Layered Double Hydroxide Modified Bone Cement Promoting Osseointegration via Multiple Osteogenic Signal Pathways

Abstract

Poly(methyl methacrylate) (PMMA) bone cement has been widely used in orthopedic surgeries including total hip/knee replacement, vertebral compression fracture treatment, and bone defect filling. However, aseptic loosening of the interface between PMMA bone cement and bone often leads to failure. Hence, the development of modified PMMA that facilitates the growth of bone into the modified PMMA bone cement is key to reducing the incidence of aseptic loosening. In this study, MgAl-layered double hydroxide (LDH) microsheets modified PMMA (PMMA&LDH) bone cement with superior osseointegration performance has been synthesized. The maximum polymerization reaction temperature of PMMA&LDH decreased by 7.0 and 11.8 °C, respectively, compared with that of PMMA and PMMA&COL-I (mineralized collagen I modified PMMA). The mechanical performance of PMMA&LDH decreased slightly in comparison with PMMA, which is beneficial to alleviate stress-shielding osteolysis, and indirectly promote osseointegration. The superior osteogenic ability of PMMA&LDH has been demonstrated in vivo, which boosts bone growth by 2.17-and 18.34-fold increments compared to the PMMA&COL-I and PMMA groups at 2 months, postoperatively. Moreover, transcriptome sequencing revealed four key osteogenic pathways: p38 MAPK, ERK/MAPK, FGF, and TGF-β, which were further confirmed by IPA, qPCR, and Western blot assays. Hence, LDH-modified PMMA bone cement is a promising biomaterial to enhance bone growth with potential applications in relevant orthopedic surgeries.

In situ construction of flower-like nanostructured calcium silicate bioceramics for enhancing bone regeneration mediated via FAK/p38 signaling pathway

“…In addition, the results in Fig. 7 c, d demonstrated that the expression levels of p-FAK and p-p38 in the nCS group were both decreased in the presence of specific inhibitors, as demonstrated by Western blotting and the subsequent quantitative analysis, indicating that flower-like nanostructures could activate p-FAK and furthermore activated p-p38, which played a crucial role in osteogenesis [ 54 ]. Considering these results together with the qRT–PCR results, we believe that flower-like nanostructures could enhance cell adhesion and osteogenic differentiation mainly by activating the FAK/p38 signaling pathway.…”

Engineered bone cement trigger bone defect regeneration

“…This modification not only reduced the damage caused by PMMA to osteoblasts due to high polymerization temperature but also released magnesium ions to promote osteogenesis. In addition, the microsphere structure on the surface after lactate dehydrogenase degradation was also beneficial for bone formation (Figure 1) (Wang et al, 2021). In addition, Sharma et al improved PMMA bone cement with amine group-functionalized graphene, which reduced cytotoxicity and improved the toughness of bone cement.…”

“…An increased ratio of P-p38 to p38 indicates the activation of the p38 MAPK signaling pathway. Reproduced with permission from(Wang et al, 2021).…”

Precision medicine strategies for spinal degenerative diseases: Injectable biomaterials with in situ repair and regeneration

“…added the active metal component Mg–Al layered double hydroxide (LDH) into PMMA. The micro-CT 3D reconstruction showed that after 2 months surgery the volume of new bone was 2.17- and 18.34-fold greater than that of the PMMA&Collagen-I and PMMA groups, respectively, and its role in inducing bone regeneration was further confirmed by assessing key osteogenic pathways [ 85 ]. Yang et al.…”