title: Localized controlled release of stratifin reduces implantation-induced dermal fibrosis.
abstract: Localized controlled release of anti-fibrogenic factors can potentially prevent tissue fibrosis surrounding biomedical prostheses, such as vascular stents and breast implants. We have previously demonstrated that therapeutic intervention with topically applied stratifin in a rabbit ear fibrotic model not only prevents dermal fibrosis but also promotes more normal tissue repair by regulating extracellular matrix deposition. In this work, the anti-fibrogenic effect of a controlled release form of stratifin was investigated in the prevention of fibrosis induced by dermal poly(lactic-co-glycolic acid) (PLGA) microsphere/poly(vinyl alcohol) (PVA) hydrogel implants. Pharmacodynamic effects were evaluated by histopathological examination of subcutaneous tissue surrounding implanted composites. Controlled release of stratifin from PLGA microsphere/PVA hydrogel implants significantly moderated dermal fibrosis and inflammation by reducing collagen deposition (30%), total tissue cellularity (48%) and infiltrated CD3(+) immune cells (81%) in the surrounding tissue compared with the stratifin-free implants. The controlled release of stratifin from implants markedly increased the level of matrix metalloproteinase-1 expression in the surrounding tissue, which resulted in less collagen deposition. These stratifin-eluting PLGA/PVA composites show promise as coatings to decrease the typical fibrosis exhibited around implanted biomedical prostheses, such as breast implants and vascular stents.
authors: Burn and Wound Healing Research Laboratory, Department of Surgery, University of British Columbia, Vancouver, BC, Canada.
authors: Elham
authors: E
authors: Rahmani-Neishaboor
authors: Ryan
authors: R
authors: Hartwell
authors: Reza
authors: R
authors: Jalili
authors: John
authors: J
authors: Jackson
authors: Erin
authors: E
authors: Brown
authors: Aziz
authors: A
authors: Ghahary
mesh_terms: D048948:14-3-3 Proteins / Q000494:pharmacology*; D000818:Animals; D014408:Biomarkers, Tumor / Q000494:pharmacology*; D017252:CD3 Complex / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D003692:Delayed-Action Preparations; D020405:Dermis / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology*; D004817:Epidermis / Q000187:drug effects / Q000473:pathology; D005092:Exonucleases / Q000494:pharmacology*; D005095:Exoribonucleases; D005355:Fibrosis; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D006801:Humans; D020007:Implants, Experimental / Q000009:adverse effects; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D019919:Prosthesis Implantation / Q000009:adverse effects*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D017252:CD3 Complex; D003692:Delayed-Action Preparations; D003094:Collagen; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human; D020781:Matrix Metalloproteinase 1; D016650:Fluorescein-5-isothiocyanate