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Autologous chondrocyte implantation (ACI,
ATC code The Anatomical Therapeutic Chemical (ATC) Classification System is a drug classification system that classifies the active ingredients of drugs according to the organ or system on which they act and their therapeutic, pharmacological and chemical ...
) is a biomedical treatment that repairs damages in articular cartilage. ACI provides pain relief while at the same time slowing down the progression or considerably delaying partial or total
joint replacement Replacement arthroplasty (from Greek ''arthron'', joint, limb, articulate, + ''plassein'', to form, mould, forge, feign, make an image of), or joint replacement surgery, is a procedure of orthopedic surgery in which an arthritic or dysfunctional j ...
(
knee replacement Knee replacement, also known as knee arthroplasty, is a surgical procedure to replace the weight-bearing surfaces of the knee joint to relieve pain and disability, most commonly offered when joint pain is not diminished by conservative sources a ...
) surgery. The goal of ACI is to allow people suffering from
articular cartilage damage Cartilage structures and functions can be damaged. Such damage can result from a variety of causes, such as a bad fall or traumatic sport-accident, previous knee injuries or wear and tear over time. Immobilization for long periods can also result i ...
to return to their old lifestyle; regaining mobility, going back to work and even practicing sports again. ACI procedures aim to provide complete hyaline repair tissues for
articular cartilage repair Articular cartilage repair treatment is focused on the restoration of the surface of an articular joint's hyaline cartilage. Over the last few decades, surgeons and researchers have made progress in elaborating surgical cartilage repair intervent ...
. Over the last 20 years, the procedure has become more widespread and it is currently probably the most developed articular cartilage repair technique. The procedure fails in about 15% of people. __TOC__


Procedure

This cell based
articular cartilage repair Articular cartilage repair treatment is focused on the restoration of the surface of an articular joint's hyaline cartilage. Over the last few decades, surgeons and researchers have made progress in elaborating surgical cartilage repair intervent ...
procedure takes place in three stages. In a first stage, between 200 and 300 milligrams
cartilage Cartilage is a resilient and smooth type of connective tissue. In tetrapods, it covers and protects the ends of long bones at the joints as articular cartilage, and is a structural component of many body parts including the rib cage, the neck an ...
is sampled arthroscopically from a less
weight bearing In orthopedics, weight-bearing is the amount of weight In science and engineering, the weight of an object is the force acting on the object due to gravity. Some standard textbooks define weight as a vector quantity, the gravitational force acti ...
area from either the intercondylar notch or the superior ridge of the medial or lateral femoral condyle of the patient. The matrix is removed enzymatically and the chondrocytes isolated. These cells are grown in vitro in a specialised laboratory for approximately four to six weeks, until there are enough cells to reimplant on the damaged area of the articular cartilage. The patient then undergoes a second treatment, in which the chondrocytes are applied on the damaged area during an open-knee surgery (also called arthrotomy). These autologous cells should adapt themselves to their new environment by forming new cartilage. During the implantation,
chondrocyte Chondrocytes (, from Greek χόνδρος, ''chondros'' = cartilage + κύτος, ''kytos'' = cell) are the only cells found in healthy cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteo ...
s are applied on the damaged area in combination with a membrane (tibial periosteum or biomembrane) or pre-seeded in a scaffold matrix.


Complications

The occurrence of subsequent surgical procedures (SSPs), primarily arthroscopy, following ACI is common. For example, in the Study of the Treatment of Articular Repair (STAR), 49% of Carticel ACI patients underwent an SSP on the treated knee, during the 4-year follow up. The most common serious adverse events (up to 5% of patients), include
arthrofibrosis Arthrofibrosis (from Greek: ''arthro-'' joint, ''fibrosis'' – scar tissue formation) has been described in most joints like knee, hip, ankle, foot joints, shoulder (frozen shoulder, adhesive capsulitis), elbow (stiff elbow), wrist, hand joints as ...
and joint adhesions, graft overgrowth,
chondromalacia Chondromalacia patellae (also known as CMP) is an inflammation of the underside of the patella and softening of the cartilage. The cartilage under the kneecap is a natural shock absorber, and overuse, injury, and many other factors can cause inc ...
or chondrosis, cartilage injury, graft complication, meniscal lesion, graft delamination, and osteoarthritis. Source: Carticel. A recent study from Germany, published in the November 2008 issue of the American Journal of Sports Medicine, analyzed 349 ACI procedures of the knee joint. Three different ACI techniques were used. A major proportion of complications after ACI can be summarized by 4 major diagnoses: symptomatic hypertrophy, disturbed fusion, delamination, and graft failure. Among those, the overall complication rate and incidence of hypertrophy of the transplant were higher for periosteum-covered ACI. Furthermore, an increased rate of symptomatic hypertrophy was found for patellar defects. Source: Philipp Niemeyer, MD, et al.: Characteristic Complications After Autologous Chondrocyte Implantation for Cartilage Defects of the Knee Joint. The American Journal of Sports Medicine 36:2091-2099 (2008).


Improvement of ACI

Techniques such as the EELS-TALC to enhance ACI and its next generation advancement called Matrix Assisted Chondrocyte Implantation (MACI) with enabling chondrocytes to be tissue engineered with long term native knee cartilage phenotype maintenance in vitro and in vivo, with the engineered tissue construct containing stem cell progenitors along with those expressing pluripotency markers and with added advantage of enriched hyaluronic acid (HA) expression by the cells have been reported which will contribute to improved regenerative therapies for cartilage damage.


References

{{Other drugs for disorders of the musculo-skeletal system Orthopedic surgical procedures