Novel porous scaffolds of poly(lactic acid) produced by phase-separation using room temperature ionic liquid and the assessments of biocompatibility |
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Authors: | Hye-Young Lee Guang-Zhen Jin Ueon Sang Shin Joong-Hyun Kim Hae-Won Kim |
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Affiliation: | (1) Biomaterials & Tissue Engineering Laboratory, Department of Nanobiomedical Science & WCU Research Center, Dankook University, Cheonan, South Korea;(2) Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, South Korea;(3) Department of Biomaterials Science, School of Dentistry, Dankook University, Cheonan, South Korea; |
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Abstract: | Here we prepared three-dimensional (3D) porous-structured biodegradable polymer scaffolds for tissue regeneration using room
temperature ionic liquids (RTILs) as a novel porogen, and addressed their biological properties, including in vitro cell growth
and differentiation and in vivo tissue compatibility. RTIL based on 1-butyl-3-methylimidazolium (bmim]) bearing hydrophilic
anion Cl was introduced within the polymer structure to provide a pore network. A mixture of poly(lactic acid) (PLA) with
RTIL dissolved in an organic solvent formed a bi-continuous network during the drying process. Selective dissolution of the
RTIL phase was facilitated in ethanol, which resulted in a porous network of the polymer phase with complete removal of the
RTIL. The RTILs-assisted porous scaffolds showed a typical open-channeled network with pore sizes over 100 μm and porosities
of about 86–94%. For the biocompatibility assessments of the scaffolds, mesenchymal stem cells (MSCs) derived from rat bone
marrow were seeded onto the PLA scaffold, and the cell proliferation and osteoblastic differentiation behaviors were examined.
Results showed a typical on-going increase in the cell population with a level comparable to that observed on the tissue culture
plastic control, indicating good cell compatibility. When cultured in an osteogenic medium, the alkaline phosphatase (ALP)
activity of the cells on the PLA scaffolds was stimulated to increase with time from 7 to 14 days, in a similar manner to
that on the control. Moreover, the expression of genes related to osteoblasts, including collagen type I, osteocalcin and
bone sialoprotein, was stimulated on the 3D PLA scaffold during culture for up to 14 days, with levels higher than those on
the control, suggesting the developed scaffold provided a 3D matrix condition for osteogenesis. An in vivo pilot study conducted
subcutaneously in rat for 4 weeks revealed good tissue compatibility of the scaffold, with the ingrowth of cells and formation
of collageneous tissue around and deep within the pores of the scaffold and no significant inflammatory reaction. Taken together,
this novel method of using RTILs as a pore generator is considered to be useful in the development of biocompatible porous
polymer scaffolds for tissue regeneration. |
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