Blood and cartilage: friend or foe?

Introduction: Blood has been considered an armful factor for the articular cartilage. Previous studies have demonstrated that recurrent intra-articular bleedings represent a negative factor for articular cartilage, inducing a deterioration of the tissue. This could ultimately lead to degenerative osteoarthritis, even though the mechanism is not yet entirely understood (1-3). Other authors have investigated the effect of peripheral blood on articular cartilage both in vitro and in vivo: Roosendal and Hooiveld have shown that a shortterm exposure of human articular cartilage to whole blood in vitro induced an irreversible dose-dependent inhibition of proteoglycan synthesis and it was accompanied by cell apoptosis (4,5). However, when a short-term exposure was performed in vivo after injection of autologous blood into the canine knee, the initially adverse changes in cartilage proteoglycan synthesis turned into normalization after 10 weeks (6). Recently, the same group has tested the threshold of blood exposure time and concentration that lead to irreversible joint damage (7). However, many current surgical procedures for articular cartilage repair, like subchondral bone drilling (8), abrasion artrhoplasty (9) and microfracture (10), are based on the capacity of bone marrow cells to produce a fibrocartilaginous tissue when migrated in a joint environment (11). In contrast, in the performance of the techniques based on the transplantation of autologous chondrocytes, the presence of blood has been considered a disturbing factor for the development of the new cartilage tissue (12). The more recent techniques for cartilage repair and reconstruction utilize autologous chondrocytes seeded onto a biocompatible scaffold, in which they can duplicate, mature and produce new cartilage matrix in vitro and in vivo after surgical implantation. Also in this approach, it is recommended care in protecting the reparative cells from the contact with blood, which could derive from the subchondral bone or any other part of the joint injured during the surgical implantation (13), both in open and arthroscopic approach. However, the nature of engineered cartilage differs from that of cartilage explants examined in the studies mentioned above. Therefore, we believe that the influence of the contact of peripheral blood to the engineered cartilage represents an important but still unclear issue that needs to be investigated. The engineered cartilage, however, is structurally and biologically different from native articular cartilage, as it is supposed to complete the maturation in vivo. Therefore, it is probably more susceptible to the adverse effects of an articular bleeding, as indicated by studies of other authors, who investigated the effect of blood on immature joint (14). The effect of blood on engineered cartilage was only recently investigated (15). We have developed an in vitro model to investigate the effect of blood contact on the tissue-engineered implant and demonstrated that a 3-day exposure of cartilage to 50% (volume/ volume) blood results in a temporary and reversible effect on engineered cartilage tissue obtained from chondrocytes seeded onto collagen scaffold. However, some important issues remain to be clarified: could the different blood concentration negatively affect the chondrocytes’ vitality and synthetic properties? Is the negative effect of blood on the engineered cartilage due to the toxic effect of the peripheral blood or to the lack of nutrients occurring during the exposure to blood? The aim of this study was to investigate the effect of different concentrations of blood and of the lack of nutrients on the morphological, biochemical and biomechanical properties of engin