title: Maturation of tissue engineered cartilage implanted in injured and osteoarthritic human knees.
abstract: The regeneration of damaged organs requires that engineered tissues mature when implanted at sites of injury or disease. We have used new analytic techniques to determine the extent of tissue regeneration after treatment of knee injury patients with a novel cartilage tissue engineering therapy and the effect of pre-existing osteoarthritis on the regeneration process. We treated 23 patients, with a mean age of 35.6 years, presenting with knee articular cartilage defects 1.5 cm2 to 11.25 cm2 (mean, 5.0 cm2) in area. Nine of the patients had X-ray evidence of osteoarthritis. Chondrocytes were isolated from healthy cartilage removed at arthroscopy. The cells were cultured for 14 days, seeded onto esterified hyaluronic acid scaffolds (Hyalograft C), and grown for a further 14 days before implantation. A second-look biopsy was taken from each patient after 6 to 30 months (mean, 16 months). After standard histological analysis, uncut tissue was further analyzed using a newly developed biochemical protocol involving digestion with trypsin and specific, quantitative assays for type II collagen, type I collagen, and proteoglycan, as well as mature and immature collagen crosslinks. Cartilage regeneration was observed as early as 11 months after implantation and in 10 out of 23 patients. Tissue regeneration was found even when implants were placed in joints that had already progressed to osteoarthrosis. Cartilage injuries can be effectively repaired using tissue engineering, and osteoarthritis does not inhibit the regeneration process.
authors.affiliation: University of Bristol Academic Rheumatology, Department of Clinical Science at North Bristol, Avon Orthopaedic Centre, Southmead Hospital, Bristol, United Kingdom.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Hollander
authors.forename: Sally C
authors.initials: SC
authors.lastname: Dickinson
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Sims
authors.forename: Paola
authors.initials: P
authors.lastname: Brun
authors.forename: Roberta
authors.initials: R
authors.lastname: Cortivo
authors.forename: Elisaveta
authors.initials: E
authors.lastname: Kon
authors.forename: Maurilio
authors.initials: M
authors.lastname: Marcacci
authors.forename: Stefano
authors.initials: S
authors.lastname: Zanasi
authors.forename: Anna
authors.initials: A
authors.lastname: Borrione
authors.forename: Claudio
authors.initials: C
authors.lastname: De Luca
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pavesio
authors.forename: Carlo
authors.initials: C
authors.lastname: Soranzo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Abatangelo
mesh_terms: D000293:Adolescent; D000328:Adult; D001705:Bioprosthesis; D002356:Cartilage / Q000378:metabolism / Q000637:transplantation*; D019902:Chondrocytes / Q000378:metabolism / Q000637:transplantation*; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000628:therapy*; D012038:Regeneration; D013997:Time Factors; D023822:Tissue Engineering
chemical_list: D016326:Extracellular Matrix Proteins; D006820:Hyaluronic Acid