title: Properties of cartilage engineered from elderly human chondrocytes for articular surface repair.
abstract: Numerous studies on engineering cartilage utilizing chondrocytes from juvenile animal sources have been reported. However, there are many unknown aspects of engineering cartilage using human chondrocytes-especially from middle-aged or elderly adults-which are critical for clinical application of tissue engineering in the field of orthopedic surgery. The primary aim of this study was to engineer neocartilage tissue from 50-60-year-old human chondrocytes in comparison to engineered cartilage made from juvenile swine chondrocytes (JSCs). Articular chondrocytes from middle-aged, nonarthritic humans and juvenile swine were isolated and placed in culture for expansion. The chondrocytes (passage 1) were mixed in fibrin gel at 40-60×10(6) cells/mL until polymerization. Cells/nodule constructs and devitalized cartilage-cells/hydrogel-devitalized cartilage constructs (three-layered model) were implanted into subcutaneous pockets of nude mice for 12, 18, and 24 weeks. The specimens were evaluated histologically, biochemically, and biomechanically. This allowed for direct comparison of the cartilage engineered from human versus swine cells. Histological analysis demonstrated that samples engineered utilizing chondrocytes from middle-aged adults accumulated basophilic, sulfated glycosaminoglycans (sGAG), and abundant type II collagen around the cells in a manner similar to that seen in samples engineered using JSCs at all time points. Biochemical analysis revealed that samples made with human cells had about 40%-60% of the amount hydroxyproline of native human cartilage, a trend parallel to that observed in the specimens made with swine chondrocytes. The amount of sGAG in the human chondrocyte specimens was about one-and-a-half times the amount in native human cartilage, whereas the amount in the samples made with swine chondrocytes was always less than native cartilage. The biomechanical analysis revealed that the stiffness and tensile of samples made with human cells were in a pattern similar to that seen with swine chondrocytes. This study demonstrates that chondrogenesis using articular chondrocytes from middle-aged adults can be achieved in a predictable and reliable manner similar to that shown in studies using cells from juvenile animals and can form the basis of engineering cartilage with degradable scaffolds in this patient population.
authors.affiliation: Laboratory for Musculoskeletal Tissue Engineering, Department of Orthopaedic Surgery, Massachusetts General Hospital , Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Xing
authors.initials: X
authors.lastname: Zhao
authors.forename: David A
authors.initials: DA
authors.lastname: Bichara
authors.forename: Frederick P
authors.initials: FP
authors.lastname: Ballyns
authors.forename: Jeong J
authors.initials: JJ
authors.lastname: Yoo
authors.forename: Winnie
authors.initials: W
authors.lastname: Ong
authors.forename: Mark A
authors.initials: MA
authors.lastname: Randolph
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Bonassar
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Gill
mesh_terms: D000368:Aged; D000818:Animals; D001696:Biomechanical Phenomena; D002358:Cartilage, Articular / Q000502:physiology*; D019902:Chondrocytes / Q000166:cytology*; D055119:Elastic Modulus; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D006909:Hydroxyproline / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008875:Middle Aged; D012038:Regeneration / Q000502:physiology*; D013499:Surface Properties; D034421:Sus scrofa; D013718:Tensile Strength; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry; D014945:Wound Healing
chemical_list: D006025:Glycosaminoglycans; D006909:Hydroxyproline