Autologous chondrocyte implantation (ACI) is a worldwide recognized therapy to treat focal cartilage lesions. Here we describe the experiments followed by our group to develop a modification of MACI called High Density-Autologous Chondrocyte Implantation (HD-ACI) in which cell density is increased 5-fold.
In classical ACI, 5 million of cultured chondrocytes were implanted in the cartilage defect, but the use of periosteum increased morbidity. In MACI, 20 million cells are seeded in a 20 cm2 collagen membrane, so cartilage defects are treated with a density of 1 million cells per cm2. Surgeons observed that neo-formed tissue was softer than normal cartilage and had scarce cell number. We proposed to increase cell density to 5 million cells per cm2, and first of all we had to prove its safety and effectiveness in a sheep model. In these experiments, 1 million and 5 million chondrocytes as well as 5 million mesenchymal stem cells were tested in 1 cm2 defects performed in the cartilage of the medial femoral condyle. In all animals, we carried-out other cartilage defects that were repaired with microfractures.
Histological and molecular studies demonstrated that the animals treated with 5 million chondrocytes regenerated cartilage defects with a better hyaline cartilage than those treated with 1 million cells while fibrocartilage was produced in the animals treated with mesenchymal stem cells and in the defects treated with microfractures. Currently, 336 patients (251 in the knee, 82 in the ankle and 3 in the hip) have been treated with HD-ACI and in this work, we present the results of 176 treated in the knee and 48 in the ankle
Our results demonstrate that HD-ACI is a safe and effective technique for the treatment of cartilage defects, giving rise a neo-formed hyaline tissue and improving clinical and subjective perception of the joint functionality