Expression of matrix metalloproteinase-2 and -9 in exudates associated with polydimethyl siloxane and gelatin tubes implanted in mice.

Abstract

The expression of matrix metalloproteinases (MMPs), MMP-2 and -9, during the inflammatory response to two implanted biomaterials was determined. To illustrate this phenomenon, polydimethyl siloxane (PDMS), weakly crosslinked gelatin, and highly crosslinked gelatin tubes were implanted subcutaneously in mice for up to 3 weeks. Latent MMP-2 (pro-MMP-2) was seen in exudates throughout the experimental period and did not show any apparent changes in time or among the three biomaterials. The expression of MMP-9, however, showed a very different pattern. At days 4 and 8, the predominant form of MMP-9 is pro-MMP-9 (the latent form) and its level is much higher for the PDMS tube than either of the gelatin tubes. The active form of MMP-9, initially low, rose progressively over the 3-week period and reached its peak at week 2 for PDMS and highly crosslinked gelatin and at week 3 for the more degradable, weakly crosslinked gelatin. Data from the histological and cytological analysis also showed that the PDMS tube induced a much stronger cellular response than gelatin tubes, although endotoxin contamination precludes a conclusion related to biomaterial effects. We concluded that MMP-9 is a useful marker of the host inflammatory response to the implanted biomaterials and it may be useful in the assessment of biomaterial biocompatibility. Perhaps more importantly, the consequences of MMPs on matrix remodeling may become of concern in biomaterials used for tissue engineering.