title: Engineering human cell-based, functionally integrated osteochondral grafts by biological bonding of engineered cartilage tissues to bony scaffolds.
abstract: In this study, we aimed at developing and validating a technique for the engineering of osteochondral grafts based on the biological bonding of a chondral layer with a bony scaffold by cell-laid extracellular matrix. Osteochondral composites were generated by combining collagen-based matrices (Chondro-Gide) containing human chondrocytes with devitalized spongiosa cylinders (Tutobone) using a fibrin gel (Tisseel). We demonstrate that separate pre-culture of the chondral layer for 3 days prior to the generation of the composite allows for (i) more efficient cartilaginous matrix accumulation than no pre-culture, as assessed histologically and biochemically, and (ii) superior biological bonding to the bony scaffold than 14 days of pre-culture, as assessed using a peel-off mechanical test, developed to measure integration of bilayered materials. The presence of the bony scaffold induced an upregulation in the infiltrated cells of the osteoblast-related gene bone sialoprotein, indicative of the establishment of a gradient of cell phenotypes, but did not affect per se the quality of the cartilaginous matrix in the chondral layer. The described strategy to generate osteochondral plugs is simple to be implemented and--since it is based on clinically compliant cells and materials--is amenable to be readily tested in the clinic.
authors.affiliation: Department of Surgery, University Hospital Basel, Basel, Switzerland.
authors.forename: Celeste
authors.initials: C
authors.lastname: Scotti
authors.forename: Dieter
authors.initials: D
authors.lastname: Wirz
authors.forename: Francine
authors.initials: F
authors.lastname: Wolf
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Schaefer
authors.forename: Vivienne
authors.initials: V
authors.lastname: Bürgin
authors.forename: Alma U
authors.initials: AU
authors.lastname: Daniels
authors.forename: Victor
authors.initials: V
authors.lastname: Valderrabano
authors.forename: Christian
authors.initials: C
authors.lastname: Candrian
authors.forename: Marcel
authors.initials: M
authors.lastname: Jakob
authors.forename: Ivan
authors.initials: I
authors.lastname: Martin
authors.forename: Andrea
authors.initials: A
authors.lastname: Barbero
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism; D018929:Cell Culture Techniques / Q000379:methods; D002478:Cells, Cultured; D018920:Coculture Techniques; D024043:Collagen Type II / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008422:Materials Testing; D008875:Middle Aged; D016348:Osseointegration; D015203:Reproducibility of Results; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D019737:Transplants
chemical_list: D024043:Collagen Type II