Soybean Lecithin-Mediated Nanoporous PLGA Microspheres with Highly Entrapped and Controlled Released BMP-2 as a Stem Cell Platform

摘要

Injectable polymer microsphere-based stem cell delivery systems have a severe problem that they do not offer a desirable environment for stem cell adhesion, proliferation, and differentiation because it is difficult to entrap a large number of hydrophilic functional protein molecules into the core of hydrophobic polymer microspheres. In this work, soybean lecithin (SL) is applied to entrap hydrophilic bone morphogenic protein-2 (BMP-2) into nanoporous poly(lactide-co-glycolide) (PLGA)-based microspheres by a two-step method: SL/BMP-2 complexes preparation and PLGA/SL/BMP-2 microsphere preparation. The measurements of their physicochemical properties show that PLGA/SL/BMP-2 microspheres had significantly higher BMP-2 entrapment efficiency and controlled triphasic BMP-2 release behavior compared with PLGA/BMP-2 microspheres. Furthermore, the in vitro and in vivo stem cell behaviors on PLGA/SL/BMP-2 microspheres are analyzed. Compared with PLGA/BMP-2 microspheres, PLGA/SL/BMP-2 microspheres have significantly higher in vitro and in vivo stem cell attachment, proliferation, differentiation, and matrix mineralization abilities. Therefore, injectable nanoporous PLGA/SL/BMP-2 microspheres can be potentially used as a stem cell platform for bone tissue regeneration. In addition, SL can be potentially used to prepare hydrophilic protein-loaded hydrophobic polymer microspheres with highly entrapped and controlled release of proteins.