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


CONCLUSIONS
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.
Rahmani-Neishaboor
Elham
E
BC Professional Fire Fighters' Burn & Wound Healing Research Lab. Jack Bell Research Center, 2660 Oak St., Vancouver, B.C. V6H 3Z6, Canada.
Jackson
John
J
Burt
Helen
H
Ghahary
Aziz
A
D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor / Q000008:administration & dosage* / Q000494:pharmacology; D048271:Chitosan; D005092:Exonucleases / Q000008:administration & dosage* / Q000494:pharmacology; D005095:Exoribonucleases; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D020100:Hydrogels; D019344:Lactic Acid; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000008:administration & dosage* / Q000494:pharmacology; D010316:Particle Size; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012867:Skin / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology
D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D020100:Hydrogels; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D048271:Chitosan; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human; D020781:Matrix Metalloproteinase 1