Cartilage implants for potential in vivo use for joint repair or recon
structive surgery can be created in vitro by growing chondrocytes on b
iodegradable polymer scaffolds. Implants 1 cm in diameter by 0.176 cm
thick were made using isolated calf chondrocytes and polyglycolic acid
(PGA). By 6 weeks, the total amount of glycosaminoglycan (GAG) and co
llagen (types I and II) increased to 46% of the implant dry weight; th
ere was a corresponding decrease in the mass of PGA. Implant biochemic
al and histological compositions depended on initial cell density, sca
ffold thickness, and the methods of cell seeding and implant culture.
Implants seeded at higher initial cell densities reached higher GAG co
ntents (total and per cell), presumably due to cooperative cell-to-cel
l interactions. Thicker implants had lower GAG and collagen contents d
ue to diffusional limitations. Implants that were seeded and cultured
under mixed conditions grew to be thicker and more spatially uniform w
ith respect to the distribution of cells, matrix, and remaining polyme
r than those seeded and/or cultured statically.Implants from mixed cul
tures had a 20-40-mu m thick superficial zone of flat cells and collag
en oriented parallel to the surface and a deep zone with perpendicular
columns of cells surrounded by GAG, Mixing during cell seeding and cu
lture resulted in a more even cell distribution and enhanced nutrient
diffusion which could be related to a more favorable biomechanical env
ironment for chondrogenesis. Cartilage with appropriate form and funct
ion for in vivo implantation can thus be created by selectively stimul
ating the growth and differentiated function of chondrocytes (i.e., GA
G and collagen synthesis) through optimization of the in vitro culture
environment. (C) 1994 John Wiley & Sons, Inc.