title: Simultaneous anabolic and catabolic responses of human chondrocytes seeded in collagen hydrogels to long-term continuous dynamic compression.
abstract: Cartilage repair strategies increasingly focus on the in vitro development of cartilaginous tissues that mimic the biological and mechanical properties of native articular cartilage. However, current approaches still face problems in the reproducible and standardized generation of cartilaginous tissues that are both biomechanically adequate for joint integration and biochemically rich in extracellular matrix constituents. In this regard, the present study investigated whether long-term continuous compressive loading would enhance the mechanical and biological properties of such tissues. Human chondrocytes were harvested from 8 knee joints (n=8) of patients having undergone total knee replacement and seeded into a collagen type I hydrogel at low density of 2×10(5)cells/ml gel. Cell-seeded hydrogels were cut to disks and subjected to mechanical stimulation for 28 days with 10% continuous cyclic compressive loading at a frequency of 0.3 Hz. Histological and histomorphometric evaluation revealed long-term mechanical stimulation to significantly increase collagen type II and proteoglycan staining homogenously throughout the samples as compared to unstimulated controls. Gene expression analyses revealed a significant increase in collagen type II, collagen type I and MMP-13 gene expression under stimulation conditions, while aggrecan gene expression was decreased and no significant changes were observed in the collagen type II/collagen type I mRNA ratio. Mechanical propertywise, the average value of elastic stiffness increased in the stimulated samples. In conclusion, long-term mechanical preconditioning of human chondrocytes seeded in collagen type I hydrogels considerably improves biological and biomechanical properties of the constructs, corroborating the clinical potential of mechanical stimulation in matrix-associated autologous chondrocyte transplantation (MACT) procedures.
authors.affiliation: Department of Orthopaedic Surgery, Aachen University Hospital, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Nebelung
authors.forename: Karsten
authors.initials: K
authors.lastname: Gavenis
authors.forename: Christian
authors.initials: C
authors.lastname: Lüring
authors.forename: Bei
authors.initials: B
authors.lastname: Zhou
authors.forename: Ralf
authors.initials: R
authors.lastname: Mueller-Rath
authors.forename: Marcus
authors.initials: M
authors.lastname: Stoffel
authors.forename: Markus
authors.initials: M
authors.lastname: Tingart
authors.forename: Björn
authors.initials: B
authors.lastname: Rath
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D019902:Chondrocytes / Q000502:physiology*; D024042:Collagen Type I / Q000737:chemistry*; D019245:Compressive Strength / Q000502:physiology; D055119:Elastic Modulus / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D008297:Male; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008875:Middle Aged; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
chemical_list: D024042:Collagen Type I; D016326:Extracellular Matrix Proteins; D020100:Hydrogels