Recognition of degradation-derived products from biomedical scaffolds by Toll-like receptors

The assessment of the degradation of biomaterials is an essential factor in the development of scaffolds for biomedical applications. The byproducts that are released from the scaffold in the implantation site as a result of its degradation may lead to the failure of the treatment. Their recognition by the immune cells as foreign bodies will lead to inflammation, which may result in the further release of degradative enzymes, as well as the oxidation, phagocytosis or encapsulation of the engineered-biomaterial. Toll-like receptors (TLRs) have been described to play a role in the direct recognition of scaffolds. However, their implication regarding the degradation-derived products of the latter has not been established, yet. Moreover, the impact of the chemical composition and morphology of the scaffolds on this interaction remains unknown. Herein, polycaprolactone (PCL)-hyaluronic acid (HA)-based electrospun scaffolds with randomly or aligned distributed fibers were degraded, the resulting products were collected and the recognition of the latter by TLRs was assessed by means of TLR reporter cells. Our results demonstrated that the degradation-derived products are capable of triggering TLRs, however, their triggering patterns differ from those of the original scaffolds. While scaffolds were mainly recognised by TLR 4, their degradation-derived products additionally triggered TLR 2/1. Moreover, this interaction changes over time and the alignment of the fibers appears to prevent the production of TLR triggering structures. Taken together, our findings highlight the importance of assessing the immune recognition of the degradation-derived products independently of the original scaffold.