The treatment of large bone defects remains a significant clinical challenge due to the limitations of current grafting techniques, including donor site morbidity, restricted availability, and suboptimal integration. Recent advances in 3D bioprinting technology have enabled the fabrication of structurally and functionally optimized scaffolds that closely mimic native bone tissue architecture. This review comprehensively examines the latest developments in 3D-printed scaffolds for bone regeneration, focusing on three critical aspects: (1) material selection and composite design encompassing metallic; (2) structural optimization with hierarchical porosity (macro/micro/nano-scale) and biomechanical properties tailored; (3) biological functionalization through growth factor delivery, cell seeding strategies and surface modifications. We critically analyze scaffold performance metrics from different research applications, while discussing current translational barriers, including vascular network establishment, mechanical stability under load-bearing conditions, and manufacturing scalability. The review concludes with a forward-looking perspective on innovative approaches such as 4D dynamic scaffolds, smart biomaterials with stimuli-responsive properties, and the integration of artificial intelligence for patient-specific design optimization. These technological advancements collectively offer unprecedented opportunities to address unmet clinical needs in complex bone reconstruction.

Aims: To investigate the effects of senescent osteocytes on bone homeostasis in the progress of age-related osteoporosis and explore the underlying mechanism.Methods: In a series of in vitro experiments, we used tert-Butyl hydroperoxide (TBHP) to induce senescence of MLO-Y4 cells successfully, and collected conditioned medium (CM) and senescent MLO-Y4 cell-derived exosomes, which were then applied to MC3T3-E1 cells, separately, to evaluate their effects on osteogenic differentiation. Furthermore, we identified differentially expressed microRNAs (miRNAs) between exosomes from senescent and normal MLO-Y4 cells by high-throughput RNA sequencing. Based on the key miRNAs that were discovered, the underlying mechanism by which senescent osteocytes regulate osteogenic differentiation was explored. Lastly, in the in vivo experiments, the effects of senescent MLO-Y4 cell-derived exosomes on age-related bone loss were evaluated in male SAMP6 mice, which excluded the effects of oestrogen, and the underlying mechanism was confirmed.Results: The CM and exosomes collected from senescent MLO-Y4 cells inhibited osteogenic differentiation of MC3T3-E1 cells. RNA sequencing detected significantly lower expression of miR-494-3p in senescent MLO-Y4 cell-derived exosomes compared with normal exosomes. The upregulation of exosomal miR-494-3p by miRNA mimics attenuated the effects of senescent MLO-Y4 cell-derived exosomes on osteogenic differentiation. Luciferase reporter assay demonstrated that miR-494-3p targeted phosphatase and tensin homolog (PTEN), which is a negative regulator of the phosphoinositide 3-kinase (PI3K)/AKT pathway. Overexpression of PTEN or inhibition of the PI3K/AKT pathway blocked the functions of exosomal miR-494-3p. In SAMP6 mice, senescent MLO-Y4 cell-derived exosomes accelerated bone loss, which was rescued by upregulation of exosomal miR-494-3p.Conclusion: Reduced expression of miR-494-3p in senescent osteocyte-derived exosomes inhibits osteogenic differentiation and accelerates age-related bone loss via PTEN/PI3K/AKT pathway.Cite this article: Bone Joint Res 2024;13(2):52–65.

Purpose: In this study, we aimed to investigate the effects of postoperative malrotation alignment on the outcomes of Gartland type III/IV paediatric supracondylar humeral fracture (SCHF) treated by close reduction and percutaneous K-wire fixation. Methods: Between January 2014 and December 2021, 295 Gartland type III/IV paediatric SCHFs treated by close reduction and percutaneous K-wire fixation were selected for this retrospective study. The demographic, clinical and radiographic parameters of all cases were collected. The lateral rotation percentage (LRP) was measured on X-rays to evaluate postoperative malrotation alignment of the fracture. All cases were categorized into 4 groups according to LRP: LRP ≤ 10% (210, 71.2%), 10% < LRP ≤ 20% (41, 13.9%), 20% < LRP ≤ 30% (26, 8.8%) and LRP > 30% (18, 6.1%). The carrying angle, ranges of multidirectional motions, Mayo Elbow Performance Score (MEPS) and Flynn’s Standard Score (FSS) of the injured elbow were assessed 6 months postoperation and compared among different groups. ROC analysis based on LRP and the excellent/good rate of FSS was performed to determine the acceptable maximum degree of postoperative malrotation alignment. Results: There was no difference in the demographic characteristics (age, sex, injured side and fracture type), postoperative Baumann angle, carrying angle or range of forearm rotation among the 4 groups (P > 0.05). The operation time and time from operation to K-wire removal were longer in the 20% < LRP ≤ 30% and LRP > 30% groups than in the LRP < 10% and 10% < LRP ≤ 20% groups (P < 0.001). The shaft condylar angle, range of elbow flexion, MEPS and FSS of the injured elbow 6 months postoperatively were lower in the 20% < LRP ≤ 30% and LRP > 30% groups than in the LRP < 10% and 10% < LRP ≤ 20% groups (P < 0.001). ROC analysis based on LRP and the excellent/good rate of FSS showed an area under the curve of 0.959 (95% CI 0.936–0.983), with a cutoff value of 26.5%, sensitivity of 95.3% and specificity of 90.1%. Conclusion: A certain degree of residual malrotation alignment deformity of the SCHF may reduce the shaft condylar angle and extend the time from operation to removing the K-wire and affect elbow function, especially the range of elbow flexion. The acceptable maximum degree of residual malrotation deformity expressed as the LRP value was 26.5%.