Inorganic-organic hybrid scaffolds for osteochondral regeneration

Ligament graft failure frequently results from poor integration of the replacement tissue with associated bone. Thus, the ability to regenerate the bone-ligament osteochondral interface would be advantageous in ligament reconstruction. At the osteochondral interface, the tissue transitions from a bone-like matrix to fibrocartilage. Therefore, a scaffold which promotes a spatially regulated transition in cell behavior from osteoblast-like to chondrocyte-like would be desirable. Previous research indicates that addition of inorganic components to organic scaffolds can enhance the deposition of bone-like matrix by associated osteoblasts. We therefore reasoned that a gradient in the inorganic content of a hybrid inorganic-organic scaffold may induce an osteochondral-like transition in cell phenotype and matrix production. To test this hypothesis, hydrogels were prepared from poly(ethylene glycol) (PEG) and star poly(dimethylsiloxane) (PDMSstar). As anticipated, both the matrix deposition and phenotype of encapsulated osteoblasts varied with scaffold inorganic content, although the directionality of this modulation was contrary to expectation. Specifically, osteoblasts appeared to trans-differentiate into chondrocyte-like cells with increasing scaffold inorganic content, as indicated by increased chondroitin sulfate and collagen type II production and by upregulation of sox9, a transcription factor associated with chondrocytic differentiation. Furthermore, the deposition of bone-like matrix (collagen type I, calcium phosphate, and osteocalcin) decreased with increasing PDMSstar content. The resistance of the PDMSstar-PEG scaffolds to protein adsorption and/or the changes in gel modulus/mesh structure accompanying PDMSstar incorporation may underlie the unexpected increase in chondrocytic phenotype with increasing inorganic content. Combined, the present results indicate that PDMSstar-PEG hybrid gels may prove promising for osteochondral regeneration. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res 94A: 112-121, 2010