| Chondrocyte-based tissue engineering methods, including cell transplantation alone or within a scaffold, are emerging therapies for articular cartilage repair. One hypothesized mechanism for repair is that transplanted chondrocytes are retained within the defect, synthesize and deposit cartilaginous matrix to fill the defect, and integrate the newly-formed tissue with surrounding host tissue. The overall objective of this research is to provide an improved understanding of chondrocyte adhesion and matrix metabolism following transplantation to cartilage.; Receptor mediated adhesion to the surrounding cartilage extracellular matrix may provide an initial mechanism to stabilize transplanted chondrocytes within the defect. The adhesion of transplanted chondrocytes to surrounding host cartilage may be mediated by receptors including integrins, CD44, and annexin V. Rapid screening and shear flow adhesion assays were developed to quantify and characterize adhesion of bovine and human chondrocytes to cartilage in a transplantation-type procedure. Adhesion to cartilage was mediated by β1-integrins, specifically α5β1, and αvβ5. CD44, annexin V αl-, α3-, and αvβ3-integrins did not function to mediate firm attachment, even though these receptors were present on the cell surface. Delineation of the mechanisms of adhesion may have clinical implications by allowing cell manipulations or matrix treatments to enhance chondrocyte adhesion, retention and subsequent function.; In chondrocyte transplantation procedures, the metabolism of chondrocytes at the host cartilage interface may be particularly important for cartilage repair. Culture of chondrocytes in alginate gels allows recovery of cells with an associated matrix which may foster retention of newly synthesized matrix. Using an in vitro model of chondrocyte transplantation, the effect of cell-substrate interactions and a cell-associated matrix on the synthesis, deposition, and release of matrix was investigated. The substrate onto which the chondrocytes were transplanted had a significant effect on metabolism, with cells on cartilage synthesizing and retaining less glycosaminoglycan and protein than cells on tissue culture plastic. In general, chondrocytes recovered from alginate culture synthesized more glycosaminoglycan and protein following transplantation than did monolayer cultured chondrocytes. These patterns of matrix metabolism by transplanted cells have implications for repair. Regulation of chondrocyte function with culture conditions and matrix interactions may be useful for cartilage tissue engineering. |
