Repair of porcine articular cartilage defect with autologous chondrocyte transplantation

Abstract

Articular cartilage is known to have poor healing capacity after injury. Autologous chondral grafting remains the mainstay to treat well-defined, full-thickness, symptomatic cartilage defects. We demonstrated the utilization of gelatin microbeads to deliver autologous chondrocytes for in vivo cartilage generation. Chondrocytes were harvested from the left forelimbs of 12 Lee-Sung pigs. The cells were expanded in monolayer culture and then seeded onto gelatin microbeads or left in monolayer. Shortly before implantation, the cell-laden beads were mixed with collagen type I gel, while the cells in monolayer culture were collected and re-suspended in culture medium. Full-thickness cartilage defects were surgically created in the weight-bearing surface of the femoral condyles of both knees, covered by periosteal patches taken from proximal tibia, and sealed with a porcine fibrin glue. In total, 48 condyles were equally allotted to experimental, control, and null groups that were filled beneath the patch with chondrocyte-laden beads in gel, chondrocytes in plain medium solution, or nothing, respectively. The repair was examined 6 months post-surgery on the basis of macroscopic appearance, histological scores based on the International Cartilage Repair Society Scale, and the proportion of characteristic chondrocytes. Tensile stress-relaxation behavior was determined from uniaxial indentation tests. The experimental group scored higher than the control group in the categories of matrix nature, cell distribution pattern, and absence of mineralization, with similar surface smoothness. Both the experimental and control groups were superior to the null group in the above-mentioned categories. Viable cell populations were equal in all groups, but the proportion of characteristic chondrocytes was highest in the experimental group. Matrix stiffness was ranked as null > native cartilage > control > experimental group. Transplanted autologous chondrocytes survive and could yield hyaline-like cartilage. The application of beads and gel for transplantation helped to retain the transferred cells in situ and maintain a better chondrocyte phenotype.

Adult human articular chondrocytes in a microcarrier‐based culture system: expansion and redifferentiation

“…16 Microcarrier-cultivated porcine chondrocytes implanted into full-thickness porcine cartilage defects outperformed chondrocytes propagated in monolayers. 17 However, the putative advantage of leaving these cells on microcarriers during differentiation remains to be confirmed.…”

Innovative Strategies for Treatment of Soft Tissue Injuries in Human and Animal Athletes

“…Using another polymer as basis, the group hopes to go into clinical studies in 2010 [3]. Chiang et al [27] seeded chondrocytes into gelation microbeads mixed with a collagen type I gel. This enhanced repair in a porcine cartilage defect model, and the chondrocyte phenotype was maintained better than without the carrier.…”

Direct Use of Resorbable Collagen-Based Beads for Cell Delivery in Tissue Engineering and Cell Therapy Applications

“…For cell-based therapies, a bioreactor is not necessary but may be used to amplify the cell numbers for the therapy. Indeed, a key element for both approaches is that they normally require significant expansion of the replacement cells, which have typically been derived in low numbers from small biopsy samples (Brittberg et al, 1994;Chiang et al, 2005;Thissen et al, 2005). A consequence of this expansion is that there can be a significant loss in the quality of cells available for the procedure.…”

“…2A), which is the characteristic collagen of articular, hyaline cartilage (Mayne, 1989;Miller & Matukas, 1969) to type I collagen (Fig. 2B), which is a mechanically-inferior fibrocartilage (Chiang et al, 2005;Wegener et al, 2009). Type I collagen is the principal collagen of many tissues, including skin, bone, ligament and tendons.…”

“…In ACI a cartilage biopsy sample is taken from the patient that yields low numbers of chondrocytes, which then must be expanded several fold to give sufficient cells for the regeneration procedure. In ACI, the cell expansion takes place in monolayer culture and may take 21 days or longer (Brittberg et al, 1994;Chiang et al, 2005;Henderson et al, 2005). As a consequence, the majority, if not all, of the implanted cells are likely to have lost their chondrocyte characteristics.…”