debridement :- Arthroscopic lavage- Subchondral drilling- Microfracture Marrow stimulation techniques

- Abrasion arthroplasty to induce the growth of fibrocartilage into the chondral defect.

Treatment options

Stages of ACI healing

Healing process has several stages. They include the

• proliferative stage (0 to 6 weeks),

• the transition stage (7 to 12 weeks), and

• a remodeling and maturation stage which occurs over a prolonged period (13 weeks to 3 years)

Proliferative stage

• During this stage, a primitive cell response occurs with tissue fill of the defect and poor integration to underlying bone or adjacent cartilage.

• Mostly type I and some type II collagen is produced.

• The tissue is soft and jelly-like and easily damaged

Transition phase

• This marks the production of type II collagen framework and the early production of proteoglycans.

• The proteoglycans, which form the matrix, help imbibe water to give cartilage its viscoelastic properties.

• The tissue is not yet firm or well integrated and has the consistency of a firm gelatin.

• It is milkable when probed with an arthroscopic nerve hook, indicating incomplete integration to underlying bone

Stage of remodeling and maturation

• The matrix proteins cross-link and stabilize in large aggregates.

• The collagen framework reorganizes so as to integrate into the subchondral bone and form arcades of Benninghoff.

• Usually by 4 to 6 months, the tissue has firmed up to a putty-like consistency and is integrated to the underlying bone

• At this stage, patients experience good symptom relief

• During this stage excessive activity may cause repair tissue degeneration or continued improvement in remodeling

• Hence, the concept of a time course of healing is critical during the rehabilitation phase of ACT

Indications for ACT

• Symptomatic full-thickness chondral injury of the femoral articular surface (femoral weight-bearing condyles and sulcus or trochlea) in a physiologically young (<45 years) patient who is compliant with the rehabilitation protocol

• osteochondritis dissecans (OCD)

• Results of chondral injuries of the patella and tibia (improved in 70% to 80% of patients) are not as consistently high as those of the femoral weight-bearing condyles and trochlea (85% to 90% improved)

• ACT is not FDA approved as a treatment for OA, that is, bipolar chondral injuries with radiographic weight-bearing joint space loss

Pre-requisites for surgery

• Appropriate biomechanical alignment

• Ligamentous stability

• Range of motion

Not recommended for patients who have :

• an unstable knee

• in children

• in any joint other than knee.

Clinical examination

• Assessing subtle PF maltracking is important because this may become more pronounced and symptomatic after arthrotomy, which may adversely affect the treatment outcome of a trochlea or patellar ACT

• Assessment of predisposing factors for cartilage injury and degeneration may affect the prognostic outcome.

• These may include cruciate ligament insufficiency, genu varus or valgus, obesity, bone deficiency (AVN, OCD, and degenerative or ganglion bone cysts), inflammatory arthropathy, and familial osteoarthropathy

• These must be assessed so that they may be either corrected in a staged or concomitant fashion with ACT

Investigations

Wt bearing xray and skyline views

• Evidence of joint space narrowing 50% with osteophyte formation, subchondral bony sclerosis or cyst formation eliminates patients from treatment (ie, if bone on bone changes are present)

MRI

MRI scanning, while helpful for soft-tissue evaluation of meniscal or ligamentous injury as well as assessment of bone bruises and osteonecrosis, does not have a high sensitivity and specificity (75% to 93%) for determining the extent of a chondral injury or subtle chondromalacia changes.

The gold standard for determining whether a symptomatic patient is a candidate for ACT are normal radiographs, accompanied by an arthroscopic assessment showing focal pathology

A’scopy and Cartilage Biopsy

• Extent of lesion, Menisci, AP length of lesion

• Quality and thickness of the surrounding articular cartilage will determine whether healthy cartilage will be available for periosteal suturing or a non-contained chondral injury will require suturing through synovium or small drill holes through the bone.

• The most commonly chosen site for biopsy is the superior medial edge of the trochlea

• Superior lateral femoral condyle

• lateral intercondylar notch

• superior transverse trochlea margin adjacent to the supracondylar synovium

• Approximately 200 to 300 mg of articular cartilage (approximately 5 mm wide and 1 cm long) is required for enzymatic digestion for cell culturing.

• This contains approximately 2 to 3 lakh cells, which may be enzymatically digested and grown to approximately 120 lakh cells per 0.4 mL of culture media per implantation vial.

• After in-vitro expansion of cells 3 to 5 weeks later, a suitable number and volume of cells (usually one vial per each 4 to 6 sq cm defect) will be grown to accommodate the defect size required

• Can be stored upto 2 years

Implantation of Autologous Chondrocytes

Open implantation include arthrotomy, defect

preparation, periosteum procurement from the tibia or femur, periosteum fixation, periosteum water-tight integrity testing, autologous or allogeneic fibrin glue sealant, chondrocyte implantation and wound closure

MACI

• Matrix induced ACI

• Cultured chondrocytes seeded in bilayered typeI/III collagen membrane

• Implanted using fibrin glue

Rehabilitation goals

● Aggressive ROM exercises to enhance chondrocyte regeneration and decrease the likelihood of intraarticular adhesions

●Touch-weight bearing for 6 wks and full by 12 weeks to prevent periosteal overload and central degeneration or delamination of a weight bearing graft

● Isometric and gentle functional muscle exercises to regain muscle tone and prevent atrophy

• CPM is instituted as soon as cell attachment has occurred, usually 6 hours after surgery

• This is utilized for approximately 6 to 8 hours daily for up to 6 weeks after surgery

• Initially it is used for a range of 0° to 40° maximum. CPM from 40° to 70° is not recommended because maximal PF contact forces occur in this range.

• CPM for defects of trochlear defects is less vigorous

• The remainder of the motion is obtained by the patient dangling a leg over the edge of the bed to regain further motion

• On average, it takes 4 to 4 1/2 months for patients to discard their supports and walk comfortably

• Running is not permitted until graft hardness becomes similar to adjacent cartilage, which takes approximately 9 to 12 months

• Kneeling and squatting are not permitted until 12 to 18 months after surgery

• Osteochondritis dissecans may take 18 to 24 months.

Advantages

• Can produce hyaline-like cartilage.

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

• Moderate to large defects that have failed previous intervention.

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

• Expected outcome

• Return to previous level of functioning

Disadvantages

• More invasive

• Expense

• Longer recovery

• Overall failure rate is at present quoted as being 10%.

Complications

• Incomplete periosteal graft incorporation to host cartilage and hypertrophic graft edge response.

• Clinically, this usually manifests as a proliferative hypertrophic periosteal healing response between 3 and 7 months after surgery

• Intra-articular adhesions with resultant stiffness are uncommon

• Post-op hematoma, hypertrophic synovitis