Development of highly porous polylactic acid-based monoliths containing sol-gel-derived 45S5 Bioglass®

It has been shown that highly porous composite scaffolds consisting of biodegradable polymeric matrices and well-dispersed bioactive glass nanoparticles have a great potential for creating the ideal scaffold for tissue engineering purposes. In spite of this, the scaffold with ideal morphology, degradation rate and mechanical properties has not yet been developed. In the first stage of this study, the most bioactive glass composition, 45S5 Bioglass® (45% SiO2, 24.5% CaO, 24.5% Na2O and 6% P2O5 (wt.%)), was synthesized by a straightforward, nitrate-free sol-gel method. This route allowed for the production of a fully amorphous product with an appropriately high specific surface area (11.75 m2/g), which is expected to have an excellent bioactivity for bone regeneration applications. In the second stage, a fundamental study was performed on the PLA – dichloromethane (solvent) – hexane (nonsolvent) ternary system which was essential for the subsequent production of porous PLA monoliths from this system. The ternary phase diagram of this system was experimentally developed at room conditions in order to identify the liquid-liquid phase separated region. The phase separation kinetics were also studied using turbidity measurements, showing that a small increase in PLA content can significantly increase the phase separation rate of the system. The third stage of this study involved the fabrication of PLA foams using a solvent-based foaming process: nonsolvent induced phase separation (NIPS), which is a template-free and a very versatile technique. For this purpose, systems from the liquid-liquid phase separated region were selected and allowed to phase separate at various temperatures and then gel. Shrinkage of the gels during drying was monitored in order to identify compositions with minimum shrinkage and highest porosity. This method was able to produce semi-crystalline PLA foams with high specific surface area (up to 54.14 m2/g), high porosity (up to 90.8%) and compressive modulus ranging from 1.8 to 57 MPa. Crystallization during phase separation and the phase separation mechanisms were explained and discussed for various compositions and conditions. Depending on the ternary composition and the phase separation standing temperature, mesoporous and combined meso/macroporous morphologies were produced. The latter morphology is very promising for bone scaffold applications since the macropores are vital for vascularization and bone ingrowth whereas the mesopores are expected to enhance cell attachment onto the structure. In the last stage of this study, the sol-gel-derived 45S5 Bioglass® was surface modified with a silane coupling agent (methacryloxypropyltriethoxysilane) in order to improve its interfacial compatibility with PLA. This process effectively increased the stability of the glass particles in PLA solutions. It also diminished the agglomeration of glass particles. Surface modified glass particles (2 wt.%) were subsequently incorporated into the NIPS foaming process to produce composite foams. It was shown that the particle incorporation route (via solvent or nonsolvent) had the greatest impact on morphology, porosity and crystallinity of the resulting foams. An incorporation of 2 wt.% of particles via nonsolvent significantly decreased the porosity and crystallinity of the PLA matrix. The incorporation of particles via solvent increased the average size of the macropores and made them more homogeneous in terms of size. It also slightly increased the porosity of the foams whereas no impact on the crystallinity of their PLA matrices was observed. SEM examination revealed that the surface modified particles were incorporated within the open mesoporous structure of the foams where they can simultaneously be in contact with the physiological fluids