Insulin in tissue engineering of cartilage: A potential model system for growth factor application

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 mug/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 mug/ml being the most favorable concentration, The observed effects of insulin were similar to effects of IGF-I (0.05 mug/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.