Stabilized Autologous Fibrin-Chondrocyte Constructs for Cartilage Repair in Vivo

Abstract

Stabilization of fibrin-chondrocyte constructs with fibrinolytical inhibitors has been shown to be a feasible method for the reconstruction of cartilage in vitro. In this study, the method was tested in vivo. Autologous cultures were used to form stabilized fibrin-chondrocyte constructs that were injected into auricular cartilage defects of rabbits. Stabilization was achieved by high doses of fibrinolytic inhibitors. Samples were prepared for magnetic resonance imaging, histology, and immunohistochemistry after 1, 2, 4, and 6 months. Defects of the contralateral ear, which were treated with stabilized fibrin without cells, were used for controlled comparisons. In all cell-fibrin samples, cartilage-like tissue was present. Immunohistochemistry revealed the presence of collagen II. This finding was similar for all observations. In the control samples, only minor new cartilage could be detected at the cut edges. The reconstruction of cartilage in vivo by injecting fibrin-chondrocyte constructs, stabilized with inhibitors of fibrinolysis, is thus possible.

Effects of Fibrinolytic Inhibitors on Chondrogenesis of Bone-marrow Derived Mesenchymal Stem Cells in Fibrin Gels

“…Fibrin gels have already been used in cardiovascular and thoracic surgery and as a delivery system for drugs. They have also been proven successful in the transplantation of chondrocytes (Fortier et al 2002;Fussenegger et al 2003;Hendrickson et al 1994, Nixon et al 1999Westreich et al 2004). Although the fibrin gel is a natural scaffold with many advantages, its main drawback is fibrinolysis.…”

“…In addition, fibrin gels can be produced into an injectable, moldable form minimizing invasive implantation (Passaretti et al 2001;Silverman et al 1999;Westreich et al 2004;Xu et al 2004). Previous studies have also shown that fibrin gels are capable of supporting cartilage formation of chondrocytes (Fortier et al 1997(Fortier et al , 1998(Fortier et al , 2002Fussenegger et al 2003, Hendrickson et al 1994Nixon et al 1999;Meinhart et al 1999;Passaretti et al 2001;Silverman et al 1999;Sims et al 1998;Westreich et al 2004;Xu et al 2004) and chondrogenic and osteogenic transformation of mesenchymal stem cells (Bensaid et al 2003;Worster et al 2001). However, fibrin is intrinsically unstable due to fibrinolysis.…”

Bioactive Scaffolds for the Controlled Formation of Complex Skeletal Tissues

“…Wang et al, 2010a;W. Wang et al, 2010b), or by the use of enzymatic inhibitors (Fussenegger et al, 2003). Eyrich et al reported some optimized conditions that lead to fibrin gels that were stable for up to three weeks in vitro (Eyrich et al, 2007).…”

Peptide-Based Materials for Cartilage Tissue Regeneration

“…Alginate and agarose are polysaccharide biomaterials that originate from seaweed and show good biocompatibility and cytocompatibility; however, their poor degradation kinetics and limited potential for functional modification limits their clinical use (Murphy and Sambanis 2001). Fibrin is another natural scaffold that is derived from blood and has been shown to modulate cartilage formation in vivo by facilitating the adhesion of chondrocytes (Fussenegger et al 2003). Nevertheless, fibrin is mechanically inadequate for cartilage tissue engineering, and its degradation rate is unstable.…”