Effects of growth-factor-enhanced culture on a chondrocyte-collagen implant for cartilage repair.
The effects of incubation and addition of growth factors to a chondrocyte-seeded collagen implant for cartilage repair were studied. Type I collagen matrices seeded with lapine articular chondrocytes and unseeded controls cultured in the presence and absence of fibroblast growth factor and insulin for 2, 6, and 9 weeks were subjected to biomechanical, biochemical, and histological analysis. Aggregate modulus of elasticity of seeded implants decreased by half at 6 weeks, then rose by a factor of 10 above initial values. Permeability of seeded implants and their controls decreased steadily. Glycosaminoglycan content peaked at 6 weeks, coinciding with the greatest number of chondrocytes and mitotic activity in seeded implants. Chondrocytes remained phenotypically stable and metabolically active; they incorporated glycosaminoglycan into the extracellular matrix, and formed an organized pericellular environment despite the predicted resorption of the collagen matrix. Adding fibroblast growth factor and insulin tripled the rate of cell turnover and doubled the glycosaminoglycan content of seeded implants, but had no effect on their material properties. In vitro incubation for 6 weeks in the presence of fibroblast growth factor and insulin creates a metabolically and mitotically active chondrocyte-collagen composite for implantation into articular cartilage defects.
Toolan
B C
BC
Department of Bioengineering, Hospital for Joint Diseases Orthopaedic Institute, New York, New York 10003, USA.
Frenkel
S R
SR
Pachence
J M
JM
Yalowitz
L
L
Alexander
H
H
D000704:Analysis of Variance; D000818:Animals; D001705:Bioprosthesis; D002358:Cartilage, Articular / Q000166:cytology* / Q000293:injuries*; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D003094:Collagen; D004247:DNA / Q000032:analysis; D004548:Elasticity; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D006025:Glycosaminoglycans / Q000032:analysis / Q000096:biosynthesis; D006133:Growth Substances / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D010539:Permeability; D011817:Rabbits; D013314:Stress, Mechanical; D013710:Tendons; D013997:Time Factors
D006025:Glycosaminoglycans; D006133:Growth Substances; D007328:Insulin; D005346:Fibroblast Growth Factors; D003094:Collagen; D004247:DNA