PhD ceremony Mr. Q. Ye: Molecular and cellular mechanism of collagen degradation in the foreign body reaction
|When:||We 10-04-2013 at 11:00|
PhD ceremony: Mr. Q. Ye, 11.00 uur, Academiegebouw, Broerstraat 5, Groningen
Dissertation: Molecular and cellular mechanism of collagen degradation in the foreign body reaction
Promotor(s): prof. Y. Ren, prof. R.A. Bank
Faculty: Medical Sciences
The biopolymer collagen is often used as scaffolding biomaterial in tissue engineering. Like any other biomaterials, the implantation of collagen scaffolds induces a local inflammatory reaction known as foreign body reaction (FBR). The FBR to collagen scaffolds involves a complex cascade of spatiotemporally regulated and interconnected processes that include cellular infiltration, activation of inflammatory cells, phagocytosis and proteolysis. Ultimately this results in the resolution and degradation of the implanted scaffold. Ideally, the degradation rate should match the speed of tissue regeneration. The aim of this thesis was to search for the molecular and cellular mechanisms of degradation of collagen scaffolds in the FBR. Our data have provided several striking findings regarding the nature and regulation of the enzymatic degradation and phagocytosis of collagen scaffolds. IL-10, IL-13, TIMP-1 and DDR-2 were identified as potential therapeutic factors in the regulation of MMP-based proteolysis in the extracellular enzymatic degradation of collagen. IFN-γappears to be the optimal activator for the phagocytosis of collagen by macrophages via the up-regulation of MMP-14 and Endo180. This effect can be neutralised by the addition of IL-10. Moreover, our data have also showed that it is extremely important to choose an appropriate substrate and design the physical and chemical nature of the scaffold so that its degradation can be tuned to the rate of tissue regeneration.