Porous Poly(3-hydroxybutyrate) Scaffolds Prepared by Non-Solvent-Induced Phase Separation for Tissue Engineering
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Article www.springer.com/13233 pISSN 1598-5032 eISSN 2092-7673
Porous Poly(3-hydroxybutyrate) Scaffolds Prepared by Non-SolventInduced Phase Separation for Tissue Engineering Jiseon Kang1 Ji-Young Hwang2 Mongyoung Huh2 Seok Il Yun*,1
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Department of Chemical Engineering and Materials Science, Sangmyung University, Seoul 03016, Korea Korea Institute of Carbon Convergence Technology, Jeonju-si, Jeonbuk 54853, Korea Received December 7, 2019 / Revised April 7, 2020 / Accepted April 8, 2020
Abstract: Highly porous poly(3-hydroxybutyrate) (PHB) scaffolds were fabricated using non-solvent-induced phase separation with chloroform as the solvent and tetrahydrofuran as the non-solvent. The microporosity, nanofiber morphology, and mechanical strength of the scaffolds were adjusted by varying the fabrication parameters, such as the polymer concentration and solvent composition. The influence of these parameters on the structure and morphology of PHB organogels and scaffolds was elucidated using small-angle neutron scattering and scanning electron microscopy. The organogels and scaffolds in this study have a complex hierarchical structure, extending over a wide range of length scales. In vitro viability assays were performed using the human keratinocyte cell line (HaCaT), and all PHB scaffolds demonstrated the excellent cell viability. Microporosity had the greatest impact on HaCaT cell proliferation on PHB scaffolds, which was determined after a 3-day incubation period with scaffolds of different morphologies and mechanical properties. The superior cell viability and the controlled scaffold properties and morphologies suggested PHB scaffolds fabricated by non-solvent-induced phase separation using chloroform and tetrahydrofuran as promising biomaterials for the applications of tissue engineering, particularly of epidermal engineering. Keywords: PHB, non-solvent-induced phase separation, scaffold, cell viability, micropores, nanofibers.
1. Introduction The phase-separation method is one of the most powerful methods used to fabricate porous scaffolds. By mixing an appropriate non-solvent into a homogeneous polymer solution, the polymer-solvent affinity decreases to induce a liquid-liquid phase separation.1-10 This forms an interpenetrating network of a polymer-rich phase and a polymer-poor phase referred to as nonsolvent-induced phase separation (NIPS). Liquid-liquid phase separation of a polymer solution can be induced, by non-solvent addition and by changing temperature. This is referred as temperature-induced phase separation (TIPS).11-26 Theoretically, a polymer-rich phase consists of the polymer and a fraction of the solvent. A polymer-poor phase contains a non-solvent and the remaining solvent. For semi-crystalline polymers, crystallization occurs in the polymer-rich phase. As a result, the solution forms a gel as microcrystallites serve as junctions for a three dimensional (3-D) network.1-4,8,24-26 The polymer-rich phase develops the skeleton of the gel monolith, whereas the polymer-poor phase flows through the ma
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