Adhesion of tissue-engineered cartilage to native cartilage

Reconstruction of cartilaginous defects to correct both craniofacial deform ities and joint surface irregularities remains a challenging and controvers ial clinical problem. It has been shown that tissue-engineered cartilage ca n be produced in a nude mouse model. Before tissue-engineered cartilage is used clinically to fill in joint defects or to reconstruct auricular or nas al cartilaginous defects, it is important to determine whether it will inte grate with or adhere to the adjacent native cartilage at the recipient site . The purpose of this study was to determine whether tissue-engineered cart ilage would adhere to adjacent cartilage in vivo. Tissue-engineered cartilage was produced using a fibrin glue polymer (80 mg /cc purified porcine fibrinogen polymerized with 50 U/cc bovine thrombin) m ixed with fresh swine articular chondrocytes. The polymer/chondrocyte mixtu re was sandwiched between two 6-mm-diameter discs of fresh articular cartil age. These constructs were surgically inserted into a subcutaneous pocket o n the backs of nude mice (n = 15). The constructs were harvested 6 weeks la ter and assessed histologically, biomechanically, and by electron microscop y. Control samples consisted of cartilage discs held together by fibrin glu e alone (no chondrocytes) (n = 10). Histologic evaluation of the experimental constructs revealed a layer of ne ocartilage between the two native cartilage discs. The neocartilage appeare d to fill all irregularities along the surface of the cartilage discs. Safr anin-O and toluidine blue staining indicated the presence of glycosaminogly cans and collagen, respectively. Control samples showed no evidence of neoc artilage formation. Electron microscopy of the neocartilage revealed the fo rmation of collagen fibers similar in appearance to the normal cartilage ma trix in the adjacent native cartilage discs. The interface between the neoc artilage and the native cartilage demonstrated neocartilage matrix directly adjacent to the normal cartilage matrix without any gaps or intervening ca psule. The mechanical properties of the experimental constructs, as calcula ted from stress-strain curves, differed significantly from those of the con trol samples. The mean modulus for the experimental group was 0.74 +/- 0.22 MPa, which was 3.5 times greater than that of the control group (p < 0.000 2). The mean tensile strength of the experimental group was 0.064 +/- 0.024 MPa, which was 62.6 times greater than that of the control group (p < 0.00 02). The mean failure strain of the experimental group was 0.16 +/- 0.061 p ercent, which was 4.3 times greater than that of the control group (p < 0.0 002). Finally, the mean fracture energy of the experimental group was 0.000 49 +/- 0.00032 J, which was 15.6 times greater than that of the control gro up. Failure occurred in all cases at the interface between neocartilage and native cartilage. This study demonstrated that tissue-engineered cartilage produced using a f ibrin-based polymer does adhere to adjacent native cartilage and can be use d to join two separate pieces of cartilage in the nude mouse model. Cartila ge pieces joined in this way can withstand forces significantly greater tha n those tolerated by cartilage samples joined only by fibrin glue.