Thermoreversible hydrogel scaffolds for articular cartilage engineering John P. Fisher, 1 * Seongbong Jo, 2 Antonios G. Mikos, 2 A. Hari Reddi 1 1 Department of Orthopaedic Surgery, Center for Tissue Regeneration and Repair, School of Medicine, University of California, Davis, Research Building I, Room 2000, 4635 Second Avenue, Sacramento, California 95817 2 Department of Bioengineering, Rice University, P.O. Box 1892, MS 142, Houston, Texas 77251 Received 18 December 2003; revised 18 June 2004; accepted 22 June 2004 Published online 14 September 2004 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jbm.a.30148 Abstract: Articular cartilage has limited potential for re- pair. Current clinical treatments for articular cartilage dam- age often result in fibrocartilage and are associated with joint pain and stiffness. To address these concerns, researchers have turned to the engineering of cartilage grafts. Tissue engineering, an emerging field for the functional restoration of articular cartilage and other tissues, is based on the utili- zation of morphogens, scaffolds, and responding progeni- tor/stem cells. Because articular cartilage is a water-laden tissue and contains within its matrix hydrophilic proteogly- cans, an engineered cartilage graft may be based on syn- thetic hydrogels to mimic these properties. To this end, we have developed a polymer system based on the hydrophilic copolymer poly(propylene fumarate-co-ethylene glycol) [P(PF-co-EG)]. Solutions of this polymer are liquid below 25°C and gel above 35°C, allowing an aqueous solution containing cells at room temperature to form a hydrogel with encapsulated cells at physiological body temperature. The objective of this work was to determine the effects of the hydrogel components on the phenotype of encapsulated chondrocytes. Bovine articular chondrocytes were used as an experimental model. Results demonstrated that the com- ponents required for hydrogel fabrication did not signifi- cantly reduce the proteoglycan synthesis of chondrocytes, a phenotypic marker of chondrocyte function. In addition, chondrocyte viability, proteoglycan synthesis, and type II collagen synthesis within P(PF-co-EG) hydrogels were inves- tigated. The addition of bone morphogenetic protein-7 in- creased chondrocyte proliferation with the P(PF-co-EG) hy- drogels, but did not increase proteoglycan synthesis by the chondrocytes. These results indicate that the temperature- responsive P(PF-co-EG) hydrogels are suitable for chondro- cyte delivery for articular cartilage repair. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 71A: 268 –274, 2004 Key words: cartilage; chondrocytes; morphogens; hydro- gels; tissue engineering INTRODUCTION Native articular cartilage is a durable long-lasting tissue, with an extracellular matrix consisting mostly of proteoglycans and type II collagen. Cartilage matrix proteoglycans, most notably aggrecan, are negatively charged molecules that induce both a repelling force, due to charged proteoglycans repulsion of negatively, and an osmotic swelling force, as water moves into the tissue to ensure electroneutrality. 1 The resulting stress that is induced in articular cartilage allows the tissue to withstand large loads by virtue of the matrix’s tensile strength and the exudable water held within the tissue. As a result, articular cartilage possesses significant mechanical properties, with a compressive modulus of 0.79 MPa, a shear modulus of 0.69 MPa, and a tensile modulus varying between 0.3 and 10.2 MPa. 2 Nevertheless, mechanical loads may be applied to articulating joints with such great magnitude and swift rate, that cartilage is not able to accept the force and thus fails by either surface or both surface and subchondral bone disruption. The surgical options for articular cartilage repair typically include graft implantation and subchondral bone microfractures. Grafting procedures entail the implantation of autologous osteochondral plugs, allo- grafts, periosteal grafts, and perichondrial grafts. 3 Subchondral bone penetration procedures include subchondral drilling, microfracture, and spongializa- tion. Thus, although both procedures rely on growth factors, differentiated cells, and pluripotent mesen- chymal cells to repair the damaged site, the grafting *Present address: Department of Chemical Engineering, University of Maryland, College Park, MD 20742 Correspondence to: A. H. Reddi; e-mail: ahreddi@ucdavis. edu Contract grant sponsor: Lawrence Ellison Chair Endow- ment for Musculoskeletal Molecular Biology and Regenera- tive Medicine Contract grant sponsor: National Institutes of Health; con- tract grant number: R01-AR48756 © 2004 Wiley Periodicals, Inc.