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

Abstract

In osteoporosis and diabetes, it is essential to accelerate the bone repair and regeneration process. Trace rare earth elements such as lanthanum (La) ions (La3+) 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 La3+ 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 La3+ storage and release systems for osteogenesis. So far, there is no study about microsphere-based scaffolds to release trace La3+ 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 La3+ 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 La3+ 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 La3+ could effectively improve osteogenic performance, which provides a new idea for the construction of bone tissue engineering scaffolds.

Systematic review of the osteogenic effect of rare earth nanomaterials and the underlying mechanisms

“…Due to the concentration-dependent effects of RE NMs on osteogenesis, the controlled release of RE NPs or RE ions is a challenge that must be considered when designing rare earth-doped materials. Xu [ 202 ] developed poly(lactide coglycolide) (PLGA)-based microsphere-based 3D porous scaffolds as La 3+ storage and release systems to promote osteogenesis. RE NMs with sustained release properties are ideal bone implant materials.…”

“…Previous studies have employed various methods to mitigate toxicity, including the design of biocomposite materials with sustained release properties [ 202 ] or of RE NMs coated with other materials [ 227 ]. For instance, PLGA-based microsphere-incorporated La-doped 3D porous scaffolds has demonstrated slow-release properties of La 3+ , reducing the toxicity of scaffolds and remaining within a safe range for 28 days [ 202 ]. Increasing the crystallinity of RE NMs can serve as an alternative approach for sustained release of RE ions [ 8 ].…”

On membrane-based approaches for rare earths separation and extraction – Recent developments

“…Although REEs are broadly applied in the biomedical sectors, e.g., bioimaging, sensing, photothermal and photodynamic therapy [308,309], drug delivery [310,311], and optogenetics [312,313], their extensive utilization and high demand have raised concerns about their safety.…”

The Effect of Lanthanum (III) Nitrate on the Osteogenic Differentiation of Mice Bone Marrow Stromal Cells

“…Liu et al [ 13 ] found that lanthanum chloride (LaCl 3 ) has two opposing effects on the proliferation, osteogenic differentiation, and mineralisation of MC3T3-E1 cells, significantly increasing these processes at lower concentrations and inhibiting the processes at higher concentrations. Elsewhere, Xu et al [ 14 ] reported that La 3+ inhibits the differentiation of bone marrow stromal cells (BMSCs) into osteoblasts in the early stage via activation of a mitogen-activated protein kinase signalling pathway, while Jiang et al [ 15 ] demonstrated that LaCl 3 inhibits osteoclast formation, function and osteoclast-specific gene expression in vitro. However, the absorbed La may form precipitates in biological systems [ 14 , 16 ].…”

“…Elsewhere, Xu et al [ 14 ] reported that La 3+ inhibits the differentiation of bone marrow stromal cells (BMSCs) into osteoblasts in the early stage via activation of a mitogen-activated protein kinase signalling pathway, while Jiang et al [ 15 ] demonstrated that LaCl 3 inhibits osteoclast formation, function and osteoclast-specific gene expression in vitro. However, the absorbed La may form precipitates in biological systems [ 14 , 16 ]. While the effects of La 3+ on bone cells have been previously reported, the biological effects of La-containing precipitates are not well understood [ 14 ].…”