Neovascularization is critical for bone regeneration. Numerous studies have explored prevascularization preimplant strategies, ranging from calcium phosphate cement (CPC) scaffolds to co-culturing CPCs with stem cells. The aim of the present study was to evaluate an alternative in vivo prevascularization approach, using preimplant-prepared macroporous beta-tricalcium phosphate (β-TCP) scaffolds and subsequent transplantation in bone defect model. The morphology of β-TCPs was characterized by scanning electron microscopy. After 3 weeks of prevascularization within a muscle pouch at the lateral size of rat tibia, we transplanted prevascularized macroporous β-TCPs in segmental tibia defects, using blank β-TCPs as a control. Extent of neovascularization was determined by angiography and immunohistochemical (IHC) evaluations. Tibia samples were collected at different time points for biomechanical, radiological, and histological analyses. RT-PCR and western blotting were used to evaluate angio- and osteo-specific markers. With macroporous β-TCPs, we documented more vascular and supporting tissue invasion in the macroporous β-TCPs with prior in vivo prevascularization. Radiography, biomechanical, IHC, and histological analyses revealed considerably more vascularity and bone consolidation in β-TCP scaffolds that had undergone the prevascularization step compared to the blank β-TCP scaffolds. Moreover, the prevascularization treatment remarkably upregulated mRNA and protein expression of BMP2 and vascular endothelial growth factor (VEGF) during bone regeneration. This novel in vivo prevascularization strategy successfully accelerated vascular formation to bone regeneration. Our findings indicate that prevascularized tissue-engineered bone grafts have promising potential in clinical applications. This study indicates a novel in vivo prevascularization strategy for growing vasculature on β-TCP scaffolds to be used for repair of large segmental bone defects, might serve as a promising tissue-engineered bone grafts in the future.

Aims: The aim of this study was to explore why some calcar screws are malpositioned when a proximal humeral fracture is treated by internal fixation with a locking plate, and to identify risk factors for this phenomenon. Some suggestions can be made of ways to avoid this error. Methods: We retrospectively identified all proximal humeral fractures treated in our institution between October 2016 and October 2018 using the hospital information system. The patients’ medical and radiological data were collected, and we divided potential risk factors into two groups: preoperative factors and intraoperative factors. Preoperative factors included age, sex, height, weight, body mass index, proximal humeral bone mineral density, type of fracture, the condition of the medial hinge, and medial metaphyseal head extension. Intraoperative factors included the grade of surgeon, neck-shaft angle after reduction, humeral head height, restoration of medial support, and quality of reduction. Adjusted binary logistic regression and multivariate logistic regression models were used to identify pre- and intraoperative risk factors. Area under the curve (AUC) analysis was used to evaluate the discriminative ability of the multivariable model. Results: Data from 203 patients (63 males and 140 females) with a mean age of 62 years (22 to 89) were analyzed. In 49 fractures, the calcar screw was considered to be malpositioned; in 154 it was in the optimal position. The rate of malpositioning was therefore 24% (49/203). No preoperative risk factor was found for malpositioning of the calcar screws. Only the neck-shaft angle was found to be related to the risk of screw malpositioning in a multivariate model (with an AUC of 0.72). For the fractures in which the neck-shaft angle was reduced to between 130° and 150°, 91% (133/46) of calcar screws were in the optimal position. Conclusion: The neck-shaft angle is the key factor for the appropriate positioning of calcar screws when treating a proximal humeral fracture with a locking plate. We recommend reducing the angle to between 130° and 150°. Cite this article: Bone Joint J 2020;102-B(12):1629–1635.

Osteocytes are the most abundant cell type in bone. However, the detailed functions of osteocyte subsets in osteoporosis have remained obscure. In this study, it is aimed to investigate the impact of osteocyte subset heterogeneity on the pathological process of osteoporosis and new potential molecular mechanisms. Six osteocyte subsets are identified in mouse bones by single‐cell sequencing. Among them, the epidermal growth factor receptor (Egfr)+ interleukin‐1 receptor type I (Il1r1)+ Semaphorin 5a (Sema5a)+osteocyte subpopulation (bone homeostasis regulatory osteocytes, BHR‐Ocys) played a key role in the maintenance of bone homeostasis by regulating osteoblasts and osteoclasts. The data confirm that the increased proportion of BHR‐Ocys contributes to bone loss in the postmenopausal osteoporotic mice. Mechanistically, Sema5a derived from BHR‐Ocys binds to the osteoclast receptor protein Plexin A1 (Plxna1), thereby activating the phosphatidylinositol‐3 kinase/protein kinase B/myelocytomatosis oncogen (PI3K/AKT/Myc) signaling pathway, leading to active osteoclast‐mediated bone resorption. In conclusion, BHR‐Ocys is a key cell subpopulation in the regulation of bone homeostasis. The Sema5a‐Plxna1 axis is an important mechanism for BHR‐Ocys to regulate osteoclast differentiation. The study provides new insights into the role and mechanism of osteocytes in the regulation of bone homeostasis and identifies new targets for the prevention and treatment of osteoporosis.

Purpose: Segmental tibial diaphyseal bone defects after open fracture are difficult to treat and require timely, coordinated reconstruction. We aimed to develop evidence-based surgical guidelines based on meta-analysis and consensus recommendations from an expert committee of orthopedic surgeons. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, we searched 5 databases (1989 to 2024) for studies evaluating surgical treatment of post-traumatic tibial diaphyseal segmental defects. Random-effects models pooled union rate, union time, and complication rate across 4 techniques (Ilizarov bone transport [IBT], free vascularized bone grafting [FVBG], nonvascularized autografting [AG], and the Masquelet technique [MT]). Consensus recommendations were developed using a Delphi process. Results: Twenty-eight studies, including 824 patients (824 tibias) were analyzed: IBT (11 studies; n=361), FVBG (4; n=68), AG (10; n=164), and MT (6; n=67). Pooled union rates were 96% (IBT), 95% (FVBG), 95% (AG), and 81% (MT). Mean pooled union times were 33.04 weeks (IBT), 37.81 (FVBG), 29.73 (AG), and 29.74 (MT). Pooled complication rates were 82% (IBT), 94% (FVBG), 44% (AG), and 53% (MT). Conclusion: On the basis of the evidence and expert consensus, early operative management with prompt stabilization and antimicrobial therapy, supported by multidisciplinary care, is recommended. For large or complex defects, IBT and FVBG are generally preferred, while AG and MT remain options in selected scenarios. Outcomes depend on early intervention, appropriate technique selection, and structured rehabilitation; further high-quality studies are needed to validate these recommendations.