Insulin-like growth factor I releasing silk fibroin scaffolds induce chondrogenic differentiation of human mesenchymal stem cells

Growth factor releasing scaffolds are an emerging alternative to autologous or allogenous implants, providing a biologically active template for tissue (re)-generation. The goal of this study is to evaluate the feasibility of controlled insulin-like growth factor I (IGF-I) releasing silk fibroin (SF) scaffolds in the context of cartilage repair. The impact of manufacturing parameters (pH, methanol treatment and drug load) was correlated with IGF-I release kinetics using ELISA and potency tests. Methanol treatment induced water insolubility of SF scaffolds, allowed the control of bioactive IGF-I delivery and did not affect IGF-I potency. The cumulative drug release correlated linearly with the IGF-I load. To evaluate the chondrogenic potential of the scaffolds, hMSC were seeded on unloaded and IGF-I loaded scaffolds in TGF-β supplemented medium. Chondrogenic differentiation of hMSC was observed on IGF-I loaded scaffolds, starting after 2 weeks and more strongly after 3 weeks, whereas no chondrogenic responses were observed on unloaded control scaffolds. IGF-I loaded porous SF scaffolds have the potential to provide chondrogenic stimuli to hMSC. Evidence for in vivo cartilage (re)generation must be demonstrated by future, pre-clinical proof of concept studies.