4.7 Article

Osteogenic poly(ε-caprolactone)/poloxamine homogeneous blends prepared by supercritical foaming

Journal

INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 479, Issue -, Pages 11-22

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2014.12.041

Keywords

Poly(epsilon-caprolactone)/poloxamines porous blends; Supercritical carbon dioxide-assisted foaming/mixing; Simvastatin loading/release; Cytocompatibility; Mesenchymal stem cells proliferation/differentiation; Bone fracture healing

Funding

  1. Programa Ciencia (Portugal) [PEst-C/EQB/U10102/2011, PEst-C/EQB/U10102/2013]
  2. MICINN [SAF2011-22771]
  3. Xunta de Galicia Spain [10CSA203013PR, CN2012/045]
  4. FEDER (Portugal, Spain)
  5. RIMADEL network (CYTED)
  6. Spanish Ministerio de Economia y Competitividad for the FPI grant [BES-2009-024735]

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Homogeneous poly(epsilon-caprolactone) (PCL) and poloxamines (PLXs) porous blends were prepared using a supercritical carbon dioxide-assisted foaming/mixing (SFM) approach aiming to obtain cytocompatible implantable materials presenting tunable morphologies, bioerosion rates, bioactive molecules release and osteogenic features. Pure PCL, pure PLXs (T908 and T1107 varieties) and three distinct PCL:PLX 75:25, 50:50, 25:75% w/w blends, with and without the osteogenic and angiogenic bioactive molecule simvastatin were processed at constant pressure of 20 MPa and temperature of 40 degrees C or 43 degrees C, for T1107 and T908, respectively. Obtained porous blends were characterized applying a wide range of techniques and in vitro methods. Calorimetric analysis showed that hydrophilic T908 and T1107 PLXs are miscible with PCL for all tested compositions. Prepared PCL:PLX porous blends rapidly lost mass when immersed into phosphate buffer pH 7.4 due to PLXs dissolution and then went through slow and almost constant erosion rates for the subsequent weeks due to PCL slow hydrolytic degradation, which explains the rapid initial release of simvastatin and its subsequent sustained release for longer periods of time. PCL and PCL:PLX 75:25% w/w porous blends, containing or not simvastatin, showed a high cytocompatibility with SAOS-2 cells. In addition, prepared biomaterials promoted mesenchymal stem cells proliferation and their differentiation into osteoblasts. Overall, obtained results showed novel possibilities of addressing local treatment of small bone defects/fractures using highly porous PCL:PLX homogeneous blends. (C) 2014 Elsevier B.V. All rights reserved.

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