Original Article
Morphology, mechanical properties, and shape memory effects of poly(lactic acid)/ thermoplastic polyurethane blend scaffolds prepared by thermally induced phase separation
Journal of Cellular Plastics 2014, Vol. 50(4) 361–379 ß The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0021955X14525959 cel.sagepub.com
Xin Jing1,2, Hao-Yang Mi1,2, Max R Salick3, Travis Cordie4, Wendy C Crone3, Xiang-Fang Peng1 and Lih-Sheng Turng2,5
Abstract Novel blended scaffolds combining biobased polylactic acid (PLA) and thermoplastic polyurethane (TPU) were fabricated by thermally induced phase separation (TIPS) using two different solvents. Pure PLA and TPU polymer scaffolds using 1,4-dioxane as the sole solvent exhibited typical ladder-like structures, while blended PLA/TPU scaffolds using the same solvent showed a more uniform microstructure. When de-ionized water was added to the solution as a non-solvent, scaffolds with the mixed solvent showed more open cells and greater interconnectivity. In compression tests, it was found that specimens, including pure PLA, TPU, and blended scaffolds with the mixed solvent, showed a higher compressive modulus than their counterparts that used dioxane as the single solvent. Dynamic mechanical analysis (DMA) was employed to characterize 1 National Engineering Research Center of Novel Equipment for Polymer Processing, South China University of Technology, Guangzhou, China 2 Wisconsin Institute for Discovery, University of Wisconsin-Madison, WI, USA 3 Department of Engineering Physics, University of Wisconsin-Madison, WI, USA 4 Department of Biomedical Engineering, University of Wisconsin-Madison, WI, USA 5 Department of Mechanical Engineering, University of Wisconsin-Madison, WI, USA
Corresponding authors: Lih-Sheng Turng, Department of Mechanical Engineering, University of Wisconsin-Madison, 1513 University Ave, Madison, WI 53706, USA. Xiang-Fang Peng, National Engineering Research Center of Novel Equipment for Polymer Processing, South China University of Technology, 381 Wushan Rd., Guangzhou 510640, China. Emails:
[email protected] (L-S Turng);
[email protected] (X-F Peng)
Downloaded from cel.sagepub.com at UNIV OF WISCONSIN-MADISON on January 8, 2016
362
Journal of Cellular Plastics 50(4)
the shape memory properties of the scaffolds. DMA indicated that the shape fixing ratio was highest in the PLA scaffolds, while the shape recovery ratio of the TPU scaffolds was the greatest among the specimens. More interestingly, when the mixed solvent was used, the shape memory property of the blended scaffolds displayed a similar deformation curve to the TPU scaffold. This was due to the presence of the TPU phase and similarity in structure between PLA/TPU and TPU scaffolds when mixed solvent was used. In the degradation test, the blended scaffolds showed a balanced degradation behavior in-between the more easily degraded PLA and the more stable TPU in the phosphate-buffered saline (PBS), and the addition of water to the systems accelerated the degradation process of the specimens. Cell culture results showed that all of the scaffolds had good biocompatibility. Keywords Thermoplastic polyurethane (TPU), polylactic acid (PLA), thermally induced phase separation (TIPS), shape memory effect, biocompatibility
Introduction Three-dimensional polymeric scaffolds are critical in tissue engineering as they are the foundation for cell attachment, proliferation, differentiation, and eventual tissue formation.1–3 The overall goal when fabricating a tissue engineered scaffold is to mimic the native extracellular matrix (ECM) of the tissue of interest, which is naturally a very porous material. Porosity plays a significant role in creating the proper environment for cells to proliferate. Ideally the scaffold should have pores that are open, interconnected, hierarchical in size, and have a uniform distribution throughout the scaffold, all while maintaining the required mechanical properties.4 Open interconnected pores will allow cells to infiltrate the scaffold material and also allow for the mass transport of cell nutrients and waste. Hierarchical effect refers to variable pore sizes on different scales; macrosized pores (>50 mm) will influence tissue shape, microsized pores (1–50 mm) will influence cell function, and nanosized pores (1–1000 nm) will influence nutrient diffusion.5 A great variety of approaches have been developed to fabricate porous scaffolds such as electrospinning,6–13 porogen leaching,14–21 and gas foaming,22–24 just to mention a few. Researchers are also beginning to combine different methods together to fabricate highly porous and interconnected scaffolds. Thermally induced phase separation (TIPS) is a versatile technique used to produce porous scaffolds. In TIPS, a homogeneous solution of polymer–solvent or polymer–solvent–non-solvent is quenched to a lower temperature to induce the uniform solution into polymer-rich and polymer-lean phases. After evacuation, extraction, and sublimation of the solvent, pores are formed in the scaffolds. There are two
Downloaded from cel.sagepub.com at UNIV OF WISCONSIN-MADISON on January 8, 2016
Jing et al.
363
mechanisms of phase separation. (1) Solid–liquid phase separation is where the solvent forms crystals at the lower temperature before the phase separation between the solvent and polymer occurs. The sublimation of the solvent will give rise to the ladder-like porous structure in the scaffold.25 (2) Liquid–liquid phase separation, on the other hand, generates polymer-rich and polymer-lean liquid phases. The further development of polymer-lean phases in the spinodal phase separation creates a highly interconnected porous structure in the scaffolds.26 The TIPS process is more attractive over other approaches due to its ability to form an intrinsically interconnected polymer network in one simple process. By manipulating the processing parameters and system compositions, it is a very convenient method for fabricating suitable tissue engineering scaffolds. Varied scaffolds with different morphologies have been investigated using this technique, such as aligned porous structures,27 honeycomb monolith structures,28 beady/stringy, ladder-like and tube-like structures,29 and porous nanofibrous polymer scaffolds.30 Polymer scaffolds with varied compositions have also been prepared using the TIPS technique, such as poly("-caprolactone) (PCL) scaffolds modified by hydroxyapatite (HA),31 polylactide–co-glycolide (PLGA),26,32,33 poly (hydroxyabutyrate-co-hydroxyvalerate)/hydroxyapatite (PHBV/HA) polymer composite scaffolds,34 polyurethane scaffolds,35 and PLLA–PCL blend porous membranes.36 Thermoplastic polyurethane (TPU), which is comprised of soft and hard segments, is a biocompatible elastomer. With the different ratios of soft to hard segments, TPU can exhibit a broad range of mechanical properties over a wide temperature range. Due to its excellent physical properties and biocompatibility, TPU has been widely used as a biomaterial for applications such as blood vessels,37 catheters,38,39 cartilage,40 and so on. Biodegradable polylactic acid (PLA) exhibits little to no elastic behavior and is not favored for applications requiring high flexibility or deformation in situ. The PLA/TPU blended matrix, which is a combination of soft material TPU and rigid material PLA, is expected to act as an artificial ECM by possessing suitable mechanical strength and flexibility in between the TPU and PLA. However, there is little research into PLA/TPU foamed scaffolds prepared by TIPS. In this paper, two different kinds of solvents, pristine 1,4-dioxane and dioxane/water, were employed to dissolve PLA/TPU blends with different compositions to produce scaffolds that may be suitable for tissue engineering applications.
Materials and methods Materials PLA, 8052D, was purchased from Natureworks, LLC. Medical grade TPU (TexinÕ Rx85A) was generously donated by Bayer Material Science Inc. 1,4Dioxane was bought from Sigma-Aldrich (USA). Water was ultra-pure grade (
