Controlled formation of highly porous polylactic acid‑calcium phosphate granules with defined structure

Synthetic bone repair materials are becoming increasingly popular in tissue engineering as a replacement for autografts and human/animal-based bone grafts. The biomedical application requires precise control over the material composition and structure, as well as over the size of granulate used for filling the bone defects, as the pore size and interconnectivity affect the regeneration process. This paper proposes a process of alloplastic and biodegradable polylactic acid/β-tricalcium phosphate granulates preparation and its parameters described. Using solvent-induced phase separation technique, porous spheres have been obtained in various sizes and morphologies. The design of the experiment's approach generated an experimental plan for further statistical modeling using the resulting data. The statistical modeling approach to the data from conducting a designed set of experiments allowed analysis of the influence of process parameters on the properties of the resulting granules. We confirmed that the content of β-tricalcium phosphate plays the most significant role in the size distribution of prepared granulate. The shape of the particles becomes less spherical with higher phosphate concentration in the emulsion. The proposed technique allows preparing porous granulates in the 0.2-1.8 mm diameter range, where granules' mean diameter and sphericity are tunable with polymer and phosphate concentrations. The granulate created a potentially implantable scaffold for resected bone regeneration, as cytotoxicity tests assured the material is non-cytotoxic in vitro, and human mesenchymal stem cells have been cultured on the surface of granulates. Results from cell cultures seeded on the Resomer LR 706S granulates were the most promising.