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Orthopaedic Surgery Cartilage Repair
Articular Cartilage Engineering with Autologous Chondrocyte Transplantation
a report by
Mats Brittberg
Associate Professor, Cartilage Research Unit, Gothenburg University and Department of Orthopaedics, Kungsbacka Hospital
Tissue engineering is an emerging discipline that uses a combination The Technique
of cells, engineering materials and different biochemical factors to Chondrocytes are isolated from small slices of cartilage harvested
improve or replace deficient biological functions. The poor repair transarthroscopically from a minor weight-bearing area in the injured
capacity of articular cartilage after injury has led to many attempts to knee. The extracellular matrix is removed by enzymatic digestion and the
improve the repair of injured articular cartilage surfaces during the last cells are expanded in monolayer culture. The expansion of chondrocytes
50 years. The first example of clinical cartilage tissue engineering was in vitro is a selection of a limited number of chondrocyte progenitor
performed in 1987 when a knee with an articular cartilage defect on clones; the culture process allows the cells to revert to a foetal-like stage
the femoral condyle was treated by implanting the patient’s own and by this process the chondrocytes are believed to mimic the early
chondrocytes that had been expanded in vitro and then implanted into stages of mesenchymal condensation and tissue differentiation.
13
the defect in combination with a covering mechanical membrane – the
periosteum.
1
This, the first generation of chondrocyte transplantations, The primary goal of in vitro chondrocyte manipulation is to increase the cell
was initially termed autologous chondrocyte transplantation (ACT). number. Once a suitable number of cells is reached, the increased number
Today, the technique is called either ACT or autologous chondrocyte of chondrocytes is suspended in culture medium and then implanted into
the area of cartilage defect using a membrane over the defect as a method
of cell containment. In patients with small cartilage defects, ACT is mostly
Chondrocytes are isolated from small employed after failure of other techniques after six months. In large
slices of cartilage harvested
defects, ACT (up to 4cm
2
) may be used immediately as such large defects
are difficult to resurface with bone marrow stimulation techniques.
transarthroscopically from a minor
weight-bearing area in the injured knee.
Clinical Follow-ups
In a clinical evaluation of 244 patients with two to 10 years’ follow-up,
subjective and objective improvements were seen in high numbers of
implantation (ACI) and there exist many modifications of the patients with femoral condyle lesions and osteochondritis dissecans.
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technique, from the first generation to now second and third There was a high percentage of good to excellent results (84–90%) in
generations of chondrocyte transplantation.
2-4
patients with different types of single femoral condyle lesions while other
types of lesions had a lower degree of success (mean 74%).
The initial surgical technique for ACI has been well described in several
reports.
5–8
The steps include an initial arthroscopically harvested cartilage To study the long-term durability of ACT-treated patients, 61 patients
biopsy from which chondrocytes can be isolated by enzymatic digestion who had passed two years post-surgery were followed for at least five
and, in in vitro culture, expanded to several times the initial number of years up to 11 years post-surgery (mean 7.4 years). After two years, 50
cells. In a clinical setting today, the aim is to implant a density of 30 x 106 out of 61 patients were graded good–excellent.
14
At the five to 11 years
cells/ml, or 2 x 106 cells per cm
2
. With the initial technique, implantation follow-up, 51 of the 61 were graded good–excellent. The total failure
consists of an arthrotomy, defect preparation, periosteal flap harvest, rate was 16% (10/61) at mean 7.4 years. All ACT failures occurred in the
fixation of periosteal flap to defect, securing a watertight seal with fibrin first two years and patients showing good to excellent improvement at
glue, implanting the chondrocytes and wound closure. two years had a high percentage of good results at long-term follow-up.
However, today the periosteum is often replaced by a resorbable Most reports on the use of ACT from other centres show similar figures
membrane such as collagen I/III membrane ChondroGide
9
or Restore
10
(De Puy, Warzaw, Indiana). Second-generation ACI are cell-seeded
membranes such as matrix-induced ACI (MACI)
11
(Genzyme Biosurgery,
Mats Brittberg works in the Orthopaedic Department of Kungsbacka Hospital and is an
Associate Professor at the Cartilage Research Unit at Gothenburg University in Sweden. He is
Boston, MA) and the third generation includes chondrocytes cultured in
President of the International Cartilage Repair Society and the Chair of European Society of
3-D matrices such as hyaluronic acid (Hyalograft-C) (Fidia, Italy).
12
Sports Traumatology, Knee Surgery and Arthroscopy 2000 Cartilage Committee. His research
for the last 20 years has been focused on cartilage repair, with a focus on cartilage
regeneration using in vitro expanded autologous chondrocytes. Today his main interest is the
In Sweden, ACT in combination with a periosteal graft has been used in
recently established European Connective Tissue Engineering Centre, a research collaboration
approximately 1,500 patients since October 1987 and worldwide
between Gothenburg Medical University and the institution of Polymer Technology, Chalmers
Technical University.
variants of ACT/ACI have been tried in around 20,000 patients. The use
of ACT is always considered alongside other techniques.
© TOUCH BRIEFINGS 2007 81
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