Development of layered porous poly(l-lactide) for bone regeneration

Abstract

Biodegradable porous materials called scaffold have been used for cell culture in tissue engineering. Poly(L-lactide) (PLLA) and poly(e-caprolactone) (PCL), typical biodegradable polymers, have been considered as the candidates for polymeric scaffolds [1–7]. These scaffolds should have proper mechanical properties comparative to target tissues to be regenerated. For example, scaffolds for bone tissue may need to have much higher mechanical properties than for softer tissues. However, such polymeric scaffolds have much lower mechanical properties than bone tissue, and may easily be collapsed when implanted into damaged part of bone tissue. In this study, therefore, layered structure was introduced to improve the mechanical properties of porous PLLA scaffold. In this newly developed structure, a porous core region is surrounded by a solid layer that works as load bearing structure. This kind of layered structure is very similar to the bone structure in which porous cancellous bone is surrounded by cortical bone. Porous structure of PLLA was fabricated by the solid– liquid phase separation and freeze-drying methods [6, 8]. In the first process, PLLA pellets were dissolved in 1,4-dioxane to make 3 and 7 wt% solutions. These solutions were then filled into a test tube in which a PLLA film with a thickness of 250 lm was inserted. The PLLA dioxane solutions in test tubes were cooled from the bottom surfaces at a constant rate by using liquid nitrogen to induce solid–liquid phase separation. The phase-separated samples were then dried under vacuum at -5 C for about 1 week to remove the solvent completely. Cylindrical samples were obtained and then trimmed to be a cylinder with 8.5 mm diameter and 11 mm length. For each of the samples, the diameter and length were measured at three different positions and averaged values were then used to estimate the volume of the cylinder. The density of the sample was evaluated from the volume and weight. Porosity (volume fraction of pores) of the scaffold was then estimated from the densities of PLLA solid and the scaffold. Compression tests of the scaffolds were performed using a conventional mechanical testing machine at a loading rate of 1 mm/min. Five specimens were tested for each of the samples. Elastic moduli were then estimated from the initial slope of the stress–strain curves. Compressive strength values were also evaluated at the critical points where the stress–strain curves reached the first inflection points that corresponded to the end of elastic deformation behavior. A field-emission scanning electron microscope (FE-SEM) was also used to observe the microstructures of the porous samples and the deformation behavior of the porous samples at the critical point. FE-SEM microphotographs of the monoand layeredstructural scaffolds made from 3 wt% solution are shown in Fig. 1. The mono-structure shows homogeneous distribution of pores with larger holes that are produced by solvent exhaust. It is seen that the solid layer is firmly connected to the porous core region. For the 3 wt% scaffolds, the range of pore size is about 10–100 lm, and for the 7 wt%, the range is 10–55lm. The size of solvent exhaust hole is 90–120 lm. The porosity values of the scaffolds are shown in Fig. 2. The porosities tend to decrease with increase of PLLA concentration. The porosities of both mono-scaffolds are much higher than J.-E. Park Interdisciprinary Graduate School of Engineering and Sciences, Kyushu University, 6-1 Kasuga-koen, Kasuga 816-8580, Japan