No 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.

The etiology of osteonecrosis of the femoral head (ONFH) is not yet fully understood. However, ONFH is a common disease with high morbidity, and approximately one-third of cases are caused by glucocorticoids. We performed single-cell RNA sequencing of bone marrow to explore the effect of glucocorticoid on ONFH. Bone marrow samples of the proximal femur were extracted from four participants during total hip arthroplasty, including two participants diagnosed with ONFH for systemic lupus erythematosus (SLE) treated with glucocorticoids (the case group) and two participants with femoral neck fracture (the control group). Unbiased transcriptome-wide single-cell RNA sequencing analysis and computational analyses were performed. Seventeen molecularly defined cell types were identified in the studied samples, including significantly dysregulated neutrophils and B cells in the case group. Additionally, fatty acid synthesis and aerobic oxidation were repressed, while fatty acid beta-oxidation was enhanced. Our results also preliminarily clarified the roles of the inflammatory response, substance metabolism, vascular injury, angiogenesis, cell proliferation, apoptosis, and dysregulated coagulation and fibrinolysis in glucocorticoid-induced ONFH. Notably, we list the pathways that were markedly altered in glucocorticoid-induced ONFH with SLE compared with femoral head fracture, as well as their common genes, which are potential early therapeutic targets. Our results provide new insights into the mechanism of glucocorticoid-induced ONFH and present potential clues for effective and functional manipulation of human glucocorticoid-induced ONFH, which could improve patient outcomes.