The effect of IGF-I on anatomically shaped tissue-engineered menisci.
This study investigates the effect of insulin-like growth factor (IGF)-I on the development of anatomically-shaped alginate menisci seeded with meniscal fibrochondrocytes. To accomplish this, bovine meniscal fibrochondrocytes were seeded into 2% w/v alginate, crosslinked with calcium sulfate, and injected into anatomical molds derived from microcomputed tomography scans. The meniscal constructs were then cultured for up to 4 weeks with or without 100 ng/mL IGF-I supplemented in the media. Histological, immunohistological, biochemical, and mechanical analyses were performed to characterize tissue development, accumulation and localization of extracellular matrix, and mechanical properties. After 4 weeks of culture, IGF-I treatment significantly improved mechanical and biochemical properties, while maintaining DNA content, with a 26-fold increase in glycosaminoglycan (GAG) content and 10-fold increase in collagen content compared to 0-week controls, and a 3-fold increase in the equilibrium modulus at 2 weeks compared to controls. IGF-I-treated menisci had ∼60% of the GAG content of native tissue and the compressive equilibrium modulus matched native properties by 2 weeks of culture. Further, IGF-I-treated menisci developed a distinct surface layer similar to native tissue with elongated cells and collagen fibers aligned parallel to the surface, the presence of types I and II collagen, and accumulation of lubricin. This study demonstrates that IGF-I treatment can greatly increase the mechanical and biochemical properties of engineered tissues and aid in the development of a distinct surface zone similar to the superficial zone of native menisci.
Department of Biomedical Engineering, Cornell University, Ithaca, New York 14853, USA.
Jennifer L
JL
Puetzer
Bryan N
BN
Brown
Jeffrey J
JJ
Ballyns
Lawrence J
LJ
Bonassar
D000464:Alginates / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D024042:Collagen Type I / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D020723:Glucuronic Acid / Q000494:pharmacology; D006023:Glycoproteins / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D006603:Hexuronic Acids / Q000494:pharmacology; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D055595:Mechanical Phenomena / Q000187:drug effects; D008592:Menisci, Tibial / Q000033:anatomy & histology* / Q000166:cytology / Q000187:drug effects*; D023822:Tissue Engineering / Q000379:methods*; D000099158:Proteoglycan 4
D000464:Alginates; D024042:Collagen Type I; D024043:Collagen Type II; D004247:DNA; D020723:Glucuronic Acid; D006023:Glycoproteins; D006025:Glycosaminoglycans; D006603:Hexuronic Acids; D007334:Insulin-Like Growth Factor I; D000099158:Proteoglycan 4