کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5951 450 2014 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A platform technique for growth factor delivery with novel mode of action
ترجمه فارسی عنوان
یک تکنیک پلت فرم برای تحویل عامل رشد با حالت جدیدی از عمل
موضوعات مرتبط
مهندسی و علوم پایه مهندسی شیمی بیو مهندسی (مهندسی زیستی)
چکیده انگلیسی

Though growth factors allow tissue regeneration, the trade-off between their effectiveness and adverse effects limits clinical application. The key issues in current growth factor therapy largely derive from initial burst pharmacokinetics, rapid clearance, and proteolytic cleavage resulting in clinical ineffectiveness and diverse complications. While a number of studies have focused on the development of carriers, issues arising from soluble growth factor remain. In this study, we report a prodrug of growth factors constituting a novel mode of action (MoA). To mimic endogenous protein processing in cells, we developed a recombinant BMP-2 polypeptide based on a protein transduction domain (PTD) to transduce the protein into cells followed by furin-mediated protein cleavage and secretion of active growth factor. As proof of concept, a few micrograms scale of PTD-BMP-2 polypeptide sufficed to induce bone regeneration in vivo. As a simple platform, our technique can easily be extended to delivery of BMP-7 and DKK-1 as therapeutics for TGF-β and canonical Wnt signaling, respectively, to suppress the epithelial–mesenchymal transition (EMT), which constitutes a fundamental biological mechanism of many diseases. This technique largely overcomes the limitations of current soluble growth factors and opens the door to next generation growth factor therapeutics.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biomaterials - Volume 35, Issue 37, December 2014, Pages 9888–9896
نویسندگان
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