The long-term objective of this project is to develop tissue-engineered cartilage for human therapy using a novel degradable poly(ethylene glycol) hydrogel. We hypothesize that a semi-interpenetrating polymer network composed of poly(ethylene glycol) dimethacrylate and poly(ethylene oxide) (MW<2OkDa) can provide a temporary biocompatible matrix for the production of tissue-engineered cartilage with uniform cell content and distribution and biochemical and biomechanical properties approaching normal cartilage. We will optimize the hydrogel formulation as evaluated by matrix content and compressive properties using articular and septal chondrocytes to determine the best combination of parameters to produce tissue-engineered cartilage. We will demonstrate the ability to grow thicker pieces of cartilage (>2 mm) molded to shapes specific for craniofacial or orthopaedic applications. Use of biodegradable, biocompatible hydrogels has many advantages over mesh polymer scaffolds. Hydrogel can be molded to specific shapes, supports cell growth and matrix deposition in constructs thicker than 2 mm, may serve to hide potentially immunogenic chondrocytes enabling development of off the shelf allogeneic products, and is useful for growing autologous cartilage where donor cells are limited. Based on the biomechanical properties exhibited by the optimal hydrogel formulation determined in Phase I, we will develop cartilage for either rhinoplasty or for orthopaedic defect repair. PROPOSED COMMERCIAL APPLICATION: Cartilage-related orthopaedic (400,000 procedures in 1996) and craniofacial (300,000 procedures in 1996) surgeons annually treat 700,000 patients in the United States alone. If left untreated, these defects can lead to progressive degeneration of the cartilage resulting in impaired function, increased pain and/or disfigurement. The motivation for developing tissue-engineered cartilage comes from an increasing clinical need for graft material of appropriate shapes, sizes, and biomechanical properties to effectively repair damaged or missing cartilage.
