Storage and release of rare earth elements in microsphere-based scaffolds for enhancing osteogenesis

In osteoporosis and diabetes, it is essential to accelerate the bone repair and regeneration process. Trace rare earth elements such as lanthanum (La) ions (La 3+ ) with appropriate concentrations are bioactive and can effectively regulate bone tissue performances. However, few well-established bone tissue engineering scaffolds can precisely and stably release La 3+ to promote bone regeneration significantly. Based on the advantages of biodegradable microspheres and microsphere-based scaffolds for controlled drug release, we developed poly(lactide-co-glycolide) (PLGA)-based microsphere-based scaffolds as both three-dimensional (3D) porous scaffolds and La 3+ storage and release systems for osteogenesis. So far, there is no study about microsphere-based scaffolds to release trace La 3+ to induce osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs). PLGA microspheres co-embedded with La-doped mesoporous silica (LMS) with different amounts of doped La were sintered to prepare the LMS/PLGA (LMSP) microsphere-based scaffold. The La 3+ release behavior of LMSP can be controlled by adjusting the doping amount of La in mesoporous silica (MS). All these scaffolds possessed a 3D network architecture. With the increase of La doping, LMSP can better compensate for the pH decrease caused by PLGA degradation. The combination of MS and PLGA can avoid the cytotoxicity of MS alone. All prepared LMSP scaffolds were non-cytotoxic. After BMSCs were implanted on scaffolds, LMSP could promote cells adhesion, proliferation, and osteogenic differentiation. Among these microsphere-based scaffolds, LMSP-3 with stable and higher dose La 3+ release behavior showed the strongest ability to enhance the osteogenesis of BMSCs. The results showed that microsphere-based scaffolds with the ability to store and stably control the release of La 3+ could effectively improve osteogenic performance, which provides a new idea for the construction of bone tissue engineering scaffolds.