Composite hydrogel formulations of stratifin to control MMP-1 expression in dermal fibroblasts.

ABSTRACT

PURPOSE: Stratifin is a potent anti-fibrogenic factor that stimulates the expression of matrix metalloproteinase-1 (MMP-1) in dermal fibroblasts. The propose of this work was to develop a controlled release delivery system for stratifin that can be applied at the time of wound closure to release stratifin and stimulate the expression of MMP-1 in a sustained manner over the late stages of wound healing (after 3 days). METHODS: Stratifin was complexed to chitosan particles, which were then encapsulated in PLGA microspheres and blended into crosslinked hyaluronic acid films. In vitro release was assessed using fluorescent-tagged stratifin, cytotoxicity by MTT assay and bioactivity by measuring the levels of MMP-1 expression in cultured fibroblasts. RESULTS: The release of stratifin was delayed for 3 days and then controlled for 30 days so that 60% of the total stratifin loaded was released. The released protein significantly stimulated the expression of MMP-1 in cultured fibroblasts without compromising cell viability. By complexing to chitosan, the initial burst release was reduced, so that only 5% of stratifin was released in 3 days. CONCLUSION: This stratifin delivery system has the potential to be used as an anti-fibrogenic factor-associated wound insert for improving post-surgical scarring in closed wound.