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.

Background: This study was set to investigate the correlation between square dance and musculoskeletal system of early postmenopausal Chinese women. Methods: Chinese postmenopausal women, who had been without menstruation for 1–10 years from the onset of menopause were recruited from community centers for this study. A standardized structured face-to-face interview was performed to collect demographic information, life styles, personal medical history, diet and menstrual status. Subjects who had been practicing regular square dance without participated in other sports activities for more than 2 years and over 4 h per week (usually more than 45 min per time and more than 5 times per week) were assigned to square dance group. Those postmenopausal women who had not participated in regular exercises (no more than 0.5 h per week) were recruited as the sedentary control group. Bone mineral density (BMD) of spine, total hip and femoral neck was measured by using dual-energy X-ray absorptiometry. Lower limb muscle strength was measured for the non-dominant leg, body flexibility was measured by a simple trunk bend-and-reach test, and body balance was evaluated using a single-stance test for the non-dominant leg. Independent two-tailed Student’s t-test was used for data analysis. Results: 152 subjects from community centers were selected for this study and divided into square dance group (n = 74) and control group (n = 78). The square dance subjects had higher lumbar spine BMD (p = 0.01) and total hip BMD (p = 0.02) than control subjects, but there was no significant difference of femoral neck BMD (p = 0.48) between these two groups. Functional testing indicated that square dance subjects had higher lower limb muscle strength (p < 0.01) and longer single-stance time (p = 0.02) than the control subjects, but there was no significant difference in trunk bend-and-reach (p = 0.12) between these two groups. Conclusion: Our results show that postmenopausal Chinese women can get beneficial effects, like higher BMD, stronger lower limb muscle and improved body balance ability on musculoskeletal system by participating in square dance regularly.