title: BMP-7 loaded microspheres as a new delivery system for the cultivation of human chondrocytes in a collagen type-I gel.
abstract: In recent years, interest in chondrocyte cultures for transplantation has gained increasing attention. We investigated the use of PGLA microspheres as a new delivery system for BMP-7 and the effects on human chondrocytes cultivated in a 3D collagen gel culture. In an in vitro study, human chondrocytes obtained from osteoarthritic knee joints were released, transferred into a collagen type-I gel, and cultivated up to 14 days. In the treatment group PGLA microspheres loaded with human recombinant BMP-7 protein were added to the matrix. After the cultivation period, histological and immunohistochemical investigations were performed. In addition, the aggrecan core protein and type-II collagen mRNA concentrations were measured by real-time PCR. Histological staining for proteoglycan and collagen type-II protein and quantification via digital image processing revealed a significantly higher content in the samples cultivated with BMP-7 loaded microspheres in comparison to the control samples. Moreover, the collagen gel scaffold was partially remodeled by the chondrocytes and replaced by newly synthesized extracellular matrix. Cellular proliferation as well as apoptosis were low. In conclusion, we consider the PGLA microsphere system to be a functional device for the delivery of growth factors during the cultivation of articular chondrocytes leading to an increased content of type-II collagen and proteoglycan in the extracellular matrix.
authors.affiliation: Department of Orthopedics, Aachen University Hospital, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Gavénis
authors.forename: Doris
authors.initials: D
authors.lastname: Klee
authors.forename: Rui M
authors.initials: RM
authors.lastname: Pereira-Paz
authors.forename: Matthias
authors.initials: M
authors.lastname: von Walter
authors.forename: Jürgen
authors.initials: J
authors.lastname: Mollenhauer
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schneider
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schmidt-Rohlfing
mesh_terms: D000368:Aged; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D019902:Chondrocytes / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects*; D024042:Collagen Type I / Q000737:chemistry / Q000378:metabolism; D024043:Collagen Type II / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D005109:Extracellular Matrix; D005260:Female; D005782:Gels; D006801:Humans; D008297:Male; D008863:Microspheres; D011509:Proteoglycans / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D023181:Antimicrobial Cationic Peptides; C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D024042:Collagen Type I; D024043:Collagen Type II; D005782:Gels; D011509:Proteoglycans; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C045866:peptide-Gly-Leu-amide