Evaluation of Cellular Affinity and Compatibility to Biodegradable Polyesters and Type-II Collagen-Modified Scaffolds Using Immortalized Rat Chondrocytes *Shan-hui Hsu, †Ching-Lin Tsai, and *Cheng-Ming Tang *Department of Chemical Engineering, National Chung Hsing University, Taichung; and †Department of Orthopedics, College of Medicine, National Taiwan University, Taipei, Taiwan Abstract: Immortalized rat chondrocytes (IRCs) were employed to evaluate the cytocompatibility of different biodegradable polyester scaffolds for chondrocyte seeding and cartilage tissue engineering in vitro due to the limita- tion of using freshly harvested chondroctyes. Cells were seeded onto the films and the porous substrates as well as into the three-dimensional scaffolds made of the biode- gradable polyesters including poly(L-lactide) (PLLA) and two poly(lactide-co-glycolide)s (PLGAs). The materials were characterized by water contact angle, electron spec- troscopy for chemical analysis (ESCA), and microscopy. PLGA50/50, one of the PLGAs, had the largest cell num- bers at 24 h and 96 h (close to the tissue culture polysty- rene control), possibly due to its lower contact angle, higher oxygen/carbon (O/C) atomic ratio, and larger deg- radation rate. When the surface was further modified by cross-linked Type-II collagen, cell population was signifi- cantly enhanced (two- to fourfold). The adhesion and pro- liferation behavior of IRCs on different materials was par- allel to that of rabbit chondrocytes, but was more reproducible in general. IRCs are thus suitable for eval- uation of different polymer scaffolds. Despite the favor- able cytocompatibility of PLGA50/50, blending with a small portion of PLLA is required for easy fabrication and collagen modification. Scaffolds made of blended ma- terials by freeze-drying procedure with the surface modi- fied by cross-linked Type-II collagen were demonstrated as the ideal templates for chondrocyte seeding in our study. Key Words: Biodegradable polyester scaffolds— Cartilage tissue engineering—Chondrocyte seeding— Tissue engineering. Regeneration of damaged cartilage can be stimu- lated by subchondral drilling (1), microfracturing procedures (2), periosteal or perichondral soft tissue grafting (3–6), osteochondral allografting (7,8), cell transplantation (9), growth factors (10,11), or artifi- cial matrices (12–16). The main obstacle of cartilage tissue repair was inadequate matrix production caused by limited cells, leading to formation of fi- brous tissue and the onset of degenerative joint ar- thritis. In recent years, tissue engineering techniques that involved the use of three-dimensional polymer templates or scaffolds seeded with chondrocytes, cul- tured in vitro and implanted after a certain period of time, has been an area of extensive studies (11,17,18– 21). Biodegradable materials used as scaffolding for tissue engineering fall into one of the two general categories: natural materials such as collagen (11), alginate (22), gelatin (23), and chitosan (24); or syn- thetic polymers such as polylactide, polyglycolide, and their copolymers (18,25,26). Though the former normally have better cellular attachment, the latter are more reproducible between different lots, and their microstructure and degradation rate can be ma- nipulated and controlled. A combination of the ad- vantages of both materials is the purpose of design for a new generation of biomaterials (20). A good three-dimensional scaffold should meet certain requirements including biocompatibility, bio- degradability, high porosity with pores ranging from 10–100 m, an interconnected pore network for dif- fusion of nutrients, good mechanical strength, flex- ibility, and dimensional stability (27). The prepara- tion method of a scaffold such as solvent-cast salt- leaching (25), naphthalene sublimation (28), and freeze-drying (22–24,29) could influence its biologi- Received June 2001; revised February 2002. Address correspondence and reprint requests to Dr. Ching-Lin Tsai, Department of Orthopedics, National Taiwan University Hospital, Taipei, Taiwan. E-mail: tsaicl@ha.mc.ntu.edu.tw Artificial Organs 26(7):647–658, Blackwell Publishing, Inc. © 2002 International Society for Artificial Organs 647