Design and fabrication of multifunctional polymer based nanocomposites for bone tissue engineering

Abstract

Biodegradable polymer scaffolds with drug delivery function have received great research attention in bone tissue engineering due to their biocompatibility and biodegradability as temporary support systems for cell adhesion, growth, differentiation and tissue regeneration. The drug release systems of the scaffolds can deliver biologically active molecules with the desired behavior, so as to reduce the amount of drug administration and shorten the therapeutic period. Scaffolds with shape memory effects have been considered as smart materials for potential applications in minimally invasive surgery. Efforts have also been devoted to the development of composite scaffolds combining biodegradable polymers and bioactive ceramics with enhanced osteoconductive properties and mechanical strength. However, there is still no best method for three-dimensional scaffold fabrication and the influences of bioactive inclusion and porosity of the scaffold on drug delivery behavior, shape memory effect, biodegradability, bioactivity and cellular response have not yet been well addressed. The purpose of this study is to develop a technique to produce a multifunctional porous composite and investigate the influence of bioactive inclusion on its mechanical properties, biodegradability, drug release behavior, shape memory effect and cellular response for bone tissue engineering. Among the developed fabrication technologies, the solvent casting/particulate leaching method is the most commonly used scaffold fabrication method due to its simplicity, efficiency and ability to independently control the porosity and pore size of the scaffold. Nevertheless, it is limited to fabricating scaffolds with uniform pore distribution. To solve this distribution problem, a method using polymer coagulation, thermal compression molding and salt leaching has been reported however, the problem of decomposition of the active drug and polymer may be induced. In this study, a new technique has been developed to fabricate multifunctional scaffolds. This technique, called PC-DC technique, applying polymer coagulation (PC) and drug coating (DC) to solvent casting/particulate leaching method and using cold compression molding instead of conventional hot compression molding. This low temperature composite technology can contribute to a wider range of choices of drug loadings, since thermal decomposition of drug inclusion and polymer matrix can be avoided. This technique not only independently controls the pore size and porosity of the scaffolds, but also reduces solvent residual. A uniform distribution of pores throughout the polymer matrix can be achieved by this technique. Poly(ethylene glycol)/dexamethasone (PEG/Dex)-coated porous poly-D-L-lactide/nano-hydroxyapatite (PDLLA/nano-HAp) composites with homogenous pore networks and controllable porosity and pore size have been fabricated by the PC-DC technique. The compressive moduli and strengths of the composites were improved by the nano-HAp addition, which were close to those of cancellous bone. The improved wettability of the scaffold by PEG/Dex coating and nano-HAp filling was confirmed. The drug loading ability and total drug release amount of the scaffolds increased with increasing porosity level and/or the nano-HAp content. The improved bioactivity of the scaffolds was validated by the apatite formation on the scaffolds with nano-HAp addition after incubation in simulated body fluid (SBF). The compressive moduli and strengths of the scaffolds after incubation in SBF were affected by the combination of degradation, weight loss, apatite deposition and incubation time. Nano-HAp incorporation can decelerate the polymer degradation and mass loss. Moreover, the PDLLA/nano-HAp scaffolds showed a pH compensating effect to reduce the risk of chronic inflammation complications. Cyclic thermomechnical and physical shape recovery tests were firstly conducted to investigate the shape memory effect of the porous PDLLA/nano-HAp scaffolds. The results showed that desirable shape memory behavior could be achieved when the nano-HAp fracture was 10 wt%. Good biocompatibility, bioactivity and osteoconductivity of the PDLLA based samples were confirmed by investigating the ability of the scaffolds for MG63 cell adhesion, proliferation and differentiation. This study provides a new technique for the fabrication of multifunctional biodegradable drug loaded bone scaffolds with shape memory function, which is highly desirable in the bone repair applications. The findings of the study not only lead to a better understanding of the effects of nano-HAp, structure factor, surface coating on the mechanical properties, degradability, drug release behavior, shape memory effects and the cellular response of the composites in bone tissue engineering, but also provide guidelines for design and fabrication of the multifunctional composites with controllable properties for certain application requirements. A finite element model simulating the behavior of the scaffolds implanted into a human body and animal model experiments for further evaluation of the in vivo performance of the composite scaffolds are recommended for future study.