Effects of Scaffold Mechanical Properties On the Delivery of Stromal Cell-Derived Factor-1 From Polyurethane Scaffolds In Rat Cutaneous Wounds

Thursday, October 20, 2011: 3:55 PM
L100 E (Minneapolis Convention Center)
Elizabeth J. Adolph1, Fang Yu2, Lillian B. Nanney3, Jeffrey M. Davidson2 and Scott A. Guelcher1, (1)Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, (2)Pathology, Vanderbilt University, Nashville, TN, (3)Pathology, Cell & Developmental Biology, Vanderbilt University, Nashville, TN

In cutaneous wounds, the biochemical and mechanical environment of the defect affects the wound healing response.  Stromal cell-derived factor-1 (SDF-1) is a chemokine that has been shown to recruit mesenchymal stem cells, promote angiogenesis, and decrease inflammation in vivo.  Furthermore, mechanical forces generated in the wound site can affect myofibroblast differentiation and matrix production and organization.  In this study, we investigated the effects of SDF-1 delivered from scaffolds with varying mechanical properties in subcutaneous and excisional wounds in rats. Polyurethane (PUR) scaffolds were synthesized by reacting lysine triisocyanate with a hardener component comprising a polyester triol with a backbone composed of 60% caprolactone, 30% glycolide, and 10% lactide; triethylenediamine catalyst; water; and calcium stearate. The mechanical properties of the scaffolds were altered by varying the molecular weight of the polyester triol (450, 900, or 3000 Da), and SDF-1 was incorporated in the scaffolds as a lyophilized powder. The scaffold pore structure was analyzed using scanning electron microscopy, and the thermal transitions of the materials were evaluated by differential scanning calorimetry. Mechanical properties of the scaffolds were measured using a dynamic mechanical analyzer.  The release kinetics of SDF-1 from the scaffolds was measured in vitro by incubating samples of scaffolds containing SDF-1 in buffer, collecting the releasates and replacing release media every day, and measuring SDF-1 concentration in the releasates using an ELISA kit.  The effects of the scaffold mechanical properties and delivery of SDF-1 on wound healing were investigated using subcutaneous and excisional wound models in rats.  The study design comprises 6 treatment groups: 450 Da PUR scaffold, 900 Da PUR scaffold, 3000 Da PUR scaffold, 450 Da + SDF-1, 900 Da + SDF-1, and 3000 Da + SDF-1.  Time points include 7, 14, 21, 28, and 35 days.  The Young’s modulus is 9000 +/- 3000 kPa for the 450 Da scaffold, 270 +/- 40 kPa for the 900 Da scaffold, and 110 +/- 40 kPa for the 3000 Da scaffold.  The pore size of the scaffolds ranges from 200 – 500 μm and is not significantly affected by polyester triol molecular weight.  The in vitro release experiments show a burst release of 40% of the SDF-1 in the first 4 days followed by a sustained release that results in 50% release by day 14.  There are no substantial differences in the release profiles from the three scaffolds. Preliminary results from the rat subcutaneous wound study show that delivery of SDF-1 enhances cellular infiltration into the scaffolds and that mechanical properties of the scaffolds affect the cell and extracellular matrix organization in the wound site.

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