Targeted delivery of FGF2 to subchondral bone enhanced the repair of articular cartilage defect

It is reported that growth factor (GF) is able to enhance the repair of articular cartilage (AC) defect, however underlying mechanisms of which are not fully elucidated yet. Moreover, the strategy for delivering GF needs to be optimized. The crosstalk between AC and subchondral bone (SB) play important role in the homeostasis and integrity of AC, therefore SB targeted delivery of GF represents one promising way to facilitate the repair of AC defect. In this study, we firstly investigated the effects and mechanism of FGF2 on surrounding SB and cartilage of detect defects in rabbits by using a homogenous collagen based membranes. It was found that FGF2 had a modulating effect on the defect-surrounding SB via upregulation of bone morphogenetic protein (BMP)-2, BMP4 and SOX9 at the early stage. Low dose FGF2 improved the repair upon directly injected to SB. Inhibition of BMP signaling pathway compromised the beneficial effects of FGF2, which indicated the pivotal roles of BMP in the process. To facilitate SB targeted FGF2 delivery, a double-layered inhomogeneous collagen membrane was prepared and it induced increase of BMP2 and BMP4 in the synovial fluid, and subsequent successful repair of AC defect. Taken together this targeted delivery of FGF2 to SB provides a promising strategy for AC repair owing to the relatively clear mechanism, less amount of it, and short duration of delivery. (C) 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.