title: Insulin in tissue engineering of cartilage: a potential model system for growth factor application.
abstract: Investigation of novel experimental application systems for growth factors or other bioactive substances in tissue engineering is often limited by high costs of substances and would benefit from a defined and easily controllable model tissue system. Herein, we demonstrate a potential three-dimensional in vitro system using engineered cartilage as a model tissue and readily available insulin as a model drug. Previously it has been shown that insulin-like growth factor-I (IGF-I) has profound effects on tissue-engineered cartilage in vitro. Insulin is known to bind to the IGF-I receptor and to elicit significant responses in cartilage. In this study, bovine articular chondrocytes were seeded onto biodegradable polyglycolic acid (PGA) scaffolds and cultured for up to 7 weeks. Exogenous insulin (0.05-50 microg/ml) increased the growth rate and the glycosaminoglycan fraction of tissue-engineered cartilage, decreased the cell number in the tissue constructs, and improved the morphological appearance, with 2.5 microg/ml being the most favorable concentration. The observed effects of insulin were similar to effects of IGF-I (0.05 microg/ml) and were in agreement with the reported binding constants of IGF-I and insulin at the IGF-I receptor. Besides the possibility to employ insulin as a potent substance to improve tissue-engineered cartilage, the presented easily controllable in vitro system may be used in the future to evaluate experimental growth factor application devices using economically favorable insulin as a model protein.
authors.affiliation: Department of Pharmaceutical Technology, University of Regensburg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Kellner
authors.forename: M B
authors.initials: MB
authors.lastname: Schulz
authors.forename: A
authors.initials: A
authors.lastname: Göpferich
authors.forename: T
authors.initials: T
authors.lastname: Blunk
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D002356:Cartilage / Q000187:drug effects* / Q000254:growth & development; D002417:Cattle; D018929:Cell Culture Techniques / Q000379:methods; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects; D006133:Growth Substances / Q000008:administration & dosage* / Q000494:pharmacology*; D007328:Insulin / Q000008:administration & dosage* / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000494:pharmacology; D008954:Models, Biological; D011108:Polymers / Q000737:chemistry; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D001672:Biocompatible Materials; D006133:Growth Substances; D007328:Insulin; D011108:Polymers; D007334:Insulin-Like Growth Factor I